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Hostiuc M, Negoi I. Etiology and Risk Factors for Splanchnic Vein Thrombosis in Non-Cirrhotic, Non-Neoplastic Patients: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:933. [PMID: 40428892 PMCID: PMC12113251 DOI: 10.3390/medicina61050933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/18/2025] [Revised: 05/13/2025] [Accepted: 05/19/2025] [Indexed: 05/29/2025]
Abstract
Splanchnic vein thrombosis (SVT) is a heterogeneous group of disorders affecting the portal, mesenteric, splenic, and hepatic veins. While frequently associated with liver cirrhosis and malignancy, SVT also occurs in non-cirrhotic, non-neoplastic patients. This narrative review evaluates the epidemiology and risk factors for SVT in this population. The prevalence and incidence of SVT in non-cirrhotic, non-neoplastic patients remain incompletely characterized, with estimates varying widely across studies. The clinical significance of SVT relates to potential complications, including intestinal ischemia, portal hypertension, and a possible underlying systemic disorder. Risk factors for SVT can be categorized into local abdominal conditions, thrombophilias, and systemic disorders. Local factors include inflammatory bowel disease, pancreatitis, abdominal surgery, and trauma. Thrombophilias, both inherited and acquired, are significant contributors to SVT risk. Systemic conditions associated with SVT include autoimmune disorders, pregnancy, hematological diseases, and infections. The complex interplay of these risk factors highlights the need for a comprehensive evaluation of SVT patients. Early recognition and management of these conditions can prevent potentially life-threatening complications and guide decisions regarding anticoagulation and long-term follow-up.
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Affiliation(s)
- Mihaela Hostiuc
- Internal Medicine, Department 5, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ionut Negoi
- General Surgery, Department 10, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
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Leon G, Klavina PA, Rehill AM, Cooper SEJ, Dominik A, Basavarajappa SC, O'Donnell JS, Hussey S, Walsh PT, Preston RJS. Tissue factor-dependent colitogenic CD4 + T cell thrombogenicity is regulated by activated protein C signalling. Nat Commun 2025; 16:1677. [PMID: 39956825 PMCID: PMC11830781 DOI: 10.1038/s41467-025-57001-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 02/07/2025] [Indexed: 02/18/2025] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE), but the underlying mechanistic basis remains poorly defined. Here, we find that colitogenic CD4+ T cells express tissue factor (TF) and promote rapid TF-dependent plasma thrombin generation. TF+CD3+CD4+ T cells are present in both the colons of mice with experimental colitis and blood and colonic tissue from patients with IBD. Expression of genes involved in regulating coagulation, including Protein C (PC; encoded by PROC) and its receptor (PROCR), are dysregulated in IBD patient gut biopsy tissues. Moreover, activated PC signalling reduces the procoagulant activity mediated by TF+CD4+ T cells. Our data thus identify TF-induced, colitogenic T cell-mediated thrombogenicity, and also demonstrate a new function for activated PC signalling in regulating T cell thrombo-inflammatory activity.
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Affiliation(s)
- Gemma Leon
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Paula A Klavina
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Aisling M Rehill
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Sarah E J Cooper
- National Centre for Paediatric Gastroenterology, CHI-Crumlin, Dublin, Ireland
| | - Anna Dominik
- National Centre for Paediatric Gastroenterology, CHI-Crumlin, Dublin, Ireland
| | | | - James S O'Donnell
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Seamus Hussey
- National Centre for Paediatric Gastroenterology, CHI-Crumlin, Dublin, Ireland
| | - Patrick T Walsh
- Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Roger J S Preston
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
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Liang F, Ren W, Chao M, Cheng RD, Ren JJ. Multimorbidity and Venous Thromboembolism: Epidemiological Evidence, Pathophysiology, Prophylactic and Therapeutic Anticoagulation Efficacy, Safety, and Difficulties. A Review. Clin Appl Thromb Hemost 2025; 31:10760296251333786. [PMID: 40232191 PMCID: PMC12035268 DOI: 10.1177/10760296251333786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 03/24/2025] [Accepted: 03/24/2025] [Indexed: 04/16/2025] Open
Abstract
Multimorbidity defined as the co-occurrence of two or more chronic comorbidities, is becoming increasingly burdensome and is a big challenge for healthcare systems all over the world. Venous thromboembolism (VTE) is a potentially lethal disease and is the third most common cardiovascular disease. Multimorbidity is closely associated with VTE, and the VTE risk is approximately fourfold higher in individuals with multimorbidity compared to those without. Notable and consistent evidences show a significant association between multimorbidity and VTE. Plausible mechanisms for the observed associations between multimorbidity and VTE have been outlined, including higher prevalence of identified VTE risk factors, organ function and coagulation function disorders, reduced physical activity, older age, low cognitive level of VTE, and complications following the multimorbidity. Worse therapeutic and prophylactic anticoagulation efficacy, and safety are suggested by the studies, and the VTE recurrence and bleeding risk are higher in patients with multimorbidity compared to those without. Management of the therapeutic and prophylactic anticoagulation for VTE in patients with multimorbidity is difficult, and a balanced and detailed evaluation of the risks of VTE and bleeding is needed, and antiplatelet medications, increased doses or alternative direct oral anticoagulants (DOACs), thromboelastography (TEG), and physical activity may be helpful.
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Affiliation(s)
- Feng Liang
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou
| | - Wen Ren
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Min Chao
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Rui-Dong Cheng
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou
| | - Jing-Jing Ren
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Aldiabat M, Alhuneafat L, Al Ta'ani O, Altarawneh S, Aleyadeh W, Almuzamil T, Butt A, Alahmad M, Madi MY, Alsabbagh K, Ayoub M, Kilani Y, Alsakarneh S, Jaber F, Alhamdani A. Inflammatory bowel disease and pulmonary embolism: a nationwide perspective. Eur J Gastroenterol Hepatol 2024; 36:1410-1418. [PMID: 39292971 DOI: 10.1097/meg.0000000000002851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/20/2024]
Abstract
OBJECTIVE To examine the characteristics and outcomes of patients with inflammatory bowel disease (IBD) hospitalized with pulmonary embolism (PE). METHODS This cross-sectional observational study analyzed data from the 2016 to 2019 National Inpatient Sample to investigate hospitalizations for PE in the USA, stratified by the presence or absence of IBD. Adult patients were selected using the International Classification of Diseases, Tenth Revision codes for PE, Crohn's disease, and ulcerative colitis. Data on patient demographics, comorbidities, and hospital characteristics were collected. Statistical analysis included univariable and multivariable logistic regression using Stata/BE 17.0, focusing on in-hospital mortality and complications in PE patients with and without IBD. Adjusted odds ratios (aOR) and their corresponding 95% confidence intervals (CI) were calculated when appropriate. RESULTS PE/IBD group was younger (mean age 58.3 vs. 62.7 years; P < 0.001), had a higher proportion of white patients (81.2% vs. 70.9%; P < 0.001), and had a greater prevalence of chronic liver disease (7.54% vs. 6.02%; P = 0.002) when compared to PE/non-IBD patients. The PE/IBD group had lower prevalence rates of coronary artery disease, congestive heart failure, obesity, chronic obstructive pulmonary disease, hypertension, and diabetes. Regarding primary outcomes, there was no significant difference in in-hospital mortality between the two groups (aOR, 0.92; 95% CI, 0.77-1.09; P = 0.355). However, the IBD/PE group had a higher risk of acute kidney injury, sepsis, septic shock, cardiac arrhythmias, and deep vein thrombosis. As for secondary outcomes, PE/IBD patients had more extended hospital stays and higher healthcare costs compared with PE/non-IBD patients. CONCLUSION Hospitalized PE patients with IBD differ demographically and have a different comorbidity profile compared to those without IBD. PE/IBD patients demonstrate greater use of healthcare resources and elevated risk of hospitalization adverse events than PE/non-IBD patients, highlighting the necessity for individualized management approaches in this population.
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Affiliation(s)
- Mohammad Aldiabat
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA
| | - Laith Alhuneafat
- Department of Cardiovascular Disease, University of Minnesota, Minneapolis, MN
| | - Omar Al Ta'ani
- Department of Medicine, Allegheny Health Network, Pittsburgh
| | - Saba Altarawneh
- Division of Gastroenterology, Department of Medicine,The Wright Center for Graduate Medical Education, Scranton, PA
| | - Wesam Aleyadeh
- Department of Medicine, Akron General Hospital, Akron, Ohio
| | | | - Ali Butt
- Department of Medicine, Allegheny Health Network, Pittsburgh
| | - Majd Alahmad
- Department of Medicine, University of Missouri-Columbia, Columbia, Missouri
| | - Mahmoud Y Madi
- Division of Gastroenterology, Department of Medicine, SSM Health Saint Louis University Hospital, St. Louis, Missouri
| | | | - Malek Ayoub
- Department of Medicine, Washington University in St. Louis, St. Louis, Missouri
| | - Yassine Kilani
- Department of Medicine, Lincoln Medical Center/Weill Cornell Medicine, Bronx, New York
| | - Saqr Alsakarneh
- Department of Medicine, University of Missouri Kansas City, Kansas City, Missouri
| | - Fouad Jaber
- Department of Medicine, University of Missouri Kansas City, Kansas City, Missouri
| | - Adee Alhamdani
- Division of Cardiology, Department of Medicine, Marshall University, Huntington, West Virginia, USA
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Wu Y, Shen J. Unraveling the intricacies of neutrophil extracellular traps in inflammatory bowel disease: Pathways, biomarkers, and promising therapies. Cytokine Growth Factor Rev 2024; 80:156-167. [PMID: 39438227 DOI: 10.1016/j.cytogfr.2024.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 10/06/2024] [Indexed: 10/25/2024]
Abstract
The development of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, involves various factors and is characterized by persistent inflammation of the mucosal lining. However, the role of neutrophils in this process remains controversial. Neutrophil extracellular traps (NETs), which consist of chromatin, antimicrobial proteins, and oxidative enzymes, are released by neutrophils to trap pathogens. They are also involved in various immune-mediated and vascular diseases. NETs act as a vital defense mechanisms at the gut-mucosal interface and are frequently exposed to bacterial, viral, and fungal threats. However, they can also contribute to inflammation and worsen imbalances in the gut bacteria. Recent studies have suggested that NETs have a significant impact on IBD development. Previous studies have shown increased levels of NETs in tissue and blood samples from patients with IBD, as well as in experimental colitis mouse models. Therefore, this review discusses how NETs are formed and their role in the pathophysiology of IBD. It discusses how NETs may lead to tissue damage and contribute to IBD-associated complications. Moreover, non-invasive biomarkers are needed to replace invasive procedures such as endoscopy to better evaluate the disease status. Given the crucial role of NETs in IBD progression, this review focuses on potential NET biomarkers that can help predict the evolution of IBD. Furthermore, this review identifies potential therapeutic targets for regulating NET production, which could expand the range of available treatment options for IBD.
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Affiliation(s)
- Yilin Wu
- Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai 200127, China; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Shanghai Institute of Digestive Disease, No.160 PuJian Road, China
| | - Jun Shen
- Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai 200127, China; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Shanghai Institute of Digestive Disease, No.160 PuJian Road, China.
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Drygiannakis I, Valatas V, Filidou E, Tzenaki N, Archontoulaki E, Dovrolis N, Kandilogiannakis L, Kefalogiannis G, Sidiropoulos P, Kolios G, Koutroubakis IE. Low-Grade Activation of the Extrinsic Coagulation Pathway in Patients with Ulcerative Colitis. Dig Dis Sci 2024; 69:3773-3785. [PMID: 39322807 DOI: 10.1007/s10620-024-08640-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 09/06/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP). AIMS To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC). METHODS In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated. RESULTS UC patients had 4- and 3.7- times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (- 0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (- 0.64), albumin (- 0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2-times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (- 0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05. CONCLUSION Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.
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Affiliation(s)
- Ioannis Drygiannakis
- Gastroenterology Research Laboratory, School of Medicine, University of Crete, 71500, Heraklion, Crete, Greece
- Department of Gastroenterology, University Hospital, P.O. BOX 1352, 71110, Heraklion, Crete, Greece
| | - Vassilis Valatas
- Gastroenterology Research Laboratory, School of Medicine, University of Crete, 71500, Heraklion, Crete, Greece
- Department of Gastroenterology, University Hospital, P.O. BOX 1352, 71110, Heraklion, Crete, Greece
| | - Eirini Filidou
- Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100, Alexandroupolis, Greece
| | - Niki Tzenaki
- Gastroenterology Research Laboratory, School of Medicine, University of Crete, 71500, Heraklion, Crete, Greece
| | - Evangelia Archontoulaki
- Gastroenterology Research Laboratory, School of Medicine, University of Crete, 71500, Heraklion, Crete, Greece
| | - Nikolas Dovrolis
- Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100, Alexandroupolis, Greece
| | - Leonidas Kandilogiannakis
- Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100, Alexandroupolis, Greece
| | | | - Prodromos Sidiropoulos
- Laboratory of Rheumatology, Autoimmunity and Inflammation, School of Medicine, University of Crete, 71500, Heraklion, Crete, Greece
| | - George Kolios
- Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100, Alexandroupolis, Greece
| | - Ioannis E Koutroubakis
- Gastroenterology Research Laboratory, School of Medicine, University of Crete, 71500, Heraklion, Crete, Greece.
- Department of Gastroenterology, University Hospital, P.O. BOX 1352, 71110, Heraklion, Crete, Greece.
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7
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Sharma N, Tewatia P, Harvey PR, Kumar A. Controversies in Venous Thromboembolism Risk Assessment in Inflammatory Bowel Disease: A Narrative Review. Diagnostics (Basel) 2024; 14:2112. [PMID: 39410515 PMCID: PMC11476391 DOI: 10.3390/diagnostics14192112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/10/2024] [Accepted: 09/20/2024] [Indexed: 10/20/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract with increasing rates of incidence and prevalence across the world. Complex inflammatory and prothrombotic pathophysiology in IBD makes venous thromboembolism (VTE) a common complication with significant morbidity and mortality. This risk is increased in pregnancy. As we continue to understand the pathogenesis of IBD, this article highlights the continued risk of VTE following discharge, for which there is currently no clear guidance, yet the risk of VTE remains high. Furthermore, we discuss this increased VTE risk in the context of pregnant IBD patients and the relevant current guidelines. Alongside this, medications that are used to manage IBD carry their own thrombotic risk, which clinicians should be aware of. Assessing VTE risks in IBD populations using newer medications should be a focus of future research.
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Affiliation(s)
| | | | - Philip R. Harvey
- Department of Gastroenterology, The Royal Wolverhampton NHS Trust, Wolverhampton WV10 0QP, UK; (N.S.); (P.T.); (A.K.)
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Adolph TE, Meyer M, Jukic A, Tilg H. Heavy arch: from inflammatory bowel diseases to metabolic disorders. Gut 2024; 73:1376-1387. [PMID: 38777571 PMCID: PMC11287632 DOI: 10.1136/gutjnl-2024-331914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 04/16/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Metabolic disorders and inflammatory bowel diseases (IBD) have captured the globe during Westernisation of lifestyle and related dietary habits over the last decades. Both disease entities are characterised by complex and heterogeneous clinical spectra linked to distinct symptoms and organ systems which, on a first glimpse, do not have many commonalities in clinical practice. However, experimental studies indicate a common backbone of inflammatory mechanisms in metabolic diseases and gut inflammation, and emerging clinical evidence suggests an intricate interplay between metabolic disorders and IBD. OBJECTIVE We depict parallels of IBD and metabolic diseases, easily overlooked in clinical routine. DESIGN We provide an overview of the recent literature and discuss implications of metabolic morbidity in patients with IBD for researchers, clinicians and healthcare providers. CONCLUSION The Western lifestyle and diet and related gut microbial perturbation serve as a fuel for metabolic inflammation in and beyond the gut. Metabolic disorders and the metabolic syndrome increasingly affect patients with IBD, with an expected negative impact for both disease entities and risk for complications. This concept implies that tackling the obesity pandemic exerts beneficial effects beyond metabolic health.
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Affiliation(s)
- Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Moritz Meyer
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Almina Jukic
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
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Székely H, Tóth LM, Rancz A, Walter A, Farkas N, Sárközi MD, Váncsa S, Erőss B, Hegyi P, Miheller P. Anti-tumor Necrosis Factor Alpha Versus Corticosteroids: A 3-fold Difference in the Occurrence of Venous Thromboembolism in Inflammatory Bowel Disease－A Systematic Review and Meta-analysis. J Crohns Colitis 2024; 18:773-783. [PMID: 37952112 PMCID: PMC11140625 DOI: 10.1093/ecco-jcc/jjad193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Indexed: 11/14/2023]
Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is complex, and the role of medication is not precisely defined. We aimed to assess the effects of anti-tumor necrosis factor alpha [anti-TNFα] drugs and conventional anti-inflammatory therapy, namely corticosteroids [CS], immunomodulators [IM], and 5-aminosalicylates [5-ASA] on VTE in IBD. METHODS A systematic search was performed in five databases on November 22, 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios [OR] with 95% confidence intervals [CI], using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool. RESULTS The quantitative analysis included 16 observational studies, with data from 91 322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE [proportion: 0.05, CI: 0.02-0.10], than patients treated with CS [proportion: 0.16, CI: 0.07-0.32], with OR = 0.42 [CI: 0.25-0.71]. IMs resulted in similar proportions of VTE compared with biologics [0.05, CI: 0.03-0.10], with OR = 0.94 [CI: 0.67-1.33]. The proportion of patients receiving 5-ASA having VTE was 0.09 [CI: 0.04-0.20], with OR = 1.00 [CI: 0.61-1.62]. CONCLUSIONS Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.
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Affiliation(s)
- Hajnal Székely
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Laura Mária Tóth
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Anett Rancz
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Hematology, Medical School, Semmelweis University, Budapest, Hungary
| | - Anna Walter
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Nelli Farkas
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | | | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Bálint Erőss
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Pál Miheller
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
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10
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Carrascosa JM, Echarri A, Gavín Sebastián O, García de la Peña P, Martínez Pérez O, Ramirez S, Valderrama M, Montoro Álvarez M. Contraceptive Recommendations for Women with Immune-Mediated Inflammatory Diseases: A Delphi Consensus. Adv Ther 2024; 41:1372-1384. [PMID: 38326688 DOI: 10.1007/s12325-023-02779-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/21/2023] [Indexed: 02/09/2024]
Abstract
INTRODUCTION Immune-mediated inflammatory diseases (IMID) are a group of disorders characterized by chronic inflammation caused by an altered immune regulation in targeted organs or systems. IMID itself could have an implied increased risk of venous thromboembolism (VTE) and this risk varies throughout the course of the disease as well as with some contraceptive methods and treatments. The aim of this study was to present some key considerations in relation to contraception in women with IMID. METHODS This was an exploratory study conducted in Spain following the online modified Delphi methodology with two rounds of participation. Four questionnaires were designed for each medical specialty: gastroenterology, rheumatology, dermatology, and gynecology. Each questionnaire was divided in three domains: general recommendations about IMID, specific recommendations, and contraceptive methods for patients with IMID. A 5-point Likert scale measured agreement with each statement, with an 80% agreement threshold. Following the first round, the percentage of each response was calculated for every item. Subsequently, a second round was conducted to reach a consensus on the items for which discrepancies were observed. RESULTS A total of 52 and 50 experts participated in the first and second round, respectively. Participants agreed on the existence of a higher risk of VTE in inflammatory bowel diseases, psoriasis, and rheumatoid arthritis diseases. Regarding recommendations for contraceptive methods in patients with IMID, experts considered the hormonal intrauterine device (IUD) as a first-line contraceptive (80.0%) and low doses of progesterone-only pills if the latter is not recommended (88.0%). Most of the interviewees concurred on the importance of the patients' contraceptive needs during the disease course (98.1%). CONCLUSION Raising awareness and promoting a multidisciplinary relationship among the physicians involved in the therapeutic decisions by considering all the risk factors when prescribing a contraceptive method is important to prevent VTE in women with IMID.
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Affiliation(s)
- José Manuel Carrascosa
- Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, IGTP, Badalona, Spain
| | - Ana Echarri
- Servicio de Digestivo, Complejo Hospitalario Universitario de Ferrol, La Coruña, Spain
| | - Olga Gavín Sebastián
- Servicio de Hematología y Hemoterapia, Hospital Clínico Universitario Lozano Blesa, Saragossa, Spain
| | | | - Oscar Martínez Pérez
- Servicio de Obstetricia y Ginecología, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Susan Ramirez
- Pfizer Medical SLU, Av. de Europa, 20, B, Alcobendas, 28108, Madrid, Spain
| | - Mónica Valderrama
- Pfizer Medical SLU, Av. de Europa, 20, B, Alcobendas, 28108, Madrid, Spain
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11
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Iding AFJ, Limpens TMP, Ten Cate H, Ten Cate-Hoek AJ. Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study. Eur J Intern Med 2024; 120:85-91. [PMID: 37852838 DOI: 10.1016/j.ejim.2023.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/28/2023] [Accepted: 10/12/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND Clinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking. OBJECTIVES We aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment. PATIENTS/METHODS Consecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3-6 months. PTS was diagnosed using the Villalta score after 6-24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study. RESULTS In total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15-2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14-9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04-4.58]). CONCLUSIONS Patients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.
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Affiliation(s)
- Aaron F J Iding
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Thrombosis Expertise Center, Heart+Vascular Center, Maastricht University Medical Center, Maastricht, The Netherlands.
| | - Thibaut M P Limpens
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Hugo Ten Cate
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Thrombosis Expertise Center, Heart+Vascular Center, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Arina J Ten Cate-Hoek
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Thrombosis Expertise Center, Heart+Vascular Center, Maastricht University Medical Center, Maastricht, The Netherlands
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12
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Gordon H, Burisch J, Ellul P, Karmiris K, Katsanos K, Allocca M, Bamias G, Barreiro-de Acosta M, Braithwaite T, Greuter T, Harwood C, Juillerat P, Lobaton T, Müller-Ladner U, Noor N, Pellino G, Savarino E, Schramm C, Soriano A, Michael Stein J, Uzzan M, van Rheenen PF, Vavricka SR, Vecchi M, Zuily S, Kucharzik T. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2024; 18:1-37. [PMID: 37351850 DOI: 10.1093/ecco-jcc/jjad108] [Citation(s) in RCA: 74] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Indexed: 06/24/2023]
Affiliation(s)
- Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, London, Centre for Immunobiology, Blizard Institute, Faculty of Medicine, Barts & The London Medical School, Queen Mary University of London, UK
| | - Johan Burisch
- Gastrounit, medical division, Hvidovre Hospital, University of Copenhagen, Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | | | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Giorgos Bamias
- GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Manuel Barreiro-de Acosta
- University Hospital Santiago De Compostela CHUS, Department of Gastroenterology - IBD Unit, Santiago De Compostela, Spain
| | - Tasanee Braithwaite
- School of Immunology and Microbiology, King's College London, The Medical Eye Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK
| | - Thomas Greuter
- Division of Gastroenterology and Hepatology, GZO - Zurich Regional Health Center, Wetzikon, Division of Gastroenterology and Hepatology, University Hospital Lausanne - CHUV, Lausanne, Switzerland; Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Catherine Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland; Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent; Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus Liebig University Giessen, Bad Nauheim, Germany
| | - Nurulamin Noor
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gianluca Pellino
- Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain; Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Christoph Schramm
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alessandra Soriano
- Gastroenterology Division and IBD Center, Internal Medicine Department, Azienda Unità Sanitaria Locale - IRCCS, 42122 Reggio Emilia, Italy
| | - Jürgen Michael Stein
- Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Frankfurt/Main, Germany
| | - Mathieu Uzzan
- Department of Gastroenterology, Hôpital Henri Mondor, APHP, Créteil, France
| | - Patrick F van Rheenen
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland
| | - Maurizio Vecchi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Stephane Zuily
- Vascular Medicine Division and French Referral Center for Rare Auto-Immune Diseases, Université de Lorraine, INSERM, DCAC and CHRU-Nancy, Nancy, France
| | - Torsten Kucharzik
- Department of Gastroenterology, Lüneburg Hospital, University of Münster, Lüneburg, Germany
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13
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Kyrle PA, Eischer L, Šinkovec H, Gressenberger P, Gary T, Brodmann M, Heinze G, Eichinger S. The Vienna Prediction Model for identifying patients at low risk of recurrent venous thromboembolism: a prospective cohort study. Eur Heart J 2024; 45:45-53. [PMID: 37769352 PMCID: PMC10757868 DOI: 10.1093/eurheartj/ehad618] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 08/16/2023] [Accepted: 09/07/2023] [Indexed: 09/30/2023] Open
Abstract
BACKGROUND AND AIMS Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and guidelines suggest extended-phase anticoagulation. Many patients never experience recurrence but are exposed to bleeding. The aim of this study was to assess the performance of the Vienna Prediction Model (VPM) and to evaluate if the VPM accurately identifies these patients. METHODS In patients with unprovoked VTE, the VPM was performed 3 weeks after anticoagulation withdrawal. Those with a predicted 1-year recurrence risk of ≤5.5% were prospectively followed. Study endpoint was recurrent VTE over 2 years. RESULTS A total of 818 patients received anticoagulation for a median of 3.9 months. 520 patients (65%) had a predicted annual recurrence risk of ≤5.5%. During a median time of 23.9 months, 52 patients had non-fatal recurrence. The recurrence risk was 5.2% [95% confidence interval (CI) 3.2-7.2] at 1 year and 11.2% (95% CI 8.3-14) at 2 years. Model calibration was adequate after 1 year. The VPM underestimated the recurrence risk of patients with a 2-year recurrence rate of >5%. In a post-hoc analysis, the VPM's baseline hazard was recalibrated. Bootstrap validation confirmed an ideal ratio of observed and expected recurrence events. The recurrence risk was highest in men with proximal deep-vein thrombosis or pulmonary embolism and lower in women regardless of the site of incident VTE. CONCLUSIONS In this prospective evaluation of the performance of the VPM, the 1-year rate of recurrence in patients with unprovoked VTE was 5.2%. Recalibration improved identification of patients at low recurrence risk and stratification into distinct low-risk categories.
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Affiliation(s)
- Paul A Kyrle
- Division of Hematology and Hemostasis, Department of Medicine I, Medical University of Vienna, Vienna A-1090, Austria
- Karl Landsteiner Institute of Thrombosis Research, Vienna A-1020, Austria
| | - Lisbeth Eischer
- Division of Hematology and Hemostasis, Department of Medicine I, Medical University of Vienna, Vienna A-1090, Austria
| | - Hana Šinkovec
- Center for Medical Statistics, Informatics and Intelligent Systems, Institute of Clinical Biometrics, Medical University of Vienna, Vienna A-1090, Austria
| | - Paul Gressenberger
- Division of Angiology, Department of Medicine, Medical University of Graz, Graz A-8010, Austria
| | - Thomas Gary
- Division of Angiology, Department of Medicine, Medical University of Graz, Graz A-8010, Austria
| | - Marianne Brodmann
- Division of Angiology, Department of Medicine, Medical University of Graz, Graz A-8010, Austria
| | - Georg Heinze
- Center for Medical Statistics, Informatics and Intelligent Systems, Institute of Clinical Biometrics, Medical University of Vienna, Vienna A-1090, Austria
| | - Sabine Eichinger
- Division of Hematology and Hemostasis, Department of Medicine I, Medical University of Vienna, Vienna A-1090, Austria
- Karl Landsteiner Institute of Thrombosis Research, Vienna A-1020, Austria
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14
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Dhaliwal G, Patrone MV, Bickston SJ. Venous Thromboembolism in Patients with Inflammatory Bowel Disease. J Clin Med 2023; 13:251. [PMID: 38202258 PMCID: PMC10780135 DOI: 10.3390/jcm13010251] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/16/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Patients diagnosed with inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, experience chronic inflammation of the gastrointestinal tract. Those with IBD face a higher risk of developing venous thromboembolism (VTE) compared to individuals without IBD. This escalated risk is associated with various factors, some modifiable and others non-modifiable, with disease activity being the primary concern. Interestingly, Janus Kinase inhibitors approved for the treatment of IBD may be associated with an increased risk of VTE but only in patients that have other underlying risk factors leading to an overall increased VTE risk. Several recognized medical societies have recommended the use of VTE prophylaxis for hospitalized individuals with IBD. The association between VTE and IBD and the need for pharmacologic prophylaxis remains under-recognized. Increased awareness of this complication can hopefully protect patients from a potentially deadly complication.
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Affiliation(s)
- Galvin Dhaliwal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA 23219, USA; (M.V.P.); (S.J.B.)
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15
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Varghese J, Afzalpurkar S, Harindranath S, Giri S. Standard and Extended Thromboprophylaxis in Patients with Inflammatory Bowel Disease: A Literature Review. Euroasian J Hepatogastroenterol 2023; 13:133-141. [DOI: https:/doi.org/10.5005/jp-journals-10018-1401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/13/2025] Open
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16
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Azzam NA, Almutairdi A, Almudaiheem HY, AlAmeel T, Bakkari SA, Alharbi OR, Alenzi KA, AlMolaiki MA, Al-Omari BA, Albarakati RG, Al-Jedai AH, Saadah OI, Almadi MA, Al-Bawardy B, Mosli MH. Saudi consensus guidance for the management of inflammatory bowel disease during pregnancy. Saudi J Gastroenterol 2023:00936815-990000000-00066. [PMID: 38099556 PMCID: PMC11379253 DOI: 10.4103/sjg.sjg_318_23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 11/08/2023] [Indexed: 09/10/2024] Open
Abstract
ABSTRACT The management of inflammatory bowel disease (IBD) in pregnant women is challenging and must be addressed on a patient-by-patient basis. Optimal patient management requires a multidisciplinary team and clear evidence-based recommendations that cater to this subset of patients. In this article, we provide concise guidelines and clinical care pathway for the management of IBD in pregnant women. Our recommendations were developed by a multidisciplinary working group that includes experts from the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacology. All recommendations are based on up-to-date information following an extensive literature review. A total of 23 evidence-based expert opinion recommendations for the management of IBD in pregnant women are herein provided.
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Affiliation(s)
- Nahla A Azzam
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Abdulelah Almutairdi
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Turki AlAmeel
- Department of Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Shakir A Bakkari
- Department of Gastroenterology, King Saud Medical City, Riyadh, Saudi Arabia
| | - Othman R Alharbi
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Khalidah A Alenzi
- Executive Director of Transformation, Planning, and Business Development, Tabuk Health Cluster, Tabuk, Saudi Arabia
| | - Maha A AlMolaiki
- Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Bedor A Al-Omari
- Department of Pharmaceutical Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Rayan G Albarakati
- Department of Obstetrics and Gynecology, Majmaah University, Riyadh, Saudi Arabia
| | - Ahmed H Al-Jedai
- Deputyship of Therapeutic Affairs, Ministry of Health, Riyadh, Saudi Arabia
- Professor, Colleges of Medicine and Pharmacy, Alfaisal University, Riyadh, Saudi Arabia
| | - Omar I Saadah
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Majid A Almadi
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Badr Al-Bawardy
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Mahmoud H Mosli
- Department of Internal Medicine, King Abdulaziz University, Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
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17
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Papa A, Santini P, De Lucia SS, Maresca R, Porfidia A, Pignatelli P, Gasbarrini A, Violi F, Pola R. Gut dysbiosis-related thrombosis in inflammatory bowel disease: Potential disease mechanisms and emerging therapeutic strategies. Thromb Res 2023; 232:77-88. [PMID: 37951044 DOI: 10.1016/j.thromres.2023.11.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 10/23/2023] [Accepted: 11/03/2023] [Indexed: 11/13/2023]
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of developing venous thromboembolic events, which have a considerable impact on morbidity and mortality. Chronic inflammation plays a crucial role in the pathogenesis of thrombotic events in patients with IBD. However, many unresolved questions remain, particularly regarding the mechanisms that determine the persistent inflammatory state independent of disease activity. This review explored the role of gut microbiota dysbiosis and intestinal barrier dysfunction, which are considered distinctive features of IBD, in determining pro-thrombotic tendencies. Gut-derived endotoxemia due to the translocation of bacterial lipopolysaccharides (LPS) from the intestine to the bloodstream and the bacterial metabolite trimethylamine-N-oxide (TMAO) are the most important molecules involved in gut dysbiosis-related thrombosis. The pathogenic prothrombotic pathways linked to LPS and TMAO have been discussed. Finally, we present emerging therapeutic approaches that can help reduce LPS-mediated endotoxemia and TMAO, such as restoring intestinal eubiosis, normalizing intestinal barrier function, and counterbalancing the effects of LPS and TMAO.
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Affiliation(s)
- Alfredo Papa
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy.
| | - Paolo Santini
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy; Thrombosis Clinic, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy
| | - Sara Sofia De Lucia
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy
| | - Rossella Maresca
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy
| | - Angelo Porfidia
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy; Thrombosis Clinic, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy
| | - Pasquale Pignatelli
- Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Mediterranea Cardiocentro-Napoli, Naples, Italy
| | - Antonio Gasbarrini
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy
| | - Francesco Violi
- Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Mediterranea Cardiocentro-Napoli, Naples, Italy
| | - Roberto Pola
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy; Thrombosis Clinic, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy
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18
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Bhardwaj A, Singh A, Midha V, Sood A, Wander GS, Mohan B, Batta A. Cardiovascular implications of inflammatory bowel disease: An updated review. World J Cardiol 2023; 15:553-570. [PMID: 38058397 PMCID: PMC10696203 DOI: 10.4330/wjc.v15.i11.553] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 10/22/2023] [Accepted: 11/08/2023] [Indexed: 11/23/2023] Open
Abstract
Emerging data highlights the heightened risk of atherosclerotic cardiovascular diseases (ASCVD) in patients with chronic inflammatory disorders, particularly those afflicted with inflammatory bowel disease (IBD). This review delves into the epidemiological connections between IBD and ASCVD, elucidating potential underlying mechanisms. Furthermore, it discusses the impact of current IBD treatments on cardiovascular risk. Additionally, the cardiovascular adverse effects of novel small molecule drugs used in moderate-to-severe IBD are investigated, drawing parallels with observations in patients with rheumatoid arthritis. This article aims to comprehensively evaluate the existing evidence supporting these associations. To achieve this, we conducted a meticulous search of PubMed, spanning from inception to August 2023, using a carefully selected set of keywords. The search encompassed topics related to IBD, such as Crohn's disease and ulcerative colitis, as well as ASCVD, including coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, conduction abnormalities, heart blocks, and premature coronary artery disease. This review encompasses various types of literature, including retrospective and prospective cohort studies, clinical trials, meta-analyses, and relevant guidelines, with the objective of providing a comprehensive overview of this critical intersection of inflammatory bowel disease and cardiovascular health.
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Affiliation(s)
- Arshia Bhardwaj
- Department of Gastroenterology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Gurpreet Singh Wander
- Department of Cardiology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Bishav Mohan
- Department of Cardiology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India.
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19
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Menichelli D, Cormaci VM, Marucci S, Franchino G, Del Sole F, Capozza A, Fallarino A, Valeriani E, Violi F, Pignatelli P, Pastori D. Risk of venous thromboembolism in autoimmune diseases: A comprehensive review. Autoimmun Rev 2023; 22:103447. [PMID: 37714419 DOI: 10.1016/j.autrev.2023.103447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/04/2023] [Accepted: 09/12/2023] [Indexed: 09/17/2023]
Abstract
Autoimmune diseases have specific pathophysiologic mechanisms leading to an increased risk of arterial and venous thrombosis. The risk of venous thromboembolism (VTE) varies according to the type and stage of the disease, and to concomitant treatments. In this review, we revise the most common autoimmune disease such as antiphospholipid syndrome, inflammatory myositis, polymyositis and dermatomyositis, rheumatoid arthritis, sarcoidosis, Sjogren syndrome, autoimmune haemolytic anaemia, systemic lupus erythematosus, systemic sclerosis, vasculitis and inflammatory bowel disease. We also provide an overview of pathophysiology responsible for the risk of VTE in each autoimmune disorder, and report current indications to anticoagulant treatment for primary and secondary prevention of VTE.
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Affiliation(s)
- Danilo Menichelli
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy; Department of General Surgery and Surgical Specialty Paride Stefanini, Sapienza University of Rome, 00161 Rome, Italy
| | - Vito Maria Cormaci
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Silvia Marucci
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Giovanni Franchino
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Francesco Del Sole
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Alessandro Capozza
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Alessia Fallarino
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Emanuele Valeriani
- Department of General Surgery and Surgical Specialty Paride Stefanini, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesco Violi
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Pasquale Pignatelli
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Daniele Pastori
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
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20
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Boccatonda A, Balletta M, Vicari S, Hoxha A, Simioni P, Campello E. The Journey Through the Pathogenesis and Treatment of Venous Thromboembolism in Inflammatory Bowel Diseases: A Narrative Review. Semin Thromb Hemost 2023; 49:744-755. [PMID: 36455617 DOI: 10.1055/s-0042-1758869] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract including Crohn's disease and ulcerative colitis, which may result in several extraintestinal complications (∼20-30% of cases), such as increased risk of venous thromboembolism (VTE). The main pathophysiological mechanism of VTE is an inflammation-induced hypercoagulable state, and recent data have shown that endothelial dysregulation due to gut and systemic inflammation may also lead to a prothrombotic state. Several prothrombotic alterations have been described, such as the activation of the coagulation system, platelet abnormalities, and dysregulation of fibrinolysis. Furthermore, the dysregulation of the gut microbiome seems to play a vital role in increasing systemic inflammation and thus inducing a procoagulant state. Our review aims to examine the main correlations between IBD and VTE, the underlying pathophysiology, and current therapeutic options.
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Affiliation(s)
- Andrea Boccatonda
- Department of Internal Medicine, Bentivoglio Hospital, AUSL Bologna, Bologna, Italy
| | - Marco Balletta
- Department of Internal Medicine, Bologna University, Bologna, Italy
| | - Susanna Vicari
- Department of Internal Medicine, Bentivoglio Hospital, AUSL Bologna, Bologna, Italy
| | - Ariela Hoxha
- Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Paolo Simioni
- Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Elena Campello
- Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
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21
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Peric S, Todorovic Z, Zdravkovic N, Gogic A, Simovic S, Grbovic V, Maksic M, Jakovljevic S, Milovanovic O, Zdravkovic N. Treatment of Ulcerative Colitis: Impact on Platelet Aggregation. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1615. [PMID: 37763734 PMCID: PMC10534470 DOI: 10.3390/medicina59091615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 08/14/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023]
Abstract
Background and Objectives: Ulcerative colitis is chronic and/or progressive inflammation of the colorectal mucosa and submucosa and represents one of two major inflammatory bowel diseases. Ulcerative colitis has been associated with increased risk of arteriosus and venous thrombosis. There are numerous factors responsible for this; one of them is platelet activation and aggregation. The objective of our study was to determine if different treatment options for ulcerative colitis have an impact on platelet aggregation. Materials and Methods: This research was a prospective, observational study and included 94 newly diagnosed patients with UC divided into four treatment groups. For all patients, we measured platelet aggregability by using an impedance aggregometry method with a multiplate analyzer before and after treatment with infliximab, adalimumab, vedolizumab and azathioprine. A Paired Samples t test was performed in order to determine the difference in platelet aggregability before and after a certain therapy, since the data followed a normal distribution. Taking into account the impact of some clinical characteristics, multiple linear regression was conducted for the purpose of estimating the effect of therapy on the level of reduction in platelet aggregability. Results: All four drugs significantly reduced platelet aggregability. After we excluded the influence of clinical and endoscopic scores and disease localization on the results, we found that infliximab had the greatest anti-platelet activity. Conclusions: In addition to the well-known traditional risk factors for atherosclerosis, activation and aggregation of platelets play a significant role in the development of arterial thrombosis, and our results suggested that therapy use for the treatment of UC, especially infliximab, can have a great impact on cardiovascular morbidity and mortality by decreasing platelet aggregability.
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Affiliation(s)
- Sasa Peric
- Clinic of Gastroenterology and Hepatology, Military Medical Academy, Crnotravska Street 17, 11000 Belgrade, Serbia;
| | - Zeljko Todorovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia; (S.S.); (M.M.); (N.Z.)
- Clinic for Hematology, University Clinical Center Kragujevac, Zmaj Jovina Street 30, 34000 Kragujevac, Serbia
| | - Nebojsa Zdravkovic
- Department of Medical Statistics and Informatics, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia; (N.Z.); (A.G.)
| | - Andjela Gogic
- Department of Medical Statistics and Informatics, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia; (N.Z.); (A.G.)
| | - Stefan Simovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia; (S.S.); (M.M.); (N.Z.)
- Clinic for Cardiology, University Clinical Center Kragujevac, Zmaj Jovina Street 30, 34000 Kragujevac, Serbia
| | - Vesna Grbovic
- Department of Physical Medicine and Rehabilitation, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia;
- Center for Physical Medicine and Rehabilitation, University Clinical Center Kragujevac, Zmaj Jovina Street 30, 34000 Kragujevac, Serbia
| | - Mladen Maksic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia; (S.S.); (M.M.); (N.Z.)
- Clinic of Gastroenterology and Hepatology, University Clinical Center Kragujevac, Zmaj Jovina Street 30, 34000 Kragujevac, Serbia
| | - Stefan Jakovljevic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia;
- Clinic for Surgery, University Clinical Center Kragujevac, Zmaj Jovina Street 30, 34000 Kragujevac, Serbia
| | - Olivera Milovanovic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia;
| | - Natasa Zdravkovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia; (S.S.); (M.M.); (N.Z.)
- Clinic of Gastroenterology and Hepatology, University Clinical Center Kragujevac, Zmaj Jovina Street 30, 34000 Kragujevac, Serbia
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Massironi S, Pirola L, Mulinacci G, Ciaccio A, Viganò C, Palermo A, Zilli A, Invernizzi P, Danese S. Use of IBD Drugs in Patients With Hepatobiliary Comorbidities: Tips and Tricks. Inflamm Bowel Dis 2023; 29:1477-1487. [PMID: 36040402 DOI: 10.1093/ibd/izac189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Indexed: 12/09/2022]
Abstract
Advanced therapies (biologic agents and small molecules) for inflammatory bowel diseases (IBD) have radically changed the management of these diseases during the last decade. Data about these drugs in patients with hepatic disorders derive mainly from real-life studies, as these conditions often represent an exclusion criterion from pivotal drug developmental trials. However, IBD patients sometimes have concomitant liver diseases. Nonalcoholic fatty liver disease is the most prevalent hepatic comorbidity, whereas viral hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, and hepatic vascular disorders are less frequent. This review aimed at describing the real-life data about the use of advanced therapies for IBD in patients with concomitant hepatobiliary disorders. Hepatitis B virus and hepatitis C virus infections do not represent an absolute contraindication for novel IBD therapeutic agents. Data from the literature suggest a safe hepatobiliary profile of biologic agents and small molecules in the case of nonalcoholic fatty liver disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and portal vein thrombosis. Consequently, although the liver disease does not affect a different therapeutic approach in patients with concomitant IBD and liver disease, a close risk/benefit analysis for each drug should be performed in these patients, especially in cirrhotic patients and in the postliver transplant setting.
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Affiliation(s)
- Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Lorena Pirola
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Giacomo Mulinacci
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Antonio Ciaccio
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Chiara Viganò
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Andrea Palermo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
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Harindranath S, Varghese J, Afzalpurkar S, Giri S. Standard and Extended Thromboprophylaxis in Patients with Inflammatory Bowel Disease: A Literature Review. Euroasian J Hepatogastroenterol 2023; 13:133-141. [PMID: 38222957 PMCID: PMC10785145 DOI: 10.5005/jp-journals-10018-1401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 10/04/2023] [Indexed: 01/16/2024] Open
Abstract
Patients with inflammatory bowel disease (IBD), both Crohn's disease and ulcerative colitis, frequently experience venous thromboembolism (VTE), a potentially fatal consequence. The pathophysiological mechanisms contributing to VTE include inflammation, modifications in coagulation factors, endothelial dysfunction, and platelet activation. Numerous pro-inflammatory cytokines and markers, such as tumor necrosis factor-alpha and interleukin-6, have a significant impact on the thrombotic cascade. Patients with IBD are more likely to suffer VTE for a variety of causes. Exacerbations of preexisting conditions, admission to the hospital, surgical intervention, immobilization, corticosteroid usage, central venous catheterization, and hereditary susceptibility all fit into this category. The mainstay of therapy for VTE in IBD patients includes anticoagulation that is individualized for each patient depending on the thrombosis site, severity, bleeding risk, and interaction with other drugs. In some high-risk IBD patients, such as those having major surgery or hospitalized with severe flare, preventive anticoagulation may play a role. However, the acceptance rate for this recommendation is low. Additionally, there is a subset of patients who would require extended thromboprophylaxis. The majority of the studies that looked into this question consisted of patients in the surgical setting. Emerging data suggest that risk factors other than surgery can also dictate the duration of anticoagulation. While extending anticoagulation in all patients may help reduce VTE-related mortality, identifying these risk factors is important. Hence, the decision to initiate prophylaxis should be individualized, considering the overall thrombotic and bleeding risks. This review explores the relationship between IBD and VTE, including risk factors, epidemiology, and prevention. A multifactorial approach involving aggressive management of underlying inflammation, identification of modifiable risk factors, and judicious use of anticoagulant therapy is essential for reducing the burden of VTE in this vulnerable population. How to cite this article Harindranath S, Varghese J, Afzalpurkar S, et al. Standard and Extended Thromboprophylaxis in Patients with Inflammatory Bowel Disease: A Literature Review. Euroasian J Hepato-Gastroenterol 2023;13(2):133-141.
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Affiliation(s)
- Sidharth Harindranath
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
| | - Jijo Varghese
- Department of Gastroenterology, NS Hospital, Kollam, Kerala, India
| | - Shivaraj Afzalpurkar
- Department of Gastroenterology, Nanjappa Multispecialty Hospital, Davangere, Karnataka, India
| | - Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
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24
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Brondfield MN, Mahadevan U. Inflammatory bowel disease in pregnancy and breastfeeding. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00758-3. [PMID: 37002407 DOI: 10.1038/s41575-023-00758-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 06/19/2023]
Abstract
Inflammatory bowel disease (IBD) has a peak age of diagnosis before the age of 35 years. Concerns about infertility, adverse pregnancy outcomes, and heritability of IBD have influenced decision-making for patients of childbearing age and their care providers. The interplay between the complex physiology in pregnancy and IBD can affect placental development, microbiome composition and responses to therapy. Current evidence has shown that effective disease management, including pre-conception counselling, multidisciplinary care and therapeutic agents to minimize disease activity, can improve pregnancy outcomes. This Review outlines the management of IBD in pregnancy and the safety of IBD therapies, including novel agents, with regard to both maternal and fetal health. The vast majority of IBD therapies can be used with low risk during pregnancy and lactation without substantial effects on neonatal outcomes.
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Affiliation(s)
- Max N Brondfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Uma Mahadevan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
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25
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Jaiswal V, Batra N, Dagar M, Butey S, Huang H, Chia JE, Naz S, Endurance EO, Raj N, Patel S, Maroo D, Ang SP, Hanif M, Mukherjee D, Sarfraz Z, Shrestha AB, Song D. Inflammatory bowel disease and associated cardiovascular disease outcomes: A systematic review. Medicine (Baltimore) 2023; 102:e32775. [PMID: 36820570 PMCID: PMC9907938 DOI: 10.1097/md.0000000000032775] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND There is limited and conflicting data available regarding the cardiovascular disease outcomes associated with inflammatory bowel disease (IBD). OBJECTIVE We aim to perform a systematic review to evaluate the cardiovascular outcomes and mortality associated with IBD patients. METHODS A systematic literature search has been performed on PubMed, Embase, Cochrane, and Scopus from inception till May 2022 without any language restrictions. RESULTS A total of 2,029,941 patients were included in the analysis from 16 studies. The mean age of the patients was 45.6 years. More females were found compared with males (57% vs 43%). The most common risk factors for cardiovascular disease (CVD) included smoking (24.19%) and alcohol (4.60%). The most common comorbidities includes hypertension (30%), diabetes mellitus (14.41%), dyslipidemia (18.42%), previous CVD (22%), and renal disease (10%). Among outcomes, all-cause mortality among IBD patients was 1.66%; ulcerative colitis (UC): 15.92%; and Crohn disease (CD): 0.30%. Myocardial Infarction (MI) among IBD patients were 1.47%, UC: 30.96%; and CD: 34.14%. CVD events among IBD patients were 1.95%. Heart failure events among IBD patients were 5.49%, stroke events among IBD patients were 0.95%, UC: 2.63%, and CD: 2.41%, respectively. CONCLUSION IBD patients are at higher risk for adverse cardiovascular outcomes, especially in women. Although there remains a lack of concrete treatment algorithms and assessment parameters that better characterize IBD risk factors, nutritional modifications and physical activity should be at the forefront of CVD prevention in IBD.
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Affiliation(s)
| | - Nitya Batra
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, MI
| | - Mehak Dagar
- Department of Medicine, Himalayan Institute of Medical Science, Dehradun, India
| | - Swatika Butey
- Department of Medicine, Indira Gandhi Government Medical College, Nagpur, India
| | - Helen Huang
- Royal College of Surgeons in Ireland, University of Medicine and Health Science, Dublin, Ireland
| | - Jia Ee Chia
- Department of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Sidra Naz
- Department of Gastroenterology, MD Anderson Cancer Center, Houston, TX
| | | | - Nishchita Raj
- Department of Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - Srushti Patel
- Department of Medicine, GMERS Medical College, Gandhinagar, India
| | - Dipansha Maroo
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Song Peng Ang
- Division of Internal Medicine, Rutgers Health/Community Medical Center, Toms River, NJ
| | | | - Dattatreya Mukherjee
- Department of Medicine, Raiganj Government Medical College and Hospital, Raiganj, India
| | - Zouina Sarfraz
- Research and Publication, Fatima Jinnah Medical University, Lahore, Pakistan
| | - Abhigan Babu Shrestha
- M Abdur Rahim Medical College, Dinajpur, Bangladesh
- * Correspondence: Vikash Jaiswal, JCCR Cardiology Research, Varanasi 221005, India (e-mail: )
| | - David Song
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
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Sahyoun L, Dahiya DS, Cheng CI, Sultan K. Letter: fighting the battle but losing the war-inflammatory bowel disease and venous thromboembolism. Aliment Pharmacol Ther 2022; 56:1425-1426. [PMID: 36221159 DOI: 10.1111/apt.17203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
LINKED CONTENTThis article is linked to Faye et al papers. To view these articles, visit https://doi.org/10.1111/apt.17162 and https://doi.org/10.1111/apt.17227
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Affiliation(s)
- Laura Sahyoun
- Department of Digestive Diseases, Yale-New Haven Hospital, New Haven, Connecticut, USA
| | - Dushyant Singh Dahiya
- Department of Internal Medicine, Central Michigan University College of Medicine East Campus, Mount Pleasant, Michigan, USA
| | - Chin-I Cheng
- Department of Statistics, Actuarial, and Data Science, Central Michigan University, Mount Pleasant, Michigan, USA
| | - Keith Sultan
- Zucker School of Medicine at Hofstra/Northwell, Division of Gastroenterology, North Shore University Hospital, Manhasset, and Long Island Jewish Medical Center, Queens, New York, USA
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Ma J, Wang Y, Cao H. When Neurology Meets Gastroenterology: An Unusual Case of Ulcerative Colitis. Gastroenterology 2022; 163:e12-e13. [PMID: 35489431 DOI: 10.1053/j.gastro.2022.04.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/08/2022] [Accepted: 04/21/2022] [Indexed: 12/02/2022]
Affiliation(s)
- Jiahui Ma
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yue Wang
- Department of Neurology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
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Gala D, Newsome T, Roberson N, Lee SM, Thekkanal M, Shah M, Kumar V, Bandaru P, Gayam V. Thromboembolic Events in Patients with Inflammatory Bowel Disease: A Comprehensive Overview. Diseases 2022; 10:diseases10040073. [PMID: 36278572 PMCID: PMC9589934 DOI: 10.3390/diseases10040073] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/22/2022] [Accepted: 09/27/2022] [Indexed: 11/24/2022] Open
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis are chronic inflammatory disorders of the intestines. The underlying inflammation activates the coagulation cascade leading to an increased risk of developing arterial and venous thromboembolic events such as deep vein thrombosis and pulmonary embolism. Patients with IBD are at a 2–3-fold increased risk of developing thromboembolism. This risk increases in patients with active IBD disease, flare-ups, surgery, steroid treatment, and hospitalization. These complications are associated with significant morbidity and mortality making them important in clinical practice. Clinicians should consider the increased risk of thromboembolic events in patients with IBD and manage them with appropriate prophylaxis based on the risk. In this review, we discuss the literature associated with the pathophysiology of thromboembolism in patients with IBD, summarize the studies describing the various thromboembolic events, and the management of thromboembolism in patients with IBD.
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Affiliation(s)
- Dhir Gala
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
- Correspondence:
| | - Taylor Newsome
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Nicole Roberson
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Soo Min Lee
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Marvel Thekkanal
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Mili Shah
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Vikash Kumar
- Department of Internal Medicine, The Brooklyn Hospital Center, 121 DeKalb Ave, Brooklyn, NY 11201, USA
| | - Praneeth Bandaru
- Department of Gastroenterology, The Brooklyn Hospital Center, 121 DeKalb Ave, Brooklyn, NY 11201, USA
| | - Vijay Gayam
- Department of Gastroenterology, The Brooklyn Hospital Center, 121 DeKalb Ave, Brooklyn, NY 11201, USA
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Incidence and impact of venous thromboembolism in hospitalized patients with Crohn's disease. Thromb Res 2022; 219:77-85. [PMID: 36137330 DOI: 10.1016/j.thromres.2022.09.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 09/06/2022] [Accepted: 09/12/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND Crohn's disease (CD) is associated with an increased risk for venous thromboembolism (VTE). Beside higher VTE risk, data on impact of VTE on survival and risk factors for the occurrence of VTE in CD are sparse. METHODS The German nationwide inpatient sample was screened for patients admitted due to CD (ICD-code K50). CD hospitalizations were stratified for VTE and risk-factors for VTE and impact of VTE on in-hospital case-fatality rate were investigated. RESULTS Overall, 333,975 hospitalizations of patients due to CD were counted in Germany (median age 38.0 [IQR 24.0-52.0] years, 56.0 % females) during the observational period 2005-2018. VTE rate increased slightly from 0.6 % (2005) to 0.7 % (2018) (β 0.000097 [95%CI 0.000027 to 0.000167], P = 0.007) 2005-2018 and with age-decade (β 0.0017 [95%CI 0.0016 to 0.0019], P < 0.001). In total, 0.7 % (2295) of the CD inpatients had a VTE event. Patients with VTE were in median 12 years older (49.0 [34.0-62.0] vs. 37.0 [24.0-52.0] years, P < 0.001) and colon-involvement was in those patients more prevalent (32.0 % vs.27.7 %, P < 0.001). Age ≥ 70 years, obesity, colon-involvement, cancer, surgery, thrombophilia, and heart failure were strongly associated with higher risk of VTE in CD patients. In-hospital death occurred 15-times more often in CD with VTE than without (4.5 % vs. 0.3 %, P < 0.001). VTE was independently associated with increased in-hospital case-fatality rate (OR 9.31 [95%CI 7.54-11.50], P < 0.001). CONCLUSIONS VTE is a life-threatening event in hospitalized CD patients associated with 9.3-fold increased case-fatality rate. Older age, obesity, colon involvement, cancer, surgery, thrombophilia and heart failure were strong risk factors for VTE in CD.
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30
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Al Sharie AH, Al Zu'bi YO, Al-Sweedan S, Khasawneh RA, Altamimi E. Successful management of dural venous sinus thrombosis secondary to ulcerative colitis in a pediatric patient: A case report. Radiol Case Rep 2022; 17:2162-2166. [PMID: 35479968 PMCID: PMC9036061 DOI: 10.1016/j.radcr.2022.03.049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 03/11/2022] [Accepted: 03/12/2022] [Indexed: 11/19/2022] Open
Abstract
Cerebral venous sinus thrombosis secondary to inflammatory bowel disease is a clinically rare and challenging entity with serious sequela. We preset a case of a 15-year-old female patient who was recently diagnosed with ulcerative colitis and had been suffering from headache for 4 days duration. During the diagnostic workup, computed tomography (CT) venography revealed Dural venous sinus thrombosis in the left transverse sinus extending into the left sigmoid sinus and the upper third of the left internal jugular vein as well as into the sinus confluence with non–occlusive filling defects in the superior sagittal sinus. Anticoagulant therapy with enoxaparin was initiated and the patient is being monitored in an outpatient setting regularly. Post-discharge disease course was uneventful. CT venography performed after 3 months illustrated partial recanalization of both left transverse and sigmoid sinuses. CVST is a rare extraintestinal manifestation of ulcerative colitis with significant morbidity and mortality which requires a high level of suspicion to establish a clear diagnosis. In spite the fact that CVST is rare, it should be ruled out in inflammatory bowel disease patients with new onset seizures, headache, along with focal, and non–focal neurologic symptoms.
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Affiliation(s)
- Ahmed H. Al Sharie
- Faculty of Medicine, Jordan University of Science & Technology, Irbid 22110, Jordan
| | - Yazan O. Al Zu'bi
- Faculty of Medicine, Jordan University of Science & Technology, Irbid 22110, Jordan
| | - Suleimman Al-Sweedan
- Department of Pediatric, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Ruba A. Khasawneh
- Department of Diagnostic Radiology and Nuclear Medicine, Faculty of Medicine, Jordan University of Science & Technology, Irbid 22110, Jordan
| | - Eyad Altamimi
- Department of Pediatric, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
- Corresponding author.
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Carvalho AC, Pinho J, Cancela E, Vieira HM, Silva A, Ministro P. Inflammatory bowel disease and thromboembolic events: a c'lot to learn. Therap Adv Gastroenterol 2022; 15:17562848221100626. [PMID: 35651649 PMCID: PMC9149613 DOI: 10.1177/17562848221100626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 04/27/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is associated with a variety of extraintestinal manifestations including arterial and venous thromboembolism. Research evidences that IBD patients have about a 2- to 3-fold increase in the risk of venous thromboembolism when compared with the general population. OBJECTIVES We intended to evaluate the coagulation parameters and the prevalence of thromboembolic events (TE) in IBD patients. It was also our aim to investigate the correlation between coagulation parameters and disease phenotype and activity in this population. METHODS This single center prospective observational study was performed between November 2016 and April 2020. The cohort included patients with 18 years of age or older, diagnosed with IBD and followed at a gastroenterology consultation, during a follow-up period of 36 months. Patients were evaluated in terms of IBD type, extent and disease behavior, clinical scores of IBD activity, medication, smoking history, family and personal history of TE, coagulation parameters, fecal calprotectin levels, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hospitalization due to TE, IBD-related hospitalization or surgery, pregnancy, or diagnosis of malignancy. RESULTS The study included 149 IBD patients (67 males and 82 females). Coagulation parameters were similar in CD and UC patients and only plasminogen was increased in CD patients [97.4 (17.0) versus 91.6 (13.3), p = 0.035], when comparing with UC patients. The determined values were in the range of the reference values described in literature for the standard population. During the follow-up period, none of the patients experienced a TE that demanded hospitalization. CONCLUSION In our study, acquired and inherited risk factors for TE and changes in coagulation parameters did not show to influence prothrombotic predisposition in IBD patients. As such, the clinical relevance of measuring coagulation parameters in this population is questionable. TRIAL REGISTRY NCT05162339 (ClinicalTrials.gov ID).
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Affiliation(s)
- Ana Catarina Carvalho
- Department of Gastroenterology, Centro
Hospitalar Tondela-Viseu, E.P.E., Viseu, Portugal
| | - Juliana Pinho
- Department of Gastroenterology, Centro
Hospitalar Tondela-Viseu, E.P.E., Viseu, Portugal
| | - Eugénia Cancela
- Department of Gastroenterology, Centro
Hospitalar Tondela-Viseu, E.P.E., Viseu, Portugal
| | - Hugo Marcelo Vieira
- Department of Public Health, Unidade de Saúde
Pública ACeS Maia/Valongo, Porto, Portugal
| | - Américo Silva
- Department of Gastroenterology, Centro
Hospitalar Tondela-Viseu, E.P.E., Viseu, Portugal
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32
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Zhang XY, Dong HC, Wang WF, Zhang Y. Risk of venous thromboembolism in children and adolescents with inflammatory bowel disease: A systematic review and meta-analysis. World J Gastroenterol 2022; 28:1705-1717. [PMID: 35581968 PMCID: PMC9048785 DOI: 10.3748/wjg.v28.i16.1705] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 11/01/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A two- to three-fold increased risk of venous thrombotic events (VTE) has been demonstrated in patients with inflammatory bowel disease (IBD) compared to the general population, but less is known about the risk of VTE in child- and pediatric-onset IBD. In recent years, several studies have reported the rising incidence rate of VTE in juvenile patients with IBD, and the related risk factors have been explored. AIM To evaluate the risk of VTE in children and adolescents with IBD. METHODS Articles published up to April 2021 were retrieved from PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, and WANFANG. Data from observational studies and clinical work were extracted. The outcome was the occurrence of VTE according to the type of IBD. The available odds ratio (OR) and the corresponding 95% confidence interval (CI) were extracted to compare the outcomes. Effect size (P), odds ratio (OR), and 95%CI were used to assess the association between VTE risk and IBD disease. Subgroup analyses stratified by subtypes of VTE and IBD were performed. RESULTS Twelve studies (7450272 IBD patients) were included in the meta-analysis. Child and adolescent IBD patients showed increased VTE risk (P = 0.02, 95%CI: 0.01-0.03). Subgroup analyses stratified by IBD (ulcerative colitis (UC): P = 0.05, 95%CI: 0.03-0.06; Crohn's disease (CD): P = 0.02, 95%CI: 0.00-0.04) and VTE subtypes (portal vein thrombosis: P = 0.04, 95%CI: 0.02-0.06; deep vein thrombosis: P = 0.03, 95%CI: 0.01-0.05; central venous catheter-related thrombosis: P = 0.23, 95%CI: 0.00-0.46; thromboembolic events: P = 0.02, 95%CI: 0.01-0.03) revealed a significant correlation between VTE risk and IBD. Patients with IBD were more susceptible to VTE risk than those without IBD (OR = 2.99, 95%CI: 1.45-6.18). The funnel plot was asymmetric, suggesting the presence of significant publication bias. Pediatric and adolescent IBD patients have an increased VTE risk. UC and CD patients exhibited a high risk of VTE. The risk of VTE subtypes was increased in IBD patients. CONCLUSION The current meta-analysis showed that the incidence and risk of VTE are significantly increased in pediatric and adolescent IBD patients. Thus, IBD might be a risk factor for VTE in children and young adults. High-quality prospective cohort studies are necessary to confirm these findings.
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Affiliation(s)
- Xin-Yue Zhang
- Department of Traditional Chinese Medicine, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310005, Zhejiang Province, China
| | - Hai-Cheng Dong
- Department of Traditional Chinese Medicine, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310005, Zhejiang Province, China
| | - Wen-Fei Wang
- Department of Traditional Chinese Medicine, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310005, Zhejiang Province, China
| | - Yao Zhang
- Department of Traditional Chinese Medicine, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310005, Zhejiang Province, China
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Bromfield B, Schwartz M. Bilateral pulmonary embolism and pulmonary infarctions in active ulcerative colitis. BMJ Case Rep 2022; 15:e249428. [PMID: 35264397 PMCID: PMC8915276 DOI: 10.1136/bcr-2022-249428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2022] [Indexed: 01/06/2023] Open
Abstract
Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) and they primarily involve the intestines and confer an increased risk of thromboembolism (TE). Here we report a case of a young man with active ulcerative colitis (UC) who presented with shortness of breath and syncope. He was found on imaging to have an extensive bilateral pulmonary embolism (PE) and right heart strain with associated pulmonary infarctions. The patient was initially managed with a heparin infusion and subsequently transitioned to a direct acting oral anticoagulant (DOAC) with clinical improvement in his symptoms.
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Affiliation(s)
| | - Marc Schwartz
- Gastroenterology and Hepatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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34
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Ambrose PA, Goodman WA. Impact of COVID-19 on Patients with Inflammatory Bowel Disease. JOURNAL OF EXPLORATORY RESEARCH IN PHARMACOLOGY 2022; 7:37-44. [PMID: 35966234 PMCID: PMC9373928 DOI: 10.14218/jerp.2021.00014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan, China, in late 2019. Responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2 is one of three structurally similar beta-coronaviruses that can cause a strong upregulation of cytokines referred to as cytokine release syndrome (CRS). Unresolved CRS leads to respiratory symptoms, including pneumonia, and in more severe cases, acute respiratory distress syndrome (ARDS). Although COVID-19 is widely known for these hallmark respiratory symptoms, it also impacts the gut, causing gastrointestinal (GI) tract inflammation and diarrhea. COVID-19's GI symptoms may be due to the high intestinal expression of angiotensin converting enzyme-2 receptors, which are for the binding of SARS-CoV-2 viral particles. Reports have shown that SARS-CoV-2 can be passed through fecal matter, with one study finding that 48.1% of COVID-19 patients expressed viral SARS-CoV-2 mRNA in their stool. Given that the GI tract is a target tissue affected by COVID-19, this causes concern for those with underlying GI pathologies, such as inflammatory bowel disease (IBD). Regrettably, there have been only limited studies on the impact of COVID-19 on gut health, and the impact of COVID-19 on intestinal inflammation among IBD patients remains unclear. In particular, questions regarding susceptibility to SARS-CoV-2 infection, clinical impact of COVID-19 on IBD, and the potential influence of age, sex, and immunosuppressant medications are still poorly understood. An improved understanding of these issues is needed to address the unique risks of COVID-19 among IBD patients, as well as the potential impact of SARS-CoV-2 on the host intestinal microbiota.
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Affiliation(s)
- Paula A. Ambrose
- Department of Pathology, Case Western Reserve University School of Medicine, OH, USA
| | - Wendy A. Goodman
- Department of Pathology, Case Western Reserve University School of Medicine, OH, USA
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35
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Le Mao R, Orione C, de Moreuil C, Tromeur C, Hoffmann C, Fauché A, Robin P, Didier R, Guegan M, Jiménez D, Le Moigne E, Leroyer C, Lacut K, Couturaud F. Risk stratification for predicting recurrent venous thromboembolism after discontinuation of anticoagulation: a post-hoc analysis of a French prospective multicenter study. Eur Respir J 2022; 60:13993003.03002-2021. [PMID: 35210315 DOI: 10.1183/13993003.03002-2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 01/30/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND We aimed to validate and to refine current recurrent venous thromboembolism (VTE) risk classification. METHODS We performed a post-hoc analysis of a multicentre cohort, including 1,881 patients with a first symptomatic VTE prospectively followed after anticoagulation discontinuation. The primary objective was to validate the International Society of Thrombosis and Haemostasis (ISTH) risk classification in predicting recurrence risk. Secondary objective was to evaluate a refined ISTH classification based on recurrence risk estimate for each individual risk factors. RESULTS During a 4.8-year median follow-up after anticoagulation discontinuation, symptomatic recurrent VTE occurred in 230 patients (12.2%). Based on ISTH classification, patients with unprovoked VTE or VTE with minor or major persistent risk factor had a 2-fold increased recurrence risk as compared to those with VTE and major transient risk factor. Recurrence risk was not increased in patients with minor transient factor (Hazard Ratio[HR] 1.31;95%CI0.84-2.06). Individual risk factors analysis identified hormone-related VTE (pregnancy: HR 0.26; 95%CI0.08-0.82; estrogens: HR 0.25; 95%CI0.14-0.47) and amyotrophic lateral sclerosis (HR 5.84; 95%CI1.82-18.70). After reclassification of these factors as major transient for the former and major persistent for the latter, refined ISTH classification allowed to accurately discriminate between patients at low-risk (i.e., with major transient risk factor) and those at high-risk of recurrence (i.e., without major transient risk factors). CONCLUSIONS Among patients who stopped anticoagulation after a first VTE, a refined ISTH classification based on recurrence risk intensity of individual factors allowed to discriminate between patients at low-recurrence risk, including hormonal exposure in women, and patients at high-recurrence risk.
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Affiliation(s)
- Raphael Le Mao
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France .,Centre d'Investigation Clinique INSERM 1412, Brest, France
| | - Charles Orione
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France
| | - Claire de Moreuil
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France
| | - Cécile Tromeur
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France.,FCRIN INNOVTE network, Brest, France
| | - Clément Hoffmann
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France
| | - Alexandre Fauché
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France
| | - Philippe Robin
- Centre d'Investigation Clinique INSERM 1412, Brest, France.,FCRIN INNOVTE network, Brest, France.,Service de médecine nucléaire, EA3878, CHU de Brest, Univ_Brest, Brest, France
| | - Romain Didier
- Centre d'Investigation Clinique INSERM 1412, Brest, France.,Service de cardiologie, EA3878, CHU de Brest, Univ_Brest, Brest, France
| | - Marie Guegan
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France.,FCRIN INNOVTE network, Brest, France
| | - David Jiménez
- Respiratory Department, Hospital Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Medicine Department, Universidad de Alcalá, (IRYCIS), Madrid, Spain.,CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Emmanuelle Le Moigne
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France.,FCRIN INNOVTE network, Brest, France
| | - Christophe Leroyer
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France.,FCRIN INNOVTE network, Brest, France
| | - Karine Lacut
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France.,FCRIN INNOVTE network, Brest, France.,In memory of Karine Lacut
| | - Francis Couturaud
- Département de médecine interne et pneumologie, EA3878, CHU de Brest, Univ_Brest, Brest, France.,Centre d'Investigation Clinique INSERM 1412, Brest, France.,FCRIN INNOVTE network, Brest, France
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36
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Spinelli A, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, Bachmann O, Bettenworth D, Chaparro M, Czuber-Dochan W, Eder P, Ellul P, Fidalgo C, Fiorino G, Gionchetti P, Gisbert JP, Gordon H, Hedin C, Holubar S, Iacucci M, Karmiris K, Katsanos K, Kopylov U, Lakatos PL, Lytras T, Lyutakov I, Noor N, Pellino G, Piovani D, Savarino E, Selvaggi F, Verstockt B, Doherty G, Raine T, Panis Y. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment. J Crohns Colitis 2022; 16:179-189. [PMID: 34635910 DOI: 10.1093/ecco-jcc/jjab177] [Citation(s) in RCA: 132] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.
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Affiliation(s)
- Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, and Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Stefanos Bonovas
- Department of Biomedical Sciences, and IRCCS Humanitas Research Hospital, Milan, Italy
| | - Johan Burisch
- Gastrounit, Medical Division, and Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Torsten Kucharzik
- Department of Gastroenterology, Lüneburg Hospital, University of Hamburg, Lüneburg, Germany
| | - Michel Adamina
- Department of Surgery, Clinic of Visceral and Thoracic Surgery, Cantonal Hospital Winterthur, Zurich
- Department of Biomedical Engineering, Clinical Research and Artificial Intelligence in Surgery, Faculty of Medicine, University of Basel, Allschwil, Switzerland
| | - Vito Annese
- Department of Gastroenterology, Fakeeh University Hospital, Dubai, UAE
| | - Oliver Bachmann
- Department of Internal Medicine I, Siloah St. Trudpert Hospital, Pforzheim
- Hannover Medical School, Hannover, Germany
| | - Dominik Bettenworth
- University Hospital Munster, Department of Medicine B - Gastroenterology and Hepatology, Munster, Germany
| | - Maria Chaparro
- Gastroenterology Unit, IIS-IP, Universidad Autónoma de Madrid [UAM], CIBEREHD, Madrid, Spain
| | - Wladyslawa Czuber-Dochan
- King's College London, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, London, UK
| | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznań University of Medical Sciences, and Heliodor Święcicki University Hospital, Poznań, Poland
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - Catarina Fidalgo
- Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal
| | - Gionata Fiorino
- Department of Biomedical Sciences, Humanitas University, and IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Paolo Gionchetti
- IBD Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna DIMEC, University of Bologna, Bologna, Italy
| | - Javier P Gisbert
- Gastroenterology Unit, IIS-IP, Universidad Autónoma de Madrid [UAM], CIBEREHD, Madrid, Spain
| | - Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - Charlotte Hedin
- Karolinska Institutet, Department of Medicine Solna, and Karolinska University Hospital, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, University of Birmingham, and Division of Gastroenterology, University Hospitals Birmingham NHS Trust, Birmingham, UK
| | | | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Tel-HaShomer Sheba Medical Center, Ramat Gan, and Sackler Medical School, Tel Aviv, Israel
| | - Peter L Lakatos
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC, Canada
- 1st Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Theodore Lytras
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Ivan Lyutakov
- Department of Gastroenterology, University Hospital 'Tsaritsa Yoanna - ISUL', Medical University Sofia, Sofia, Bulgaria
| | - Nurulamin Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Universitá degli Studi della Campania "Luigi Vanvitelli", Naples, Italy, and Colorectal Surgery, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, and IRCCS Humanitas Research Hospital, Milan, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Francesco Selvaggi
- Department of Advanced Medical and Surgical Sciences, Universitá degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, and Department of Chronic Diseases, Metabolism and Ageing, TARGID - IBD, KU Leuven, Leuven, Belgium
| | - Glen Doherty
- Department of Gastroenterology and Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Yves Panis
- Department of Colorectal Surgery, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy and Université of Paris, France
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Moukalled NM, Hashash JG, Taher AT. Inflammatory Bowel Disease: An Indication to Screen for Thrombophilia? Diseases 2022; 10:diseases10010014. [PMID: 35323181 PMCID: PMC8947449 DOI: 10.3390/diseases10010014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/17/2022] [Accepted: 02/18/2022] [Indexed: 11/30/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are systemic conditions characterized by multiple intestinal and extra-intestinal manifestations related to the associated chronic inflammatory state. Among their diverse extra-intestinal complications, venous thromboembolism (VTE) remains one of the most under recognized causes of morbidity and mortality in these patients, highlighting the need for a better understanding of the underlying mechanism of hypercoagulability, in addition to the role of acquired and inherited risk factors that further increase the risk of thrombosis with its impact on patients’ outcomes. We hereby present a review of the data regarding thrombosis in the setting of IBD, elucidating the possible role for screening in this high-risk category of patients and specifically in areas where inherited thrombophilia is expected to be highly prevalent, reporting two patients with IBD, one who developed a cerebrovascular event and another one who had recurrent VTE events; nevertheless, both of them had inherited thrombophilic mutations. The identification of specific genetic abnormalities in those patients reintroduces the controversy related to the need to screen a specific category of patients with IBD for hereditary thrombophilia, especially in regions characterized by a higher prevalence of such thrombophilic alterations.
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Affiliation(s)
- Nour M. Moukalled
- Division of Hematology and Oncology, Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, P.O. Box 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon;
- Correspondence:
| | - Jana G. Hashash
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Ali T. Taher
- Division of Hematology and Oncology, Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, P.O. Box 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon;
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38
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De Laffolie J, Ballauff A, Wirth S, Blueml C, Rommel FR, Claßen M, Laaß M, Lang T, Hauer AC. Occurrence of Thromboembolism in Paediatric Patients With Inflammatory Bowel Disease: Data From the CEDATA-GPGE Registry. Front Pediatr 2022; 10:883183. [PMID: 35722497 PMCID: PMC9204097 DOI: 10.3389/fped.2022.883183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/14/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Among patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4-0.9% in hospitalised children with IBD. METHODS Cases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung - large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist. RESULTS Over 10 years, 4,153 paediatric patients with IBD (0-18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn's disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56-22.33, p = 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela. CONCLUSION Paediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.
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Affiliation(s)
- Jan De Laffolie
- Department of General Pediatrics and Neonatology, University of Giessen, Giessen, Germany
| | | | - Stefan Wirth
- Kinderklinik, Helios Klinikum Wuppertal, Wuppertal, Germany
| | - Carolin Blueml
- Department of Paediatrics, Philipps-University Marburg, Marburg, Germany
| | - Frank Risto Rommel
- Department of General Pediatrics and Neonatology, University of Giessen, Giessen, Germany
| | | | - Martin Laaß
- Children's Hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Thomas Lang
- Kinderklinik Regensburg, Regensburg, Germany
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39
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Florin J, Stalder O, Baumgartner C, Méan M, Rodondi N, Aujesky D. Do Patients with a Family or Personal History of Venous Thromboembolism have an Increased Risk of Recurrence? Thromb Haemost 2021; 122:1017-1026. [PMID: 34963186 DOI: 10.1055/s-0041-1740184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND A family (FH) and personal history (PH) of venous thromboembolism (VTE) are commonly evaluated risk factors for recurrence. We examined the association between FH/PH of VTE and the risk of recurrence and whether a stronger history status (i.e., both FH/PH vs. no FH/PH) carries an increased recurrence risk. METHODS We prospectively followed 813 patients aged ≥ 65 years with acute VTE from 9 Swiss hospitals. We classified patients into four groups: no FH/PH, FH only, PH only, and both FH/PH. The primary outcome was recurrent VTE during the full observation period. We examined the association between FH/PH status and the time to VTE recurrence using competing risk regression, adjusting for confounders and periods of anticoagulation. RESULTS Of 813 patients with VTE, 59% had no FH/PH, 11% a FH only, 24% a PH only, and 7% had both a FH and PH of VTE. Overall, 105 patients had recurrent VTE during the full observation period. After adjustment, patients with a FH only (subhazard ratio [SHR] 0.8, 95% confidence interval [CI] 0.4-1.7), PH only (SHR 1.5, 95% CI 0.9-2.5), and both FH/PH (SHR 1.4, 95% CI 0.6-3.1) did not have an increased risk of recurrent VTE compared with those without FH/PH. When we considered the period after the completion of initial anticoagulation only, the results were similar. CONCLUSION Our findings indicate that in patients with acute VTE, a FH and/or PH of VTE does not convey an increased risk of recurrent VTE. In particular, we did not find a "dose-effect" relationship between FH/PH status and VTE recurrence.
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Affiliation(s)
- Jonas Florin
- Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland
| | | | - Christine Baumgartner
- Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland
| | - Marie Méan
- Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
| | - Nicolas Rodondi
- Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.,Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
| | - Drahomir Aujesky
- Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland
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40
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Olivera PA, Zuily S, Kotze PG, Regnault V, Al Awadhi S, Bossuyt P, Gearry RB, Ghosh S, Kobayashi T, Lacolley P, Louis E, Magro F, Ng SC, Papa A, Raine T, Teixeira FV, Rubin DT, Danese S, Peyrin-Biroulet L. International consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021; 18:857-873. [PMID: 34453143 PMCID: PMC8395387 DOI: 10.1038/s41575-021-00492-8] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/05/2021] [Indexed: 12/11/2022]
Abstract
Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as 'fully agree' or 'mostly agree' with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events.
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Affiliation(s)
- Pablo A Olivera
- Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
| | - Stephane Zuily
- Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-lès-Nancy, France
- University of Lorraine, INSERM, DCAC, Nancy, France
| | - Paulo G Kotze
- IBD outpatient clinics, Colorectal Surgery Unit, Catholic University of Paraná (PUCPR), Curitiba, Brazil
| | | | - Sameer Al Awadhi
- Gastroenterology Division, Rashid Hospital, Dubai Health Authority, Dubai, UAE
| | - Peter Bossuyt
- Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Subrata Ghosh
- NIHR Biomedical Research Centre, University of Birmingham and University Hospitals NHS Foundation Trust, Birmingham, UK
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan
| | | | - Edouard Louis
- Department of Gastroenterology, CHU Liège University Hospital, Liège, Belgium
| | - Fernando Magro
- Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Alfredo Papa
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Catholic University of Rome, Rome, Italy
| | - Tim Raine
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - David T Rubin
- University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and INSERM NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France.
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Chen H, Wu X, Xu C, Lin J, Liu Z. Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases. PRECISION CLINICAL MEDICINE 2021; 4:246-257. [PMID: 35692862 PMCID: PMC8982532 DOI: 10.1093/pcmedi/pbab025] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/10/2021] [Accepted: 11/11/2021] [Indexed: 02/06/2023] Open
Abstract
Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.
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Affiliation(s)
- Huimin Chen
- Center for Inflammatory Bowel Disease Research, the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Xiaohan Wu
- Center for Inflammatory Bowel Disease Research, the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Chunjin Xu
- Department of Gastroenterology, the First People's Hospital of Shangqiu City Affiliated to Xinxiang Medical University, Shangqiu 476100, China
| | - Jian Lin
- Department of Gastroenterology, Affiliated Hospital of Putian University, Putian 351106, China
| | - Zhanju Liu
- Center for Inflammatory Bowel Disease Research, the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
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42
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Stadnicki A, Stadnicka I. Venous and arterial thromboembolism in patients with inflammatory bowel diseases. World J Gastroenterol 2021; 27:6757-6774. [PMID: 34790006 PMCID: PMC8567469 DOI: 10.3748/wjg.v27.i40.6757] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/22/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
The risk of thromboembolism (TE) is increased in patients with inflammatory bowel disease (IBD), mainly due to an increased risk of venous TE (VTE). The risk of arterial TE (ATE) is less pronounced, but an increased risk of cardiovascular diseases needs to be addressed in IBD patients. IBD predisposes to arterial and venous thrombosis through similar prothrombotic mechanisms, including triggering activation of coagulation, in part mediated by impairment of the intestinal barrier and released bacterial components. VTE in IBD has clinical specificities, i.e., an earlier first episode in life, high rates during both active and remission stages, higher recurrence rates, and poor prognosis. The increased likelihood of VTE in IBD patients may be related to surgery, the use of medications such as corticosteroids or tofacitinib, whereas infliximab is antithrombotic. Long-term complications of VTE can include post-thrombotic syndrome and high recurrence rate during post-hospital discharge. A global clot lysis assay may be useful in identifying patients with IBD who are at risk for TE. Many VTEs occur in IBD outpatients; therefore, outpatient prophylaxis in high-risk patients is recommended. It is crucial to continue focusing on prevention and adequate treatment of VTE in patients with IBD.
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Affiliation(s)
- Antoni Stadnicki
- Department of Physiology, Faculty of Medicine, University of Technology, Katowice 41-209, Poland
| | - Izabela Stadnicka
- Department of Molecular Medicine, Medical University of Silesia, Faculty of Pharmacy, Sosnowiec 41-200, Poland
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43
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Scharrer S, Primas C, Eichinger S, Tonko S, Kutschera M, Koch R, Blesl A, Reinisch W, Mayer A, Haas T, Feichtenschlager T, Fuchssteiner H, Steiner P, Ludwiczek O, Platzer R, Miehsler W, Tillinger W, Apostol S, Schmid A, Schweiger K, Vogelsang H, Dejaco C, Herkner H, Novacek G. Inflammatory Bowel Disease and Risk of Major Bleeding During Anticoagulation for Venous Thromboembolism. Inflamm Bowel Dis 2021; 27:1773-1783. [PMID: 33386735 DOI: 10.1093/ibd/izaa337] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. METHODS This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. RESULTS We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. CONCLUSION The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.
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Affiliation(s)
- Susanna Scharrer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Christian Primas
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Sabine Eichinger
- Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
| | - Sebastian Tonko
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.,Praxis am rhy AG, Kriessern, Switzerland
| | - Maximilian Kutschera
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Robert Koch
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Andreas Blesl
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Walter Reinisch
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Andreas Mayer
- Department of Internal Medicine II, Universitätsklinikum St. Pölten, St. Pölten, Austria
| | | | | | - Harry Fuchssteiner
- Department of Internal Medicine IV, Hospital Elisabethinen Linz, Linz, Austria
| | - Pius Steiner
- Department of Internal Medicine I, Hospital Wels-Grieskirchen, Wels, Austria
| | | | - Reingard Platzer
- Department of Internal Medicine I, Hospital Wiener Neustadt, Wiener Neustadt, Austria
| | - Wolfgang Miehsler
- Department of Internal Medicine, Hospital Brothers of St. John of God Salzburg, Salzburg, Austria
| | | | - Sigrid Apostol
- Department of Internal Medicine, Hietzing Clinic, Vienna, Austria
| | - Alfons Schmid
- Department of Internal Medicine 2, Danube Hospital, Vienna, Austria
| | - Karin Schweiger
- Department of Internal Medicine 4, Ottakring Clinic, Vienna, Austria
| | - Harald Vogelsang
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Clemens Dejaco
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Harald Herkner
- Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
| | - Gottfried Novacek
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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Story L, Rafique S, Samadi N, Mawdsley J, Singh B, Banerjee A. Lower gastrointestinal bleeding in pregnancy: Differential diagnosis, assessment and management. Obstet Med 2021; 14:129-134. [PMID: 34646340 PMCID: PMC8504301 DOI: 10.1177/1753495x20948300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/15/2020] [Accepted: 07/15/2020] [Indexed: 12/16/2022] Open
Abstract
Rectal bleeding is a common symptom experienced by pregnant women. Although the majority of cases are attributable to benign conditions such as haemorrhoids and anal fissures, other more serious diagnoses such as inflammatory bowel disease and malignancy should not be overlooked. Most investigations are safe during pregnancy and these should not be withheld as significant implications on both fetal and maternal morbidity may result. In these cases, a multidisciplinary team approach is essential. This review explores the differential diagnosis, investigation and management of rectal bleeding during pregnancy.
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Affiliation(s)
- L Story
- Department of Women and Children's Health King's College, London, UK.,Women's Services, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - S Rafique
- King's College London Medical School, London, UK
| | - N Samadi
- King's College London Medical School, London, UK
| | - J Mawdsley
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - B Singh
- Department of Surgery, University Hospitals Leicester, Leicester, UK
| | - A Banerjee
- Women's Services, Guy's and St Thomas' NHS Foundation Trust, London, UK
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45
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Ghoneim S, Weissman S, Wang L, Aziz M, Atoot A, Sandhu D, Swaminath A, Feuerstein JD. Impact of inflammatory bowel disease on hospital outcomes in acute ischemic stroke: a nationwide cohort study. Int J Colorectal Dis 2021; 36:1759-1764. [PMID: 33733312 DOI: 10.1007/s00384-021-03912-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Patients with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events. The impact IBD has on arterial thrombosis is not well characterized. We aimed to identify the impact of IBD on hospital outcomes in patients admitted for acute ischemic stroke (AIS). METHODS This is a retrospective cohort study utilizing the 2017 National Inpatient Sample. We identified all adult patients with a principal diagnosis of AIS and compared those with a concurrent diagnosis of IBD to those without-subgrouped by ulcerative colitis (UC) and Crohn's disease (CD). Outcomes were mortality and healthcare usage among IBD patients with AIS. Multivariate analysis was used to control for confounders. Analyses were performed using STATA. RESULTS Five hundred twenty-four thousand and forty-five patients were admitted for AIS in 2017; of them 2200 (0.41%) had a concurrent diagnosis of IBD. The presence of IBD did not significantly affect in-hospital mortality (4.09% vs. 4.01%) among patients admitted for AIS [OR 1.07 95% CI: 0.65-1.76], with similar findings upon subgroup analysis of UC [OR 0.91, 95% CI: 0.39-2.09] and CD [OR 1.17, 95% CI: 0.62-2.19]. Mean hospital length of stay and charges/costs in AIS were similar irrespective of IBD. CONCLUSIONS UC and CD do not appear to be associated with a higher risk of mortality or increased healthcare usage in AIS. AIS risk assessment in patients with IBD is important but should be done in a similar fashion to the general population.
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Affiliation(s)
- Sara Ghoneim
- Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH, USA
| | - Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, 7600 River Road, North Bergen, NJ, 07047, USA.
| | - Linda Wang
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Muhammad Aziz
- Division of Gastroenterology, University of Toledo Medical Center, Toledo, OH, USA
| | - Adam Atoot
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, 7600 River Road, North Bergen, NJ, 07047, USA
| | - Dalbir Sandhu
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Arun Swaminath
- Division of Gastroenterology, Inflammatory Bowel Disease Program, Lenox Hill Hospital, New York, NY, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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46
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Sleutjes JAM, van Lennep JER, van der Woude CJ, de Vries AC. Thromboembolic and atherosclerotic cardiovascular events in inflammatory bowel disease: epidemiology, pathogenesis and clinical management. Therap Adv Gastroenterol 2021; 14:17562848211032126. [PMID: 34377149 PMCID: PMC8323448 DOI: 10.1177/17562848211032126] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 05/27/2021] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). The increased risk of CVD concerns an increased risk of venous thromboembolism (VTE), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), at corresponding relative risks of 2.5, 1.2 and 2.0, respectively, as compared with the general population. Especially young patients under the age of 40 years run a relatively high risk of these complications when compared with the general population. Chronic systemic inflammation causes a hypercoagulable state leading to the prothrombotic tendency characteristic of VTE, and accelerates all stages involved during atherogenesis in ASCVD. Increased awareness of VTE risk is warranted in patients with extensive colonic disease in both ulcerative colitis and Crohn's disease, as well as during hospitalization, especially when patients are scheduled for surgery. Similarly, critical periods for ASCVD events are the 3 months prior to and 3 months after an IBD-related hospital admission. The increased ASCVD risk is not fully explained by an increased prevalence of traditional risk factors and includes pro-atherogenc lipid profiles with high levels of small dense low-density lipoprotein cholesterol particles and dysfunctional high-density lipoprotein cholesterol. Risk factors associated with HF are location and extent of inflammation, female sex, and age exceeding 40 years. A dose-dependent increase of overall CVD risk has been reported for corticosteroids. Immunomodulating maintenance therapy might reduce CVD risk in IBD, not only by a direct reduction of chronic systemic inflammation but possibly also by a direct effect of IBD medication on platelet aggregation, endothelial function and lipid and glucose metabolism. More data are needed to define these effects accurately. Despite accumulating evidence on the increased CVD risk in IBD, congruent recommendations to develop preventive strategies are lacking. This literature review provides an overview of current knowledge and identifies gaps in evidence regarding CVD risk in IBD, by discussing epidemiology, pathogenesis, and clinical management.
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Affiliation(s)
- Jasmijn A. M. Sleutjes
- Department of Gastroenterology and Hepatology,
Erasmus Medical Center, Rotterdam, the Netherlands
| | | | - C. Janneke van der Woude
- Department of Gastroenterology and Hepatology,
Erasmus Medical Center, Rotterdam, the Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology and Hepatology,
Erasmus Medical Center, Dr. Molewaterplein 40, Room Na-618, Rotterdam
3015GD, The Netherlands
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Dos Santos Ramos A, Viana GCS, de Macedo Brigido M, Almeida JF. Neutrophil extracellular traps in inflammatory bowel diseases: Implications in pathogenesis and therapeutic targets. Pharmacol Res 2021; 171:105779. [PMID: 34298111 DOI: 10.1016/j.phrs.2021.105779] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 07/04/2021] [Accepted: 07/19/2021] [Indexed: 02/07/2023]
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD). Among the various immune cells involved in IBD, neutrophils are the first to infiltrate and appear to contribute to the impairment of the epithelial barrier, destruction of tissues by oxidative and proteolytic damage, as well as to the perpetuation of inflammation by the release of cytokines and chemokines associated with pro-inflammatory effects. In addition to basic effector mechanisms, such as phagocytosis and chemotaxis, neutrophils can also form extracellular traps (NETs), which is made up of a mesh-like structure - which contains its chromatin (DNA + histones) together with granules and enzymes, such as myeloperoxidase (MPO) and neutrophilic elastase (NE) - and that acts as a trap that can result in the death of extracellular pathogens and/or can promote tissue damage. Recent evidence indicates that NETs also play an important and significant role in the pathogenesis of IBD. Previous studies have reported increased levels of NETs in tissue and serum samples from patients with IBD, as well as in experimental colitis. In this review, we discuss current knowledge about the formation of NETs and their role in the pathophysiology of IBD, pointing out potential mechanisms by which NETs promote tissue damage, as well as their involvement in complications associated with IBD. In addition, we propose potential targets for therapy to regulate the production of NETs, making it possible to expand the current spectrum of therapies for IBD.
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Affiliation(s)
- Anderson Dos Santos Ramos
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
| | | | | | - Juliana Franco Almeida
- Department of Cellular Biology, University of Brasilia, Brasilia, Brazil; Department of Cellular and Molecular Biology, Federal University of Paraíba, Paraíba, Brazil.
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Preoperative prevalence and risk factors of deep-vein thrombosis in Japanese surgical patients with ulcerative colitis: a retrospective investigational study. Surg Today 2021; 52:251-259. [PMID: 34236523 DOI: 10.1007/s00595-021-02335-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/04/2021] [Indexed: 12/27/2022]
Abstract
PURPOSE The purpose of this study was to clarify the perioperative deep-vein thrombosis (DVT) prevalence and its risk factors in surgical ulcerative colitis (UC) patients by comparing the results with those in surgical colorectal cancer (CRC) patients at a high risk of perioperative venous thrombosis. METHODS This retrospective, observational study included patients who underwent surgery for UC or CRC between January 2013 and October 2019. Consecutive surgical patients with a positive D-dimer assay result (≥ 1.0 µg/ml) underwent lower-extremity venous ultrasonography. The prevalence and risk factors for preoperative DVT were examined in UC patients. RESULTS A total of 101 UC patients and 593 CRC patients were deemed eligible. Among the D-dimer positive cases, there were no significant differences between the two groups in the preoperative DVT prevalence (UC: 21.8% vs. CRC: 28.8%, p = 0.151), distal type (18.8% vs. 27.2%, p = 0.086), or proximal type (5.9% vs. 4.2%, p = 0.434). Furthermore, multivariate analyses showed that an older age, overweight status, poor ASA status, and a high preoperative dose of steroid were independent risk factors for preoperative DVT in UC surgical patients. CONCLUSIONS The risk of perioperative thrombosis in UC patients was considered similar to that in CRC, so active thromboprophylaxis should be administered to UC patients while paying attention to bleeding. TRIAL REGISTRATION This study was registered with the Japanese Clinical Trials Registry as UMIN000042004 ( http://www.umin.ac.jp/ctr/index.htm ).
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49
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Defining the Economic Burden of Perioperative Venous Thromboembolism in Inflammatory Bowel Disease in the United States. Dis Colon Rectum 2021; 64:871-880. [PMID: 33833140 DOI: 10.1097/dcr.0000000000001942] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/06/2022]
Abstract
BACKGROUND Patients with IBD are at increased risk of venous thromboembolism. OBJECTIVE This study aims to define the economic burden associated with inpatient venous thromboembolism after surgery for IBD that presently remains undefined. DESIGN This study is a retrospective, cross-sectional analysis using the National Inpatient Sample from 2004 to 2014. SETTING Participating hospitals across the United States were sampled. PATIENTS The International Classification of Diseases, 9th Revision codes were used to identify patients with a primary diagnosis of IBD. INTERVENTIONS Major abdominopelvic bowel surgery was performed. MAIN OUTCOME MEASURES The primary outcome measured was the occurrence of inpatient venous thromboembolism. Univariate and multivariable patient- and hospital-level logistic regression models were used to compare patient characteristics, hospital characteristics, and outcomes between venous thromboembolism and non-venous thromboembolism cohorts. Total average direct costs were then compared between cohorts, and the resulting difference was extrapolated to the national population. RESULTS Of 26,080 patients included, inpatient venous thromboembolism was identified in 581 (2.2%). On multivariable analysis, diagnosis of ulcerative colitis, transfer status, length of preoperative hospitalization, and insurance status were independently associated with inpatient venous thromboembolism. Patients with venous thromboembolism were observed to be associated with an increased median length of stay (17.6 vs 6.7 days; p < 0.001) and higher inpatient mortality (5.0% vs 1.1%; OR 4.7, SE 3.2-7.0; p < 0.001). After adjusting for clinically relevant covariates, the additional cost associated with each inpatient venous thromboembolism was $31,551 (95% CI, $29,136-$33,965). LIMITATIONS Our study is limited by the administrative nature of the National Inpatient Sample database, which limits our ability to evaluate the impact of clinical covariates (eg, use of venous thromboembolism chemoprophylaxis, steroid use, and nutrition status). CONCLUSION Inpatient venous thromboembolism in abdominopelvic surgery for IBD is an infrequent, yet costly, morbid complication. Given the magnitude of patient morbidity and economic burden, venous thromboembolism prevention should be a national quality improvement and research priority. See Video Abstract at http://links.lww.com/DCR/B544. DEFINICIN IMPACTO ECONMICO DE LA TROMBOEMBOLIA VENOSA PERIOPERATORIA EN LA ENFERMEDAD INFLAMATORIA INTESTINAL EN LOS ESTADOS UNIDOS ANTECEDENTES:Pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de tromboembolismo venoso (TEV).OBJETIVO:Definir el impacto económico de TEV hospitalaria después de la cirugía por EII, que en la actualidad permanece indefinida.DISEÑO:Un análisis transversal retrospectivo utilizando la Muestra Nacional de Pacientes Internos (NIS) de 2004 a 2014.ENTORNO CLINICO:Hospitales participantes muestreados en los Estados Unidos.PACIENTES:Se utilizaron los códigos de la 9ª edición de la Clasificación Internacional de Enfermedades (ICD-9) para identificar a los pacientes con diagnóstico primario de EII.INTERVENCIONES:Cirugía mayor abdominopélvica intestinal.PRINCIPALES MEDIDAS DE VALORACION:Incidencia de TEV en pacientes hospitalizados, utilizando modelos de regresión logística univariado y multivariable a nivel de pacientes y hospitales para comparar las características de los pacientes, las características del hospital y los resultados entre las cohortes de TEV y no TEV. Se compararon los costos directos promedio totales entre cohortes y la diferencia resultante extrapolando a la población nacional.RESULTADOS:De 26080 pacientes incluidos, se identificó TEV hospitalario en 581 (2,2%). En análisis multivariable, el diagnóstico de colitis ulcerosa, el estado de transferencia (entre centros hospitalarios), la duración de la hospitalización preoperatoria y el nivel de seguro medico se asociaron de forma independiente con la TEV hospitalaria. Se observó que los pacientes con TEV se asociaron con un aumento de la duración media de la estancia (17,6 versus a 6,7 días; p <0,001) y una mayor mortalidad hospitalaria (5,0% versus a 1,1%; OR 4,7, SE 3,2 -7,0; p <0,001). Después de ajustar las covariables clínicamente relevantes, el costo adicional asociado con cada TEV para pacientes hospitalizados fue de $ 31,551 USD (95% C.I. $ 29,136 - $ 33,965).LIMITACIONES:Estudio limitado por la naturaleza administrativa de la base de datos del NIS, que limita nuestra capacidad para evaluar el impacto de las covariables clínicas (por ejemplo, el uso de quimioprofilaxis de TEV, el uso de esteroides y el estado nutricional).CONCLUSIÓN:TEV hospitalaria en la cirugía abdominopélvica para la EII es una complicación mórbida infrecuente, pero costosa. Debido a la magnitud de la morbilidad el impacto económico, la prevención del TEV debería ser una prioridad de investigación y para mejoría de calidad a nivel nacional. Consulte Video Resumen en http://links.lww.com/DCR/B544.
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Persistently High Rate of Venous Thromboembolic Disease in Inflammatory Bowel Disease: A Population-Based Study. Am J Gastroenterol 2021; 116:1476-1484. [PMID: 33767104 DOI: 10.14309/ajg.0000000000001237] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 02/22/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Venous thromboembolism (VTE) is known to be increased in inflammatory bowel disease (IBD). We aimed to determine whether rates of VTE in IBD have reduced over the past 30 years. METHODS We used the population-based University of Manitoba IBD Epidemiology Database (1984-2018) to determine the incidence of VTE in IBD and the incidence rate ratio vs matched controls. In persons with IBD with and without VTE, we assessed for variables that were associated with an increased risk of VTE on multivariate logistic regression. RESULTS The incidence of VTE in the IBD cohort was 7.6% which was significantly greater than in controls (3.3%, P < 0.0001). The overall age-standardized incidence rate of VTE was 433 per 100,000 in IBD and 184 per 100,000 in controls. The incidence of VTE was higher in Crohn's disease (8.4%) than in ulcerative colitis (6.9%, P = 0.0028). The incidence rate ratio in IBD vs controls was 2.36 (95% confidence interval 2.16-2.58). The increased risk was similar in males and females and in Crohn's disease compared with ulcerative colitis. The incidence rate among persons with IBD from 1985 to 2018 decreased very slowly, with annual percent change of -0.7% (P = 0.0003). Hospital admission, high comorbidity, use of antibodies to tumor necrosis factor for less than 3 years up until the time of the VTE, and the combination of steroid and antibodies to tumor necrosis factor increased the risk of VTE. DISCUSSION Despite advancements in IBD management in the past 30 years, the rates of VTE have only been slowly decreasing and remain significantly increased compared with controls.
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