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1
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McKechnie T, Wang J, Springer JE, Gross PL, Forbes S, Eskicioglu C. Extended thromboprophylaxis following colorectal surgery in patients with inflammatory bowel disease: a comprehensive systematic clinical review. Colorectal Dis 2020; 22:663-678. [PMID: 31490000 DOI: 10.1111/codi.14853] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 08/14/2019] [Indexed: 12/12/2022]
Abstract
AIM Patients with inflammatory bowel disease (IBD) are at increased risk of postoperative venous thromboembolism (VTE) following major abdominal surgery. The pathogenesis is multifactorial and not fully understood. A combination of pathophysiology, patient and surgical risk factors increase the risk of postoperative VTE in these patients. Despite being at increased risk, IBD patients are not regularly prescribed extended pharmacological thromboprophylaxis following colorectal surgery. Currently, there is a paucity of evidence-based guidelines. Thus, the aim of this review is to evaluate the role of extended pharmacological thromboprophylaxis in IBD patients undergoing colorectal surgery. METHOD A search of Ovid Medline, EMBASE and PubMed databases was performed. A qualitative analysis was performed using 10 clinical questions developed by colorectal surgeons and a thrombosis haematologist. The Newcastle-Ottawa Scale was utilized to assess the quality of evidence. RESULTS A total of 1229 studies were identified, 38 of which met the final inclusion criteria (37 retrospective, one case-control). Rates of postoperative VTE ranged between 0.6% and 8.9%. Patient-specific risk factors for postoperative VTE included ulcerative colitis, increased age and obesity. Surgery-specific risk factors for postoperative VTE included open surgery, emergent surgery and ileostomy creation. Patients with IBD were more frequently at increased risk in the included studies for postoperative VTE than patients with colorectal cancer. The risk of bias assessment demonstrated low risk of bias in patient selection and comparability, with variable risk of bias in reported outcomes. CONCLUSION There is a lack of evidence regarding the use of extended pharmacological thromboprophylaxis in patients with IBD following colorectal surgery. As these patients are at heightened risk of postoperative VTE, future study and consideration of the use of extended pharmacological thromboprophylaxis is warranted.
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Affiliation(s)
- T McKechnie
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - J Wang
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - J E Springer
- Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - P L Gross
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - S Forbes
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - C Eskicioglu
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Surgery, McMaster University, Hamilton, Ontario, Canada
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Meher LK, Dalai SP, Panda S, Hui PK, Nayak S. Unusual Case of Cerebral Venous Sinus Thrombosis in Patient with Ulcerative Colitis in Remission. J Clin Diagn Res 2016; 10:OD35-6. [PMID: 27437291 DOI: 10.7860/jcdr/2016/20105.7883] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Accepted: 04/19/2016] [Indexed: 01/14/2023]
Abstract
Ulcerative colitis (UC) is an idiopathic autoimmune inflammatory disease of the gastrointestinal tract. Cerebral venous sinus thrombosis along with deep vein thrombosis, pulmonary embolism and arterial thrombosis have occasionally been reported as a complication in the active phase of UC being attributed to its pro-thrombotic state. This paper depicts a 38-year-old female with a history of UC in remission who developed sudden onset headache, blurring of vision and seizures. Subsequent diagnosis of cerebral venous sinus thrombosis was made with MRI venography and treated with low molecular weight heparin with complete resolution of symptoms. The highlights of this case underscore the importance of evaluating cerebral venous sinus thrombosis as a cause of acute onset neurological deterioration in a setting of inflammatory bowel disease. It also emphasizes on the hypothesis that the risk of venous thrombosis or other hypercoagulable states have no direct relationship with the disease activity or flare-up.
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Affiliation(s)
- Lalit Kumar Meher
- Professor, Department of Medicine, MKCG Medical College , Brahmapur, Odisha, India
| | - Siba Prasad Dalai
- Junior Resident, Department of Medicine, MKCG Medical College , Brahmapur, Odisha, India
| | - Sameer Panda
- Junior Resident, Department of Medicine, MKCG Medical College , Brahmapur, Odisha, India
| | - Pankaj Kumar Hui
- Associate Professor, Department of Medicine, MKCG Medical College , Brahmapur, Odisha, India
| | - Sachidananda Nayak
- Assistant Professor, Department of Medicine, MKCG Medical College , Brahmapur, Odisha, India
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3
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Gan GH, Yang LM, Wang J. Thrombotic mechanism and anticoagulant therapy in inflammatory bowel disease patients. Shijie Huaren Xiaohua Zazhi 2016; 24:236-241. [DOI: 10.11569/wcjd.v24.i2.236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Thromboembolism (TE) in inflammatory bowel disease (IBD) is an increasingly noted extra-intestinal manifestation with high morbidity (about 1%-8%), and the incidence rate can reach 41% by mucosal biopsy. Although TE is a life-threatening complication of IBD, this complication is often overlooked. To date, the mechanism behind this prothrombotic state encountered in IBD patients is not fully understood, and it is multifactorial and related to the inflammatory state. In this review, we provide an overview of the current understanding of thrombotic mechanism and anticoagulant therapy in IBD. While controlling the activity of the disease with appropriate therapy, thromboembolism prophylaxis should be considered.
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Giannotta M, Tapete G, Emmi G, Silvestri E, Milla M. Thrombosis in inflammatory bowel diseases: what's the link? Thromb J 2015; 13:14. [PMID: 25866483 PMCID: PMC4393581 DOI: 10.1186/s12959-015-0044-2] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 02/26/2015] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease affects more than 2 million people in Europe, with almost 20% of patients being diagnosed in pediatric age. Patients with inflammatory bowel disease are at increased risk of thromboembolic complications which may affect patients’ morbidity and mortality. The risk of the most common thromboembolic events, such as deep venous thrombosis and pulmonary embolism, are estimated to be three-fold increased compared to controls, but many other districts can be affected. Moreover, patients with ulcerative colitis and Crohn’s disease experience thromboembolic events at a younger age compared to general population. Many factors have been investigated as determinants of the pro-thrombotic tendency such as acquired risk factors or genetic and immune abnormalities, but a unique cause has not been found. Many efforts have been focused on the study of abnormalities in the coagulation cascade, its natural inhibitors and the fibrinolytic system components and both quantitative and qualitative alterations have been demonstrated. Recently the role of platelets and microvascular endothelium has been reviewed, as the possible link between the inflammatory and hemostatic process.
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Affiliation(s)
- Martina Giannotta
- Gastroenterology Department, AOU Careggi Regional Referral Center for Inflammatory Bowel Disease, Florence, Italy
| | - Gherardo Tapete
- Gastroenterology Department, AOU Careggi Regional Referral Center for Inflammatory Bowel Disease, Florence, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence and Patologia Medica Unit, AOU Careggi, Florence, Italy
| | - Elena Silvestri
- Department of Experimental and Clinical Medicine, University of Florence and Patologia Medica Unit, AOU Careggi, Florence, Italy
| | - Monica Milla
- Gastroenterology Department, AOU Careggi Regional Referral Center for Inflammatory Bowel Disease, Florence, Italy
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Zezos P, Kouklakis G, Saibil F. Inflammatory bowel disease and thromboembolism. World J Gastroenterol 2014; 20:13863-13878. [PMID: 25320522 PMCID: PMC4194568 DOI: 10.3748/wjg.v20.i38.13863] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 05/24/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians' awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients.
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6
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Bouma G, Baggen JM, van Bodegraven AA, Mulder CJJ, Kraal G, Zwiers A, Horrevoets AJ, van der Pouw Kraan CTM. Thiopurine treatment in patients with Crohn's disease leads to a selective reduction of an effector cytotoxic gene expression signature revealed by whole-genome expression profiling. Mol Immunol 2013; 54:472-81. [PMID: 23454163 DOI: 10.1016/j.molimm.2013.01.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Revised: 01/16/2013] [Accepted: 01/21/2013] [Indexed: 12/30/2022]
Abstract
Crohn's disease (CD) is characterized by chronic inflammation of the gastrointestinal tract, as a result of aberrant activation of the innate immune system through TLR stimulation by bacterial products. The conventional immunosuppressive thiopurine derivatives (azathioprine and mercaptopurine) are used to treat CD. The effects of thiopurines on circulating immune cells and TLR responsiveness are unknown. To obtain a global view of affected gene expression of the immune system in CD patients and the treatment effect of thiopurine derivatives, we performed genome-wide transcriptome analysis on whole blood samples from 20 CD patients in remission, of which 10 patients received thiopurine treatment, compared to 16 healthy controls, before and after TLR4 stimulation with LPS. Several immune abnormalities were observed, including increased baseline interferon activity, while baseline expression of ribosomal genes was reduced. After LPS stimulation, CD patients showed reduced cytokine and chemokine expression. None of these effects were related to treatment. Strikingly, only one highly correlated set of 69 genes was affected by treatment, not influenced by LPS stimulation and consisted of genes reminiscent of effector cytotoxic NK cells. The most reduced cytotoxicity-related gene in CD was the cell surface marker CD160. Concordantly, we could demonstrate an in vivo reduction of circulating CD160(+)CD3(-)CD8(-) cells in CD patients after treatment with thiopurine derivatives in an independent cohort. In conclusion, using genome-wide profiling, we identified a disturbed immune activation status in peripheral blood cells from CD patients and a clear treatment effect of thiopurine derivatives selectively affecting effector cytotoxic CD160-positive cells.
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Affiliation(s)
- G Bouma
- VU University Medical Center, Deptartment of Gastroenterology, Amsterdam, The Netherlands
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7
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Wu X, Zhang W, Li JY, Chai BX, Peng J, Wang H, Mulholland MW. Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus. Neurogastroenterol Motil 2011; 23:279-85, e123-4. [PMID: 21143557 PMCID: PMC3079207 DOI: 10.1111/j.1365-2982.2010.01641.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND A previous study demonstrated the presence of protease-activated receptor (PAR) 1 and 2 in the dorsal motor nucleus of vagus (DMV). The aim of this study is to characterize the effect of thrombin on the apoptosis of DMV neurons. METHODS The dorsal motor nucleus of vagus neurons were isolated from neonatal rat brainstems using micro-dissection and enzymatic digestion and cultured. Apoptosis of DMV neurons were examined in cultured neurons. Apoptotic neuron was examined by TUNEL and ELISA. Data were analyzed using anova and Student's t-test. KEY RESULTS Exposure of cultured DMV neurons to thrombin (0.1 to 10 U mL(-1)) for 24 h significantly increased apoptosis. Pretreatment of DMV neurons with hirudin attenuated the apoptotic effect of thrombin. Similar induction of apoptosis was observed for the PAR1 receptor agonist SFLLR, but not for the PAR3 agonist TFRGAP, nor for the PAR4 agonist YAPGKF. Protease-activated receptors 1 receptor antagonist Mpr(Cha) abolished the apoptotic effect of thrombin, while YPGKF, a specific antagonist for PAR4, demonstrated no effect. After administration of thrombin, phosphorylation of JNK and P38 occurred as early as 15 min, and remained elevated for up to 45 min. Pretreatment of DMV neurons with SP600125, a specific inhibitor for JNK, or SB203580, a specific inhibitor for P38, significantly inhibited apoptosis induced by thrombin. CONCLUSIONS & INFERENCES Thrombin induces apoptosis in DMV neurons through a mechanism involving the JNK and P38 signaling pathways.
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Affiliation(s)
- Xiaobin Wu
- Department of Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Weizhen Zhang
- Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Ji-Yao Li
- Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Biao-Xin Chai
- Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Junsheng Peng
- Department of Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hui Wang
- Department of Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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8
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Casella G, Villanacci V, Di Bella C, Antonelli E, Baldini V, Bassotti G. Pulmonary diseases associated with inflammatory bowel diseases. J Crohns Colitis 2010; 4:384-389. [PMID: 21122533 DOI: 10.1016/j.crohns.2010.02.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2009] [Revised: 01/25/2010] [Accepted: 02/17/2010] [Indexed: 02/08/2023]
Abstract
Among the extra-intestinal manifestations of inflammatory bowel diseases, those involving the lung are relatively rare. However, there is a wide array of such manifestations, spanning from drug-related pathologies to airway disease, fistulas, granulomatous diseases, autoimmune and thromboembolic disorders. Although infrequent, people dealing with inflammatory bowel diseases must be aware of these conditions, sometimes life-threatening, to avoid further impairment of the health status of the patients and to alleviate their symptoms by prompt recognition and treatment.
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9
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Saibeni S, Saladino V, Chantarangkul V, Villa F, Bruno S, Vecchi M, de Franchis R, Sei C, Tripodi A. Increased thrombin generation in inflammatory bowel diseases. Thromb Res 2010; 125:278-82. [DOI: 10.1016/j.thromres.2009.10.012] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2009] [Revised: 10/19/2009] [Accepted: 10/21/2009] [Indexed: 12/19/2022]
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10
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De Cruz P, Lust M, Trost N, Wall A, Gerraty R, Connell WR. Cerebral venous thrombosis associated with ulcerative colitis. Intern Med J 2008; 38:865-7. [DOI: 10.1111/j.1445-5994.2008.01749.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Maher MM, Soloma SH. Assessment of thrombophilic abnormalities during the active state of inflammatory bowel disease. Saudi J Gastroenterol 2008; 14:192-7. [PMID: 19568537 PMCID: PMC2702936 DOI: 10.4103/1319-3767.41743] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2007] [Accepted: 05/12/2008] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS Thromboembolic disease has been recognized as a complication of inflammatory bowel disease (IBD). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency are unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously. The aim of this study was to investigate common thrombophilic markers in patients with active IBD. METHODS Twenty-six patients with IBD who had active disease, and 40 sex- and age-matched non-IBD patients were recruited into the study. For all the subjects, complete blood counts, C-reactive protein levels, erythrocyte sedimentation rate, International normalized ratio, activated partial thromboplastin time, and levels of lupus anticoagulant, anticardiolipin antibodies (ACA IgG), proteins C and S, antithrombin-III (AT-III), and factor V were measured. RESULTS The International normalized ratio, activated partial thromboplastin time, and levels of proteins C and S were comparable between the two groups. However, antithrombin-III levels were significantly lower in the IBD group as compared with that in the healthy control group (P < 0.001). ACA IgG was detected in one patient in the IBD group. Factor V Leiden mutation was present in 3.8% of the patients in the IBD group, whereas the prevalence was 2.5% in the control group. Significantly elevated platelet counts were observed in patients with active Crohn's disease compared with that in the control group (P < 0.001), but they were not significantly increased in active ulcerative colitis (P = 0.231). CONCLUSIONS The present study failed to establish a strong association between the common thrombophilic markers and the active clinical course of IBD, with the exception of high platelet counts and lower levels of AT-III in the IBD group as compared with those in the control group. All other parameters of thrombophilia were comparable between the two groups.
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Affiliation(s)
- Maha M. Maher
- Departments of Internal Medicine and Clinical Pathology, Mansoura and Al-Azhar University, Cairo, Egypt,Address: Dr. Maha Mohammed Maher, Associate Professor, Gastroenterology, Faculty of Medicine, Female section-King Faisal University, P.O.Box 1164, Hofuf, Al-Hassa 31982, Kingdom of Saudi Arabia. E-mail:
| | - Somaya H. Soloma
- Departments of Internal Medicine and Clinical Pathology, Mansoura and Al-Azhar University, Cairo, Egypt
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Abstract
In both Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), an increased risk of thrombotic events has been demonstrated. Pathogenesis of thrombosis is multifactorial as various primary coagulation system abnormalities other than acquired factors have been reported. The fibrinolytic system has been widely investigated in IBD. Most of the available data report an imbalance in fibrinolytic capacity with a tendency toward a hypofibrinolytic state. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 are fundamental inhibitors of the fibrinolytic process and are also considered to be acute-phase reactants. Recent studies have shown an imbalance of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, suggesting that these molecules might contribute to thromboembolic events in both forms of IBD.
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13
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Tsiolakidou G, Koutroubakis IE. Thrombosis and inflammatory bowel disease-the role of genetic risk factors. World J Gastroenterol 2008; 14:4440-4. [PMID: 18680221 PMCID: PMC2731268 DOI: 10.3748/wjg.14.4440] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD, which is developed as the result of multiple interactions between acquired and genetic risk factors. There is evidence indicating an imbalance of procoagulant, anticoagulant and fibrinolytic factors predisposing in thrombosis in patients with IBD. The genetic factors that have been suggested to interfere in the thrombotic manifestations of IBD include factor V Leiden, factor II (prothrombin, G20210A), methylenetetrahydrofolate reductase gene mutation (MTHFR, 6777T), plasminogen activator inhibitor type 1 (PAI-1) gene mutation and factor XIII (val34leu). In this article we review the current data and future prospects on the role of genetic risk factors in the development of thromboembolism in IBD.
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Shen J, Ran ZH, Zhang Y, Cai Q, Yin HM, Zhou XT, Xiao SD. Biomarkers of altered coagulation and fibrinolysis as measures of disease activity in active inflammatory bowel disease: a gender-stratified, cohort analysis. Thromb Res 2008; 123:604-11. [PMID: 18499234 DOI: 10.1016/j.thromres.2008.04.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2007] [Revised: 02/24/2008] [Accepted: 04/07/2008] [Indexed: 01/15/2023]
Abstract
BACKGROUND Growing evidence recognizes inflammatory bowel disease (IBD) as a chronic inflammatory condition characterized by a hypercoagulable state and prothrombotic conditions. The aims of our study were to evaluate the abnormalities in coagulation and fibrinolysis status in patients with IBD, and to analyze parameters of altered coagulation and fibrinolysis status which can correlated with and predict inflammatory parameters of disease activity. METHODS A cohort of 271 consecutive IBD patients was compared with healthy controls for coagulation and fibrinolysis status. Associations between altered coagulation and fibrinolysis status stratified by gender and inflammatory parameters were analyzed. RESULTS The mean levels of platelet, platelet distribution width, prothrombin time, fibrinogen, activated partial thromboplastin time were significantly higher in IBD patients than in healthy controls (all P<0.05). Mean platelet volume was lower in male patients with IBD than in healthy controls (P<0.01). Furthermore, multiple linear regression indicated that fibrinogen was an independent predictor of ESR (beta=1.316, P=<0.001) and CRP (beta=1.233, P=0.015) in male patients with active ulcerative colitis. Platelet (beta=0.436, P=0.037) and prothrombin time (beta=0.810, P=<0.001) were predictors of Crohn's Disease Activity Index in female patients with Crohn's disease. CONCLUSIONS To our knowledge, this study provides characteristics on altered coagulation and fibrinolysis status in active IBD patients using the largest number of cases assembled in one study to date. Our data suggest that in IBD patients, abnormalities in coagulation and fibrinolysis status were associated with disease activity. Fibrinogen, platelet and prothrombin time were predictors of inflammation.
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Affiliation(s)
- Jun Shen
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China
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15
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Anthoni C, Russell J, Wood KC, Stokes KY, Vowinkel T, Kirchhofer D, Granger DN. Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis. ACTA ACUST UNITED AC 2007; 204:1595-601. [PMID: 17562818 PMCID: PMC2118639 DOI: 10.1084/jem.20062354] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
There is growing evidence for an interplay between inflammatory and coagulation pathways in acute and chronic inflammatory diseases. However, it remains unclear whether components of the coagulation pathway, such as tissue factor (TF), contribute to intestinal inflammation, and whether targeting TF will blunt the inflammatory cell recruitment, tissue injury, and enhanced thrombus formation that occur in experimental colitis. Mice were fed 3% dextran sodium sulfate (DSS) to induce colonic inflammation, with some mice receiving a mouse TF-blocking antibody (muTF-Ab). The adhesion of leukocytes and platelets in colonic venules, light/dye-induced thrombus formation in cremaster muscle microvessels, as well as disease activity index, thrombin-antithrombin (TAT) complexes in plasma, and histopathologic changes in the colonic mucosa were monitored in untreated and muTF-Ab-treated colitic mice. In untreated mice, DSS elicited the recruitment of adherent leukocytes and platelets in colonic venules, caused gross and histologic injury, increased plasma TAT complexes, and enhanced thrombus formation in muscle arterioles. muTF-Ab prevented elevation in TAT complexes, reduced blood cell recruitment and tissue injury, and blunted thrombus formation in DSS colitic mice. These findings implicate TF in intestinal inflammation and support an interaction between inflammation and coagulation in experimental colitis.
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Affiliation(s)
- Christoph Anthoni
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
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16
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Danese S, Papa A, Saibeni S, Repici A, Malesci A, Vecchi M. Inflammation and coagulation in inflammatory bowel disease: The clot thickens. Am J Gastroenterol 2007; 102:174-86. [PMID: 17100967 DOI: 10.1111/j.1572-0241.2006.00943.x] [Citation(s) in RCA: 276] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Inflammation and coagulation play crucial roles in the pathogenesis of multiple chronic inflammatory disorders. Growing evidence highlights a tight mutual network in which inflammation, coagulation, and fibrinolysis play closely related roles. Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), are chronic inflammatory conditions, characterized by a hypercoagulable state and prothrombotic conditions, and accompanied by abnormalities in coagulation. From a pathophysiological point of view, cells and molecules classically implicated in the physiological process of coagulation have now been shown to behave abnormally in IBD and possibly to also play an active role in disease pathogenesis and/or disease progression. This paper reviews studies performed on the coagulation profile and risk factors for thrombosis in IBD. In particular, an overview is provided of the epidemiology, clinical features, and etiology of thromboembolic complications in IBD. Furthermore, we review hemostatic abnormalities in IBD, as well as the cell types involved in such processes. Finally, we highlight the coagulation system as a dynamic participant in the multifaceted process of chronic intestinal inflammation. Overall, an overview is provided that the coagulation system represents an important, though previously underestimated, component of IBD pathogenesis, and may be a possible target for therapeutic intervention.
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Affiliation(s)
- Silvio Danese
- Division of Gastroenterology, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy
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17
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Jay Wiesen A, Kurtz LE, Katz S. Widespread occlusive vascular disease in a Crohn's disease patient with profound thrombocytosis. J Clin Gastroenterol 2006; 40:863-4. [PMID: 17016147 DOI: 10.1097/01.mcg.0000225544.88632.1b] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Zezos P, Papaioannou G, Nikolaidis N, Patsiaoura K, Papageorgiou A, Vassiliadis T, Giouleme O, Evgenidis N. Low-molecular-weight heparin (enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis: a randomized, controlled, comparative study. Aliment Pharmacol Ther 2006; 23:1443-53. [PMID: 16669959 DOI: 10.1111/j.1365-2036.2006.02870.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Heparin could be beneficial to the treatment of active ulcerative colitis because of its anticoagulant, anti-inflammatory and immunomodulatory properties. AIM To evaluate the tolerability, safety and efficacy of low-molecular-weight heparin as adjuvant therapy in patients with active ulcerative colitis. METHODS Thirty-four adult patients with active ulcerative colitis were consecutively included in a prospective, randomized, comparative study, and were treated for 12 weeks. Eighteen patients in the 'standard therapy' group were treated with aminosalicylates and weekly tapered corticosteroids. Sixteen patients in the 'heparin therapy' group were treated with standard therapy plus enoxaparin 100 Anti-Xa IU/kg/day subcutaneously. RESULTS Seventeen patients in the 'standard therapy' group and 15 patients in the 'heparin therapy' group completed the study. Tolerability and compliance to therapy were excellent and no withdrawals were noted because of complications. There was a significant improvement in the disease severity in both groups (P<0.001), without any difference between them (P=not significant). Both treatment groups showed similar proportions of disease improvement (65% and 73%, respectively; P=not significant). There were no significant differences in inflammation (fibrinogen, ESR, CRP) and coagulation (thrombin-antithrombin complex, F1+2, D-dimers) parameters during and at the end of the study between treatment groups. CONCLUSION Adjuvant administration of low-molecular heparin in patients with active ulcerative colitis is safe and well tolerated, but no additive benefit over standard therapy for ulcerative colitis was noted.
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Affiliation(s)
- P Zezos
- 2nd Propaedeutic Department of Internal Medicine, Division of Gastroenterology, 'Hippokration' General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
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Koutroubakis IE. Therapy insight: Vascular complications in patients with inflammatory bowel disease. ACTA ACUST UNITED AC 2005; 2:266-72. [PMID: 16265230 DOI: 10.1038/ncpgasthep0190] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2005] [Accepted: 05/03/2005] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) is associated with an increased risk of vascular complications. The most important of these complications are arterial and venous thromboembolism, which represent a significant cause of morbidity and mortality in IBD patients. Recent data suggest that thromboembolism is a disease-specific extraintestinal manifestation of IBD. The most common thrombotic manifestations in IBD are deep vein thrombosis of the leg and pulmonary emboli. It has been suggested that disease activity and the extent of colonic localization are correlated with the risk of developing thromboembolism. The occurrence of thrombosis in patients with IBD is partially attributed to the existing hypercoagulable state in IBD. Both coagulation and fibrinolysis are activated in patients with IBD; this is especially true for those with active disease. The most common risk factors for thrombophilia in IBD patients with venous thromboembolism are Leiden mutation in the gene encoding factor V, hyperhomocysteinemia, and antiphospholipid antibodies. The main genetic defects that have been established as risk factors for venous thrombosis are rather uncommon in IBD, but when present increase the risk of thromboembolism. Screening for coagulation defects seems justified only in IBD patients with a history of thrombosis or a family history of venous thromboembolic events. Antithrombotic treatment of IBD patients with venous thromboembolism is similar to that of thrombotic non-IBD patients.
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Umit H, Asil T, Celik Y, Tezel A, Dokmeci G, Tuncbilek N, Utku U, Soylu AR. Cerebral sinus thrombosis in patients with inflammatory bowel disease: A case report. World J Gastroenterol 2005; 11:5404-7. [PMID: 16149158 PMCID: PMC4622821 DOI: 10.3748/wjg.v11.i34.5404] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the gastrointestinal tract. The pathophysiology of IBD is probably the result of the complex interaction of genetic susceptibility and environmental influences. There is a well-known risk of thrombosis in patients with IBD. We present the case of a 53-year-old man with ulcerative colitis, who spontaneously developed intracranial sinus thrombosis that was treated with low molecular weight heparin. Literature was searched to assess the frequency and characteristics of cerebral sinus thrombosis in IBD and the role of certain etiopathological factors in such thrombotic patients.
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Affiliation(s)
- Hasan Umit
- Trakya Universitesi Typ Fakültesi, Gastroenteroloji BD, Gullapoglu Yerleskesi, Edirne 22030, Turkey.
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