|
1
|
Kurpiewska D, Kośnik A, Bieliński K, Raszeja-Wyszomirska J. Beyond the Limits of Conventional Coagulation Tests: A Comprehensive Overview of ACLF-Related Coagulopathies. J Clin Med 2025; 14:3539. [PMID: 40429533 PMCID: PMC12112600 DOI: 10.3390/jcm14103539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2025] [Revised: 05/11/2025] [Accepted: 05/16/2025] [Indexed: 05/29/2025] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a complex and severe condition marked by multiple organ failure and high short-term mortality. Coagulopathy, a key component of ACLF, is characterized by rebalanced hemostasis with both hypo- and hypercoagulable features, increasing the risk of bleeding and thrombosis. Conventional coagulation tests, including prothrombin time (PT) and platelet count, fail to fully capture the complexity of coagulation dysfunction in ACLF. Advanced diagnostic tools, like viscoelastic tests (VETs), offer a more comprehensive assessment, yet they remain limited in evaluating endothelial dysfunction and fail to account for reduced levels of anticoagulant factors. Emerging therapeutic strategies targeting coagulopathies in ACLF hold promise, but their clinical efficacy remains unclear. A more nuanced approach to diagnosing and managing coagulopathy in ACLF is needed, incorporating advanced hemostatic profiling to better inform prognosis and guide treatment decisions.
Collapse
|
|
2
|
Thanapirom K, Suksawatamnuay S, Thaimai P, Ananchuensook P, Kijrattanakul P, Angchaisuksiri P, Tangkijvanich P, Treeprasertsuk S, Komolmit P. Association between Clot Waveform Analysis Parameters and the Severity of Liver Cirrhosis. Thromb Haemost 2025. [PMID: 39788529 DOI: 10.1055/a-2505-8616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
BACKGROUND Clot waveform analysis (CWA) provides a global assessment of hemostasis and may be useful for patients with cirrhosis with complex hemostatic abnormalities. This study aimed to assess the association between prothrombin time (PT-) and activated partial thromboplastin time (aPTT-) based CWA parameters and cirrhosis severity and prospectively evaluate the role of CWA in predicting mortality and acute decompensation (AD) over 1 year. METHODS This prospective study included adult patients with cirrhosis between June 2021 and December 2023 at Chulalongkorn University Hospital. The PT- and aPTT-based CWA parameters were obtained using an automated coagulation analyzer. RESULTS A total of 560 patients with cirrhosis were included; 165 (29.5%) and 47 (11.5%) had Child-Turcotte-Pugh (CTP) B and C cirrhosis, respectively. The PT- and aPTT-based CWA parameters, including maximum velocity (min1), maximum acceleration (min2), and maximum deceleration (max2), were significantly lower (p ≤ 0.05) in patients with decompensated cirrhosis than in those with compensated cirrhosis. Additionally, CWA values were significantly higher in patients with higher CTP and Model for End-Stage Liver Disease (MELD) scores. Multivariable analysis revealed that liver stiffness (LS) and max2 of PT-based CWA assay were independently associated with CTP B/C. In addition, min2 and max2 of PT-based CWA assay were independently associated with 1-year mortality. No significant differences in CWA parameters were observed between patients with and without portal vein thrombosis. CWA parameters were not related to AD during the 1-year follow-up. CONCLUSION A hypocoagulable profile based on CWA parameters is associated with advanced-stage cirrhosis. CWA may be a useful objective marker for assessing cirrhosis severity and predicting 1-year mortality.
Collapse
Affiliation(s)
- Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence in Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence in Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence in Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Prooksa Ananchuensook
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence in Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Pitiphong Kijrattanakul
- Division of Hospital and Ambulatory Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Pantep Angchaisuksiri
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Department of Biochemistry, Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence in Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| |
Collapse
|
|
3
|
Lisman T. Toward Rational Strategies for Prevention of Bleeding During Invasive Procedures in Patients With Cirrhosis. J Clin Exp Hepatol 2025; 15:102452. [PMID: 39678068 PMCID: PMC11636297 DOI: 10.1016/j.jceh.2024.102452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 11/05/2024] [Indexed: 12/17/2024] Open
Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| |
Collapse
|
|
4
|
Janko N, Majeed A, Commins I, Gow P, Kemp W, Roberts SK. Rotational thromboelastometry predicts future bleeding events in patients with cirrhosis. Scand J Gastroenterol 2024; 59:1062-1068. [PMID: 39010734 DOI: 10.1080/00365521.2024.2375591] [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: 02/28/2024] [Revised: 06/17/2024] [Accepted: 06/27/2024] [Indexed: 07/17/2024]
Abstract
BACKGROUND AND AIMS Patients with cirrhosis of the liver are in a delicate state of rebalanced haemostasis and are at risk of developing both bleeding and thrombotic complications. Conventional haemostatic tests are unable to predict bleeding and thrombosis in these patients. We aimed to explore the role of Rotational Thromboelastometry (ROTEM) in predicting bleeding and thrombotic events in patients with cirrhosis. METHODS We conducted a prospective cohort study of patients with cirrhosis at two metropolitan hospitals. All patients underwent ROTEM analysis and were then followed to record any bleeding and thrombotic events. Univariate and multivariate logistic regression analyses were performed to explore associations with bleeding and thrombotic events. RESULTS Nineteen of the 162 patients recruited experienced a bleeding event within one year of ROTEM analysis. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in patients who had a bleeding event, compared to those who did not (50 mm vs. 57 mm, p < 0.01 and 48 mm vs. 54 mm, p < 0.01, respectively). In addition, on univariate analysis, clotting time (CT) in the INTEM test was prolonged in the bleeding group (214 s vs. 198 s, p = 0.01). On multivariate analysis, only MCFEX was a significant predictor of bleeding events. In contrast, there was no association found between ROTEM parameters and development of thrombosis within a one-year period. CONCLUSIONS ROTEM may provide a useful tool in predicting future bleeding events in patients with cirrhosis. Larger studies are required to further validate this finding and explore its application in clinical practice.
Collapse
Affiliation(s)
- Natasha Janko
- Department of Gastroenterology, Alfred Health, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Isabella Commins
- Department of Gastroenterology, Alfred Health, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Paul Gow
- Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Health, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| |
Collapse
|
|
5
|
Maynard S, Marrinan E, Roberts L, Stanworth S. Does the Use of Viscoelastic Hemostatic Assays for Periprocedural Hemostasis Management in Liver Disease Improve Clinical Outcomes? Transfus Med Rev 2024; 38:150823. [PMID: 38616454 PMCID: PMC11464402 DOI: 10.1016/j.tmrv.2024.150823] [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: 12/01/2023] [Revised: 02/05/2024] [Accepted: 02/14/2024] [Indexed: 04/16/2024]
Abstract
Routine hemostasis parameters such as prothrombin time and fibrinogen are frequently abnormal in patients with chronic liver disease and have been demonstrated to be poor predictors for periprocedural bleeding. Alterations in procoagulant and anticoagulant factors in this population result in a state of rebalanced hemostasis, which is not reflected by routine hemostatic measures. Viscoelastic hemostatic assays (VHA) present a point of care measure of global hemostasis with an emerging role in guiding transfusion in the liver transplant setting. The potential role for VHA in guiding periprocedural transfusion is unknown. Here we critically appraise the available limited evidence on the use of VHA to guide prophylactic treatment in patients with cirrhosis undergoing procedures. We assess whether the impact of a VHA-guided approach improves clinical outcomes. Suggested areas for future research with a focus on clinically relevant outcomes, particularly periprocedural bleeding, are highlighted.
Collapse
Affiliation(s)
- Suzanne Maynard
- NIHR Blood and Transplant Research Unit in Data Driven Transfusion Practice, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Elizabeth Marrinan
- Institute of Pharmaceutical Sciences, King's College London, UK; Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.
| | - Lara Roberts
- Institute of Pharmaceutical Sciences, King's College London, UK; Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK
| | - Simon Stanworth
- NIHR Blood and Transplant Research Unit in Data Driven Transfusion Practice, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Department of Haematology and Transfusion Medicine, NHSBT and Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| |
Collapse
|
|
6
|
Reardon B, Pasalic L, Favaloro EJ. The Role of Viscoelastic Testing in Assessing Hemostasis: A Challenge to Standard Laboratory Assays? J Clin Med 2024; 13:3612. [PMID: 38930139 PMCID: PMC11205135 DOI: 10.3390/jcm13123612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 06/18/2024] [Accepted: 06/18/2024] [Indexed: 06/28/2024] Open
Abstract
Viscoelastic testing is increasingly being used in clinical and research settings to assess hemostasis. Indeed, there are potential situations in which viscoelastic testing is reportedly superior to standard routine laboratory testing for hemostasis. We report the current testing platforms and terminology, as well as providing a concise narrative review of the published evidence to guide its use in various clinical settings. Notably, there is increasing evidence of the potential utility of viscoelastic testing for assessment of direct oral anticoagulants, and bleeding associated with chronic liver disease, orthotopic liver transplantation, cardiac surgery, trauma, obstetrics and pediatrics.
Collapse
Affiliation(s)
- Benjamin Reardon
- School of Medicine and Public Health, Joint Medical Program, University of Newcastle, Callaghan, NSW 2145, Australia;
- Haematology Department, Calvary Mater Hospital Newcastle, Waratah, NSW 2298, Australia
| | - Leonardo Pasalic
- Haematology Department, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW 2145, Australia;
- Westmead Clinical School, University of Sydney, Westmead, NSW 2145, Australia
- Sydney Centres for Thrombosis and Haemostasis, Westmead Hospital, Westmead, NSW 2145, Australia
| | - Emmanuel J. Favaloro
- Haematology Department, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW 2145, Australia;
- Sydney Centres for Thrombosis and Haemostasis, Westmead Hospital, Westmead, NSW 2145, Australia
- School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW 2650, Australia
- School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia
| |
Collapse
|
|
7
|
Tiede A, Susen S, Lisman T. Acquired bleeding disorders. Haemophilia 2024; 30 Suppl 3:29-38. [PMID: 38562115 DOI: 10.1111/hae.14995] [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: 01/23/2024] [Revised: 03/06/2024] [Accepted: 03/06/2024] [Indexed: 04/04/2024]
Abstract
Acquired bleeding disorders can develop in previously healthy people irrespective of age or gender but are particularly common in patients with certain underlying conditions. Here, we review recent advances in the management of acquired haemophilia A (AHA), acquired von Willebrand syndrome (AVWS), and patients with hemostatic abnormalities due to chronic liver disease (CLD). Patients with AHA can now benefit from prophylaxis with emicizumab, a therapeutic antibody that mimics the function of activated coagulation factor VIII. The treatment of AVWS remains challenging in many situations and requires careful consideration of the underlying condition. Haemostatic abnormalities in CLD are often compensated by proportional reduction in pro and anti-haemostatic factors resulting in sustained or even increased thrombin generation. Consequently, bleeding in CLD is rarely caused by haemostatic failure and infusion of plasma or coagulation factor concentrates may not be effective.
Collapse
Affiliation(s)
- Andreas Tiede
- Department of Haematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | - Sophie Susen
- Hemostasis and Transfusion Department, University of Lille, Lille University Hospital, Lille, France
| | - Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| |
Collapse
|
|
8
|
Soucy-Proulx M, Kato H, Coeckelenbergh S, Naili Kortaia S, Herboulier L, Pittau G, Pham P, Lemoine A, Duranteau J, Roullet S. Sonorheometry Device Thresholds in Liver Transplantation: An Observational Retrospective Study. J Clin Med 2024; 13:696. [PMID: 38337389 PMCID: PMC10856129 DOI: 10.3390/jcm13030696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/17/2024] [Accepted: 01/18/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) remains a potentially haemorrhagic procedure whose perioperative bleeding and transfusion could be better monitored using point-of-care devices. Quantra® is a device based on sonorheometry to assess whole blood clot formation. Our aims were to describe Quantra® parameters during LT and to study their correlations with standard laboratory parameters, and to determine Quantra® cut-off values for thrombocytopenia, hypofibrinogenemia and coagulation factors' deficit. METHODS In 34 patients undergoing LT, blood samples were collected before surgical incision, 15 min after the beginning of the anhepatic phase, and 15 min after arterial revascularization of the graft. RESULTS Clotting time (CT) was well correlated with prothrombin (PT) ratio and activated partial thromboplastin time (aPTT) ratio. Platelet contribution to clot stiffness (PCS) was correlated with platelets (ρ = 0.82, p < 0.001) and fibrinogen contribution clot stiffness (FCS) with fibrinogen (Fg) (ρ = 0.74, p < 0.001). CT predicted a PT ratio < 30% with an area under the curve (AUC) of 0.93 (95% CI 0.87-0.98; p < 0.001). PCS predicted a platelet count < 50 G/L with an AUC of 0.87 (95% CI 0.76-0.98, p < 0.001). FCS predicted a Fg < 1.0, 1.2 or 1.5 g/L, with an AUC of 0.86 (95% CI 0.77-094, p < 0.001), 0.82 (95% CI 0.74-0.91, p < 0.001) and 0.88 (95% CI 0.82-0.95, p < 0.001), respectively. CONCLUSION Quantra® provides a rapid assessment of haemostasis during LT.
Collapse
Affiliation(s)
- Maxim Soucy-Proulx
- Service d’Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (M.S.-P.); (H.K.); (S.C.); (S.N.K.); (L.H.)
- Department of Anesthesiology, Centre Hospitalier de l’Université de Montréal, Montreal, QC H2X 0A9, Canada
| | - Hiromi Kato
- Service d’Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (M.S.-P.); (H.K.); (S.C.); (S.N.K.); (L.H.)
| | - Sean Coeckelenbergh
- Service d’Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (M.S.-P.); (H.K.); (S.C.); (S.N.K.); (L.H.)
- Outcomes Research Consortium, Cleveland, OH 44195, USA
| | - Salima Naili Kortaia
- Service d’Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (M.S.-P.); (H.K.); (S.C.); (S.N.K.); (L.H.)
| | - Laurence Herboulier
- Service d’Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (M.S.-P.); (H.K.); (S.C.); (S.N.K.); (L.H.)
| | - Gabriella Pittau
- Centre Hépato-Biliaire, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France;
| | - Patrick Pham
- Service de Biochimie et Oncogénétique, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (P.P.); (A.L.)
| | - Antoinette Lemoine
- Service de Biochimie et Oncogénétique, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (P.P.); (A.L.)
| | - Jacques Duranteau
- Department of Anesthesiology and Intensive Care, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94276 Le Kremlin-Bicêtre, France;
| | - Stéphanie Roullet
- Service d’Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique—Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France; (M.S.-P.); (H.K.); (S.C.); (S.N.K.); (L.H.)
- INSERM, Hémostase Inflammation Thrombose HITH U1176, Université Paris Saclay, 94276 Le Kremlin-Bicêtre, France
| |
Collapse
|
|
9
|
Lisman T. How to assess hemostasis in patients with severe liver disease. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2023; 2023:267-273. [PMID: 38066858 PMCID: PMC10727047 DOI: 10.1182/hematology.2023000479] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
Patients with advanced liver diseases frequently acquire profound alterations in their hemostatic system. Simultaneous changes in procoagulant and anticoagulant systems result in a reset in the hemostatic balance with a relatively neutral net effect, although there are notable hypocoagulable and hypercoagulable features in the hemostatic system in patients with liver disease. Laboratory and clinical studies have demonstrated that patients have a relatively well-preserved hemostatic system even though routine diagnostic tests of hemostasis (prothrombin time, platelet count) suggest a bleeding tendency. Routine diagnostic tests of hemostasis are unsuitable to assess the hemostatic status of patients with liver disease, as these tests are insensitive for the concurrent prohemostatic and antihemostatic changes in these patients. These tests are, however, frequently requested in patients with liver disease, as they are well established indicators of severity of liver disease. This paper will discuss commonly used diagnostic and research-type hemostatic tests and will outline how test results should be interpreted in patients with liver disease.
Collapse
Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| |
Collapse
|
|
10
|
Chadha R. Quantra: A step forward in intraoperative coagulation management, or just the same old test? Liver Transpl 2023; 29:1149-1150. [PMID: 37358481 DOI: 10.1097/lvt.0000000000000192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 06/13/2023] [Indexed: 06/27/2023]
Affiliation(s)
- Ryan Chadha
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Florida, Jacksonville, Florida, USA
| |
Collapse
|
|
11
|
Zanetto A, Simioni P. A step forward toward understanding the complex dynamics of coagulation in patients with cirrhosis. J Thromb Haemost 2023; 21:1426-1428. [PMID: 37179073 DOI: 10.1016/j.jtha.2023.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 05/15/2023]
Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale - Università Padova, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
| | - Paolo Simioni
- Department of Medicine, General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
| |
Collapse
|
|
12
|
Larsen JB, Hvas CL, Hvas AM. Modified Rotational Thromboelastometry Protocol Using Tissue Plasminogen Activator for Detection of Hypofibrinolysis and Hyperfibrinolysis. Methods Mol Biol 2023; 2663:763-773. [PMID: 37204751 DOI: 10.1007/978-1-0716-3175-1_51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Viscoelastic testing includes thromboelastography (TEG®) and thromboelastometry (ROTEM®) and is widely used in bleeding patients to detect hypocoagulability and guide transfusion therapy. However, the ability of standard viscoelastic tests to assess fibrinolytic capacity is limited. We here describe a modified ROTEM® protocol with addition of tissue plasminogen activator that can be used to identify hypofibrinolysis or hyperfibrinolysis.
Collapse
Affiliation(s)
- Julie Brogaard Larsen
- Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Christine Lodberg Hvas
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
| | - Anne-Mette Hvas
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| |
Collapse
|
|
13
|
Calvo A, Torrente MA, Görlinger K, Fernandez J, Reverter E, Vidal J, Tassies D, Colmenero J, Blasi A, Reverter JC. Haemostasis patterns in patients with acute-on-chronic liver failure and acute decompensation of cirrhosis including thromboelastometric tests with and without the addition of Protac: a pilot study. Thromb J 2022; 20:75. [PMID: 36510196 PMCID: PMC9744590 DOI: 10.1186/s12959-022-00438-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 12/05/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Thromboelastometry is considered the best method to assesses hemostasis in liver disease. Diagnostic performance could be improved by adding protein C activators such as thrombomodulin or Protac®. We assessed changes in ROTEM parameters after the addition of Protac® in patients with acute-on-chronic liver failure (ACLF), acute decompensation (AD), and healthy individuals (HI) to define different hemostasis patterns, considering standard and velocity ROTEM parameters, and assess whether Protac® can improve the definition of the pattern. METHODS Pre-test, we investigated whether diluted EXTEM reagent improved the effect of Protac® on the clotting time (CT)-ratio with and without Protac®. Ten ACLF and 20 AD patients and 21 HI were included in the main study. RESULTS Standard EXTEM was used in the main study. INTEM CFT, INTEM A5 (inverse), and INTEM TPI (inverse) were the parameters that best differentiated liver disease from HI (ROC AUC, 0.921, 0.906, and 0.928, respectively; all P-values < 0.001). Combining INTEM CFT with EXTEM LI60-ratio only slightly improved the diagnostic performance (ROC AUC, 0.948; P < 0.001). EXTEM LI60 and INTEM maxV-t were the parameters that best differentiated between ACLF and AD patients (ROC AUC, 0.743, P = 0.033; and 0.723, P = 0.050; respectively). Combining EXTEM LI60 + INTEM maxV-t moderately improved the diagnostic performance (ROC AUC, 0.81, P < 0.001). CONCLUSIONS ROTEM velocity, fibrinolysis parameters and the indices calculated improve the diagnosis in combination with standard parameters (e.g., CFT and A5). Ratios calculated with and without Protac® (e.g., EXTEM LI60-ratio) only slightly increased the diagnostic performance in discriminating hemostasis patterns.
Collapse
Affiliation(s)
- Andrea Calvo
- grid.5841.80000 0004 1937 0247Anaesthesiology and Critical Care Department, Hospital Clínic, Institute d’Investigacions Biomédica AgustPi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Miguel Angel Torrente
- grid.410458.c0000 0000 9635 9413Haematology Department, Hospital Clínic and University of Barcelona, Barcelona, Spain
| | - Klaus Görlinger
- grid.5718.b0000 0001 2187 5445Department of Anaesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany ,Medical Department, Tem Innovations GmbH, Munich, Germany
| | - Javier Fernandez
- grid.410458.c0000 0000 9635 9413Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) Y Ciber de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Liver Unit, Institut de Malalties Digestives I Metabòliques, Hospital Clínic and University of Barcelona, Barcelona, Spain
| | - Enric Reverter
- grid.410458.c0000 0000 9635 9413Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) Y Ciber de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Liver Unit, Institut de Malalties Digestives I Metabòliques, Hospital Clínic and University of Barcelona, Barcelona, Spain
| | - Julia Vidal
- grid.410458.c0000 0000 9635 9413Anaesthesiology Department, Hospital Clínic, Barcelona, Spain
| | - Dolors Tassies
- grid.410458.c0000 0000 9635 9413Haematology Department, Hospital Clínic and University of Barcelona, Barcelona, Spain
| | - Jordi Colmenero
- grid.410458.c0000 0000 9635 9413Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) Y Ciber de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Liver Unit, Institut de Malalties Digestives I Metabòliques, Hospital Clínic and University of Barcelona, Barcelona, Spain
| | - Annabel Blasi
- grid.10403.360000000091771775Anaesthesiology Department, Hospital Clínic and University of Barcelona, Spain, Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) Y Ciber de Enfermedades Hepáticas Y Digestivas (CIBEREHD), 08036 Barcelona, Spain
| | - Juan Carlos Reverter
- grid.410458.c0000 0000 9635 9413Haematology Department, Hospital Clínic and University of Barcelona, Barcelona, Spain
| |
Collapse
|
|
14
|
Wells M, Raja M, Rahman S. Point-of-care viscoelastic testing. BJA Educ 2022; 22:416-423. [PMID: 36304915 PMCID: PMC9596284 DOI: 10.1016/j.bjae.2022.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 07/04/2022] [Accepted: 07/12/2022] [Indexed: 10/31/2022] Open
Affiliation(s)
- M. Wells
- Barts Health NHS Trust, London, UK
| | - M. Raja
- Royal Free London NHS Foundation Trust, London, UK
| | - S. Rahman
- Royal Free London NHS Foundation Trust, London, UK
| |
Collapse
|
|
15
|
Seshadri A, Appelbaum R, Carmichael SP, Cuschieri J, Hoth J, Kaups KL, Kodadek L, Kutcher ME, Pathak A, Rappold J, Rudnick SR, Michetti CP. Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document. Trauma Surg Acute Care Open 2022; 7:e000936. [PMID: 35991906 PMCID: PMC9345092 DOI: 10.1136/tsaco-2022-000936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/20/2022] [Indexed: 11/04/2022] Open
Abstract
Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.
Collapse
Affiliation(s)
- Anupamaa Seshadri
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Rachel Appelbaum
- Department of Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Samuel P Carmichael
- Department of Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Joseph Cuschieri
- Department of Surgery, San Francisco General Hospital and Trauma Center, San Francisco, California, USA
| | - Jason Hoth
- Department of Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Krista L Kaups
- Department of Surgery, UCSF Fresno, Fresno, California, USA
| | - Lisa Kodadek
- Surgery, Yale University School of Medicine, New Haven, Connecticut, USA,Department of Surgery, Yale New Haven Hospital, New Haven, Connecticut, USA
| | - Matthew E Kutcher
- Surgery, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Abhijit Pathak
- Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
| | - Joseph Rappold
- Department of Surgery, Maine Medical Center, Portland, Oregon, USA
| | - Sean R Rudnick
- Department of Gastroenterology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | | |
Collapse
|
|
16
|
Biswas S, Vaishnav M, Pathak P, Gunjan D, Mahapatra SJ, Kedia S, Rout G, Thakur B, Nayak B, Kumar R. Effect of thrombocytopenia and platelet transfusion on outcomes of acute variceal bleeding in patients with chronic liver disease. World J Hepatol 2022; 14:1421-1437. [PMID: 36158909 PMCID: PMC9376768 DOI: 10.4254/wjh.v14.i7.1421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/13/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Platelet transfusion in acute variceal bleeding (AVB) is recommended by few guidelines and is common in routine clinical practice, even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear. AIM To determine how platelet counts, platelets transfusions, and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control, rebleeding, and mortality. METHODS Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB. The outcomes were assessed as the risk of rebleeding at days 5 and 42, and risk of death at day 42, considering the platelet counts and platelet transfusion. Propensity score matching (PSM) was used to compare the outcomes in those who received platelet transfusion. Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Cox-proportional hazard model for rebleeding and for 42-d mortality. RESULTS The study included 913 patients, with 83.5% men, median age 45 years, and Model for End-stage Liver Disease score 14.7. Platelet count < 20 × 109/L, 20-50 × 109/L, and > 50 × 109/L were found in 23 (2.5%), 168 (18.4%), and 722 (79.1%) patients, respectively. Rebleeding rates were similar between the three platelet groups on days 5 and 42 (13%, 6.5%, and 4.7%, respectively, on days 5, P = 0.150; and 21.7%, 17.3%, and 14.4%, respectively, on days 42, P = 0.433). At day 42, the mortality rates for the three platelet groups were also similar (13.0%, 23.2%, and 17.2%, respectively, P = 0.153). On PSM analysis patients receiving platelets transfusions (n = 89) had significantly higher rebleeding rates on day 5 (14.6% vs 4.5%; P = 0.039) and day 42 (32.6% vs 15.7%; P = 0.014), compared to those who didn't. The mortality rates were also higher among patients receiving platelets (25.8% vs 23.6%; P = 0.862), although the difference was not significant. On multivariate analysis, platelet transfusion and not platelet count, was independently associated with 42-d rebleeding. Hepatic encephalopathy was independently associated with 42-d mortality. CONCLUSION Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB; however, platelet transfusion increased rebleeding on days 5 and 42, with a higher but non-significant effect on mortality.
Collapse
Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Manas Vaishnav
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Piyush Pathak
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Soumya Jagannath Mahapatra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Gyanranjan Rout
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Bhaskar Thakur
- Division of Biostatistics, UT Southwestern Medical Center, Dallas, Texas 75390, United States
| | - Baibaswata Nayak
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 800014, Bihar, India
| |
Collapse
|
|
17
|
Lisman T, Caldwell SH, Intagliata NM. Haemostatic alterations and management of haemostasis in patients with cirrhosis. J Hepatol 2022; 76:1291-1305. [PMID: 35589251 DOI: 10.1016/j.jhep.2021.11.004] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/31/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022]
Abstract
Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic proteins. Although historically patients with cirrhosis were thought to have a haemostasis-related bleeding tendency, it is now widely accepted that the haemostatic system of patients with cirrhosis remains in balance as a result of simultaneous changes in pro- and anti-haemostatic systems. The concept of rebalanced haemostasis has led to changes in clinical management, although firm evidence from well-designed clinical studies is largely lacking. For example, many invasive procedures in patients with cirrhosis and a prolonged prothrombin time are now performed without prophylaxis with fresh frozen plasma. Conversely, clinicians have become more aware of the need for anti-thrombotic therapy, even in those patients with abnormal routine coagulation tests. This paper will outline recent advances in pathogenesis, prevention and treatment of both bleeding and thrombotic complications in patients with cirrhosis. Among other topics, we will discuss the haemostatic status of acutely ill patients with cirrhosis, the various causes of bleeding in patients with cirrhosis, and how best to prevent or treat bleeding. In addition, we will discuss the hypercoagulable features of patients with cirrhosis, new insights into the pathogenesis of portal vein thrombosis, and how best to prevent or treat thromboses.
Collapse
Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Coagulation in Liver Disease, University of Virginia Medical Center, Charlottesville VA, United States
| | - Nicolas M Intagliata
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Coagulation in Liver Disease, University of Virginia Medical Center, Charlottesville VA, United States
| |
Collapse
|
|
18
|
Malleeswaran S, Sivajothi S, Reddy MS. Viscoelastic Monitoring in Liver Transplantation. Liver Transpl 2022; 28:1090-1102. [PMID: 34724319 DOI: 10.1002/lt.26352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 10/21/2021] [Accepted: 10/27/2021] [Indexed: 12/13/2022]
Abstract
Cirrhosis and liver transplantation (LT) surgery are associated with substantial alterations to the patient's coagulation status. Accurate monitoring of these changes during LT can help manage bleeding proactively and potentially reduce transfusion requirements. Unlike conventional coagulation tests (CCTs), viscoelastic monitoring (VEM) can provide an accurate, real-time, point-of-care assessment of coagulation status during LT and hence has become an invaluable tool for anesthetists and intensive care physicians. However, it remains an enigmatic subject for transplantation surgeons who are more conversant with CCTs. This review discusses the principles of VEM, provides a primer to understanding and interpreting its output, and explains how it can be used to make real-world clinical decisions during LT.
Collapse
Affiliation(s)
- Selvakumar Malleeswaran
- Department of Liver Anesthesia and Critical Care, Institute of Liver Diseases and Transplantation, Gleneagles Global Health City, Chennai, India
| | - Sivanesan Sivajothi
- Department of Liver Anesthesia and Critical Care, Institute of Liver Diseases and Transplantation, Gleneagles Global Health City, Chennai, India
| | - Mettu Srinivas Reddy
- Department of Hepatobiliary Surgery and Liver Transplantation, Institute of Liver Diseases and Transplantation, Gleneagles Global Health City, Chennai, India
| |
Collapse
|
|
19
|
Villa E, Bianchini M, Blasi A, Denys A, Giannini EG, de Gottardi A, Lisman T, de Raucourt E, Ripoll C, Rautou PE. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol 2022; 76:1151-1184. [PMID: 35300861 DOI: 10.1016/j.jhep.2021.09.003] [Citation(s) in RCA: 182] [Impact Index Per Article: 60.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 09/13/2021] [Indexed: 12/11/2022]
Abstract
The prevention and management of bleeding and thrombosis in patients with cirrhosis poses several difficult clinical questions. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics, including current views on haemostasis in liver disease, controversy regarding the need to correct thrombocytopenia and abnormalities in the coagulation system in patients undergoing invasive procedures, and the need for thromboprophylaxis in hospitalised patients with haemostatic abnormalities. Multiple recommendations in this document are based on interventions that the panel feels are not useful, even though widely applied in clinical practice.
Collapse
|
|
20
|
van den Boom BP, Lisman T. Pathophysiology and management of bleeding and thrombosis in patients with liver disease. Int J Lab Hematol 2022; 44 Suppl 1:79-88. [PMID: 35446468 PMCID: PMC9540811 DOI: 10.1111/ijlh.13856] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/04/2022] [Accepted: 04/06/2022] [Indexed: 11/27/2022]
Abstract
Patients with liver disease often develop complex changes in their haemostatic system. Frequently observed changes include thrombocytopaenia and altered plasma levels of most of the proteins involved in haemostasis. Although liver disease was historically classified as a haemostasis‐related bleeding disorder, it has now been well established that the antihaemostatic changes that promote bleeding are compensated for by prohaemostatic changes. Conventional coagulation tests however do not accurately reflect these prohaemostatic changes, resulting in an underestimation of haemostatic potential. Novel coagulation tests, such as viscoelastic tests (VETs) and thrombin generation assays (TGAs) better reflect the net result of the haemostatic changes in patients with liver disease, and demonstrate a new, “rebalanced” haemostatic status. Although rebalanced, this haemostatic status is more fragile than in patients without liver disease. Patients with liver disease are therefore not only at risk of bleeding but also at risk of thrombosis. Notably, however, many haemostatic complications in liver disease are not related to the haemostatic failure. It is, therefore, crucial to identify the cause of the bleed or thrombotic complication in order to provide adequate treatment. In this paper, we will elaborate on the haemostatic changes that occur in liver disease, reflect on laboratory and clinical studies over the last few years, and explore the pathophysiologies of bleeding and thrombosis in this specific patient group.
Collapse
Affiliation(s)
- Bente P van den Boom
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| |
Collapse
|
|
21
|
Driever EG, Lisman T. Effects of Inflammation on Hemostasis in Acutely Ill Patients with Liver Disease. Semin Thromb Hemost 2022; 48:596-606. [PMID: 35135033 DOI: 10.1055/s-0042-1742438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Patients with liver diseases are in a rebalanced state of hemostasis, due to simultaneous decline in pro- and anticoagulant factors. This balance seems to remain even in the sickest patients, but is less stable and might destabilize when patients develop disease complications. Patients with acute decompensation of cirrhosis, acute-on-chronic liver failure, or acute liver failure often develop complications associated with changes in the hemostatic system, such as systemic inflammation. Systemic inflammation causes hemostatic alterations by adhesion and aggregation of platelets, release of von Willebrand factor (VWF), enhanced expression of tissue factor, inhibition of natural anticoagulant pathways, and inhibition of fibrinolysis. Laboratory tests of hemostasis in acutely-ill liver patients may indicate a hypocoagulable state (decreased platelet count, prolongations in prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels) due to decreased synthetic liver capacity or consumption, or a hypercoagulable state (increased VWF levels, hypofibrinolysis in global tests). Whether these changes are clinically relevant and should be corrected with antithrombotic drugs or blood products is incompletely understood. Inflammation and activation of coagulation may cause local ischemia, progression of liver disease, and multiorgan failure. Anti-inflammatory treatment in acutely-ill liver patients may be of potential interest to prevent thrombotic or bleeding complications and halt progression of liver disease.
Collapse
Affiliation(s)
- Ellen G Driever
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| |
Collapse
|
|
22
|
Nguyen G, Lejeune M, Crichi B, Frere C. Hemostasis testing in patients with liver dysfunction: Advantages and caveats. World J Gastroenterol 2021; 27:7285-7298. [PMID: 34876789 PMCID: PMC8611202 DOI: 10.3748/wjg.v27.i42.7285] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/08/2021] [Accepted: 10/20/2021] [Indexed: 02/06/2023] Open
Abstract
Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a “rebalanced hemostasis”, which can easily be tipped toward either a hypo- or a hypercoagulable phenotype. Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities. Conventional coagulation screening tests, such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures. The introduction of global coagulation assays, such as viscoelastic testing (VET), has been an important step forward in the assessment of the overall hemostasis profile. A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings. The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.
Collapse
Affiliation(s)
- Guillaume Nguyen
- Department of Hematology, Trousseau Hospital, Assistance Publique Hôpitaux de Paris, Paris 75012, France
| | - Manon Lejeune
- Department of Hematology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris 75013, France
| | - Benjamin Crichi
- Department of Internal Medicine, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris 75010, France
| | - Corinne Frere
- Department of Hematology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris 75013, France
- Inserm UMRS_1166, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris 75013, France
| |
Collapse
|
|
23
|
Hvas CL, Larsen JB, Adelborg K, Christensen S, Hvas AM. Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding-A Systematic Review and a Cohort Study. Semin Thromb Hemost 2021; 48:31-54. [PMID: 34715692 DOI: 10.1055/s-0041-1735454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3-4, and 7-8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin-antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis (n = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.
Collapse
Affiliation(s)
- Christine Lodberg Hvas
- Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Julie Brogaard Larsen
- Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Kasper Adelborg
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Steffen Christensen
- Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Anne-Mette Hvas
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
|
24
|
Campello E, Zanetto A, Bulato C, Maggiolo S, Spiezia L, Russo FP, Gavasso S, Mazzeo P, Tormene D, Burra P, Angeli P, Senzolo M, Simioni P. Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. Liver Int 2021; 41:2455-2466. [PMID: 34219335 PMCID: PMC8518681 DOI: 10.1111/liv.15001] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 06/26/2021] [Accepted: 06/30/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Understanding factors responsible for the increased bleeding tendency in acute-on-chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding. METHODS Cirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive haemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin-modified thrombin generation (TG) and thromboelastometry (ROTEM® ). In study part 1 (case-control), we compared coagulation in ACLF vs AD. In study part 2 (prospective), all patients were followed for bleeding, and predictors of outcome were assessed. RESULTS Ninety-one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and activated partial thrombin time were longer in ACLF cohort vs AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM® were significantly lower in ACLF, indicative of a more hypocoagulable state. No haemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not. CONCLUSION We found coagulation changes in ACLF to largely overlap with that of AD and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF; however, no correlation was found between such alterations and bleeding.
Collapse
Affiliation(s)
- Elena Campello
- Thrombotic and Hemorrhagic Diseases UnitGeneral Internal MedicinePadova University HospitalPadovaItaly
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant UnitDepartment of Surgery, Oncology, and GastroenterologyPadova University HospitalPadovaItaly
| | - Cristiana Bulato
- Thrombotic and Hemorrhagic Diseases UnitGeneral Internal MedicinePadova University HospitalPadovaItaly
| | - Sara Maggiolo
- Gastroenterology and Multivisceral Transplant UnitDepartment of Surgery, Oncology, and GastroenterologyPadova University HospitalPadovaItaly
- Liver Unit, V Chair of Internal MedicineDepartment of MedicinePadova University HospitalPadovaItaly
| | - Luca Spiezia
- Thrombotic and Hemorrhagic Diseases UnitGeneral Internal MedicinePadova University HospitalPadovaItaly
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant UnitDepartment of Surgery, Oncology, and GastroenterologyPadova University HospitalPadovaItaly
| | - Sabrina Gavasso
- Thrombotic and Hemorrhagic Diseases UnitGeneral Internal MedicinePadova University HospitalPadovaItaly
| | - Pierluigi Mazzeo
- Thrombotic and Hemorrhagic Diseases UnitGeneral Internal MedicinePadova University HospitalPadovaItaly
| | - Daniela Tormene
- Thrombotic and Hemorrhagic Diseases UnitGeneral Internal MedicinePadova University HospitalPadovaItaly
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant UnitDepartment of Surgery, Oncology, and GastroenterologyPadova University HospitalPadovaItaly
| | - Paolo Angeli
- Gastroenterology and Multivisceral Transplant UnitDepartment of Surgery, Oncology, and GastroenterologyPadova University HospitalPadovaItaly
- Liver Unit, V Chair of Internal MedicineDepartment of MedicinePadova University HospitalPadovaItaly
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant UnitDepartment of Surgery, Oncology, and GastroenterologyPadova University HospitalPadovaItaly
| | - Paolo Simioni
- Thrombotic and Hemorrhagic Diseases UnitGeneral Internal MedicinePadova University HospitalPadovaItaly
| |
Collapse
|
|
25
|
Stravitz RT, Fontana RJ, Meinzer C, Durkalski V, Hanje AJ, Olson J, Koch D, Hamid B, Schilsky ML, McGuire B, Ganger D, Liou I, Karvellas CJ, Rule JA, Lisman T, Clasen K, Reuben A, Cripps MW, Lee WM, ALF Study Group. Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure. Hepatology 2021; 74:937-949. [PMID: 33636020 PMCID: PMC10668528 DOI: 10.1002/hep.31767] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 02/01/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. APPROACH AND RESULTS A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109 /L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non-acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high-grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. CONCLUSIONS In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.
Collapse
Affiliation(s)
- RT Stravitz
- Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA
| | - RJ Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - C Meinzer
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - V Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - AJ Hanje
- Department of Medicine, The Ohio State University, Columbus, OH
| | - J Olson
- Division of Gastroenterology, University of Kansas Medical Center, Kansas City, KS
| | - D Koch
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - B Hamid
- Department of Medicine, University of California at San Francisco, San Francisco, CA
| | - ML Schilsky
- Divisions of Digestive Disease and Transplant and Immunology, Yale University, New Haven, CT
| | - B McGuire
- Division of Gastroenterology, University of Alabama, Birmingham, AL
| | - D Ganger
- Division of Gastroenterology, Northwestern University, Chicago, IL
| | - I Liou
- Department of Medicine, University of Washington, Seattle, WA
| | - CJ Karvellas
- Division of Gastroenterology (Liver Unit) and Department of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada
| | - JA Rule
- Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX
| | - T Lisman
- Department of Surgery, University of Groningen, Groningen, The Netherlands
| | - K Clasen
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - A Reuben
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - MW Cripps
- Department of Surgery, University of Texas, Southwestern Medical Center, Dallas, TX
| | - WM Lee
- Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX
| | | |
Collapse
|
|
26
|
Hvas CL, Hvas AM. Hemostasis and Fibrinolysis following Aneurysmal Subarachnoid Hemorrhage: A Systematic Review on Additional Knowledge from Dynamic Assays and Potential Treatment Targets. Semin Thromb Hemost 2021; 48:356-381. [PMID: 34261149 DOI: 10.1055/s-0041-1730346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Mortality after aneurysmal subarachnoid hemorrhage (aSAH) is augmented by rebleeding and delayed cerebral ischemia (DCI). A range of assays evaluating the dynamic process of blood coagulation, from activation of clotting factors to fibrinolysis, has emerged and a comprehensive review of hemostasis and fibrinolysis following aSAH may reveal targets of treatment. We conducted a systematic review of existing literature assessing coagulation and fibrinolysis following aSAH, but prior to treatment. PubMed, Embase, and Web of Science were searched on November 18, 2020, without time boundaries. In total, 45 original studies were eventually incorporated into this systematic review, divided into studies presenting data only from conventional or quantitative assays (n = 22) and studies employing dynamic assays (n = 23). Data from conventional or quantitative assays indicated increased platelet activation, whereas dynamic assays detected platelet dysfunction possibly related to an increased risk of rebleeding. Secondary hemostasis was activated in conventional, quantitative, and dynamic assays and this was related to poor neurological outcome and mortality. Studies systematically investigating fibrinolysis were sparse. Measurements from conventional or quantitative assays, as well as dynamic fibrinolysis assays, revealed conflicting results with normal or increased lysis and changes were not associated with outcome. In conclusion, dynamic assays were able to detect reduced platelet function, not revealed by conventional or quantitative assays. Activation of secondary hemostasis was found in both dynamic and nondynamic assays, while changes in fibrinolysis were not convincingly demonstrable in either dynamic or conventional or quantitative assays. Hence, from a mechanistic point of view, desmopressin to prevent rebleeding and heparin to prevent DCI may hold potential as therapeutic options. As changes in fibrinolysis were not convincingly demonstrated and not related to outcome, the use of tranexamic acid prior to aneurysm closure is not supported by this review.
Collapse
Affiliation(s)
- Christine Lodberg Hvas
- Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Anne-Mette Hvas
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
|
27
|
Northup PG, Lisman T, Roberts LN. Treatment of bleeding in patients with liver disease. J Thromb Haemost 2021; 19:1644-1652. [PMID: 33974330 PMCID: PMC8362012 DOI: 10.1111/jth.15364] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/16/2021] [Accepted: 05/06/2021] [Indexed: 12/14/2022]
Abstract
Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure-related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post-procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis.
Collapse
Affiliation(s)
- Patrick G. Northup
- Center for the Study of Hemostasis and Coagulation in Liver DiseaseDivision of Gastroenterology and HepatologyUniversity of VirginiaCharlottesvilleVAUSA
| | - Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Lara N. Roberts
- Department of Haematological MedicineKing’s Thrombosis CentreKing’s College Hospital National Health Service (NHS) Foundation TrustLondonUK
| |
Collapse
|
|
28
|
Larsen JB, Hvas AM. Fibrinolytic Alterations in Sepsis: Biomarkers and Future Treatment Targets. Semin Thromb Hemost 2021; 47:589-600. [PMID: 33878784 DOI: 10.1055/s-0041-1725096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Sepsis is a life-threatening condition which develops as a dysregulated immune response in the face of infection and which is associated with profound hemostatic disturbances and in the most extreme cases disseminated intravascular coagulation (DIC). In addition, the fibrinolytic system is subject to alterations during infection and sepsis, and impaired fibrinolysis is currently considered a key player in sepsis-related microthrombus formation and DIC. However, we still lack reliable biomarkers to assess fibrinolysis in the clinical setting. Furthermore, drugs targeting the fibrinolytic system have potential value in sepsis patients with severe fibrinolytic disturbances, but these are still being tested in the preclinical stage. The present review provides an overview of key fibrinolytic changes in sepsis, reviews the current literature on potential laboratory markers of altered fibrinolysis in adult sepsis patients, and discusses future perspectives for diagnosis and treatment of fibrinolytic disturbances in sepsis patients.
Collapse
Affiliation(s)
- Julie Brogaard Larsen
- Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Anne-Mette Hvas
- Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| |
Collapse
|
|
29
|
Lisman T, Hernandez‐Gea V, Magnusson M, Roberts L, Stanworth S, Thachil J, Tripodi A. The concept of rebalanced hemostasis in patients with liver disease: Communication from the ISTH SSC working group on hemostatic management of patients with liver disease. J Thromb Haemost 2021; 19:1116-1122. [PMID: 33792172 PMCID: PMC8252070 DOI: 10.1111/jth.15239] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/30/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022]
Abstract
Patients with liver diseases acquire complex alterations in their hemostatic system that may lead to abnormalities in routine diagnostic test of hemostasis. Thrombocytopenia, prolongations in the prothrombin time and activated partial thromboplastin time, and decreased plasma fibrinogen are common in patients with advanced liver disease. Historically, liver diseases therefore have been classified as an acquired bleeding disorder. Laboratory and clinical observations have demonstrated that although routine diagnostic tests of hemostasis suggest a hypocoagulable state, patients with liver disease also tend to develop thrombotic events. Overall, patients have commensurate changes in both pro- and antihemostatic pathways. This new hemostatic balance, however, appears much more fragile than the hemostatic balance in individuals with normal liver function, and patients with liver disease can readily experience both hemostasis-related bleeding and thrombotic events. These insights into the hemostatic balance in patients with liver disease have led to revised recommendations for clinical management of hemostasis. In 2020, an SSC working group within the ISTH has been founded with the aim to disseminate new concepts on prevention and treatment of bleeding and thrombosis in patients with liver disease. The current document will outline the hemostatic changes in patients with liver disease, the limitations of routine diagnostic tests of hemostasis, and the concept of rebalanced hemostasis.
Collapse
Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity of GroningenUniversity Medical Center GroningenGroningenthe Netherlands
| | - Virginia Hernandez‐Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital ClínicIDIBAPSUniversity of BarcelonaCentro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN‐Liver)BarcelonaSpain
| | - Maria Magnusson
- Clinical Chemistry and Blood Coagulation ResearchMMKDepartment of PediatricsCLINTECKarolinska InstitutetDepartment of HematologyKarolinska University HospitalStockholmSweden
| | - Lara Roberts
- King's Thrombosis CentreDepartment of Haematological MedicineKing's College HospitalLondonUK
| | - Simon Stanworth
- Transfusion MedicineNHS Blood and TransplantOxfordUK
- Department of HaematologyOxford University HospitalsNHS Foundation TrustOxfordUK
- Radcliffe Department of MedicineUniversity of Oxford and NIHR Oxford Biomedical Research Centre (Haematology)OxfordUK
| | - Jecko Thachil
- Department of HaematologyManchester Royal InfirmaryManchesterUK
| | - Armando Tripodi
- IRCCS Ca’ Granda Maggiore Hospital FoundationAngelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi VillaMilanoItaly
| |
Collapse
|
|
30
|
Al Moosawi M, Trudeau J, Smith T, Lefebvre A, Shih AW. ROTEM in the setting of liver transplant surgery reduces frozen plasma transfusion. Transfus Apher Sci 2021; 60:103125. [PMID: 33775554 DOI: 10.1016/j.transci.2021.103125] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/28/2021] [Accepted: 03/19/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND INR is traditionally used as a marker of clinical coagulopathy, but is suboptimal in liver disease patients due to rebalanced hemostasis and its ineffectiveness to predict bleeding. Rotational thromboelastometry (ROTEM) testing evaluates whole blood hemostasis, which may provide more accurate assessments with the EXTEM CT parameter than INR. Thus, in end-stage liver disease (ESLD) patients, we hypothesized that elevated INRs are associated with normal EXTEM CT values. METHODS A retrospective study assessing adult (>18) patients with ESLD and elevated INRs undergoing liver transplantation, was performed to assess correlations between INR and EXTEM CT. This included patients post-ROTEM implementation where all had pre-operative ROTEM testing; and patients up to one year pre-ROTEM implementation to compare transfusion utilization. Data abstracted also included patient demographics, coagulation testing results, liver disease etiology, and MELD score. RESULTS The study included 138 patients in the post-ROTEM group and 59 patients in the pre-ROTEM group. Normal EXTEM CT was observed in 95.3 % and 93 % of patients with INR of 1.3-1.8 and up to 3 respectively. There was no correlation between INR of 1.3-1.8 and EXTEM CT (⍴ = 0.239), and only moderate correlation was observed with higher INRs (⍴ = 0.617 with INRs >1.8). ROTEM-guided transfusion in liver transplant surgeries was associated with reduced plasma transfusion (OR 0.27, 95 % CI 0.12-0.58, p = 0.001) after adjusting for red cell utilization and coagulation testing. CONCLUSION Our study suggests ROTEM may be advantageous for evaluating coagulopathy in patients with liver disease and ROTEM-guided transfusion reduces plasma transfusion.
Collapse
Affiliation(s)
- Muntadhar Al Moosawi
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jacqueline Trudeau
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Tyler Smith
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada
| | - Alexandre Lefebvre
- Department of Cardiothoracic Anesthesiology, Copenhagen University Hospital, Copenhagen, Denmark
| | - Andrew W Shih
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.
| |
Collapse
|
|
31
|
Lisman T, Bernal W, Patel VC. Hemostatic balance in acute-on-chronic liver failure. J Thromb Haemost 2021; 19:869-870. [PMID: 33650250 DOI: 10.1111/jth.15192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 11/15/2020] [Indexed: 10/22/2022]
Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - William Bernal
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Vishal C Patel
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
- Institute of Hepatology London, Foundation for Liver Research, London, UK
- School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| |
Collapse
|
|
32
|
Northup PG, Garcia-Pagan JC, Garcia-Tsao G, Intagliata NM, Superina RA, Roberts LN, Lisman T, Valla DC. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73:366-413. [PMID: 33219529 DOI: 10.1002/hep.31646] [Citation(s) in RCA: 369] [Impact Index Per Article: 92.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022]
Affiliation(s)
- Patrick G Northup
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis in Liver Disease, University of Virginia, Charlottesville, VA
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.,Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver), Barcelona, Spain
| | - Guadalupe Garcia-Tsao
- Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT.,Veterans Administration Healthcare System, West Haven, CT
| | - Nicolas M Intagliata
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis in Liver Disease, University of Virginia, Charlottesville, VA
| | - Riccardo A Superina
- Department of Transplant Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Lara N Roberts
- Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation, Surgical Research Laboratory, Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Dominique C Valla
- Hepatology Service, Hospital Beaujon, Clichy, France.,Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver), Barcelona, Spain
| |
Collapse
|
|
33
|
Sakai T. Viscoelastic testing in liver transplantation. Transfusion 2020; 60 Suppl 6:S61-S69. [PMID: 33089935 DOI: 10.1111/trf.16077] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/19/2020] [Accepted: 06/19/2020] [Indexed: 01/24/2023]
Abstract
Despite the lack of large randomized clinical studies, viscoelastic tests (VETs) have been a critical armamentarium for hemostatic control in liver transplantation (LT) since the 1960s. Many transplant institutions have adopted VETs in their clinical practice. Several small-size randomized clinical trials on LT patients have suggested that VET-guided hemostatic treatment algorithms have led to decreased indications for and amounts of transfused blood products, especially fresh-frozen plasma, compared to standard laboratory-based hemostatic management. VETs have also been reported to offer insight into the diagnosis and prediction of LT patients' development of hypercoagulability-related morbidity and mortality. There is still a need for VET device-specific hemostatic algorithms in LT, and clinicians must take into account the tendency to underestimate the coagulation capacity of VETs in patients with end-stage liver disease where hemostasis is rebalanced.
Collapse
Affiliation(s)
- Tetsuro Sakai
- Department of Anesthesiology and Perioperative Medicine, UPMC (University of Pittsburgh Medical Center), Pittsburgh, Pennsylvania, USA
| |
Collapse
|