VWF/ADAMTS13 Imbalance, But Not Global Coagulation or Fibrinolysis, Is Associated With Outcome and Bleeding in Acute Liver Failure
Autor: | William M. Lee, Jingwen Zhang, Ellen G. Driever, Jelle Adelmeijer, Valerie Durkalski, R. Todd Stravitz, Ton Lisman |
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Přispěvatelé: | Groningen Institute for Organ Transplantation (GIOT) |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
Male medicine.medical_specialty VON-WILLEBRAND-FACTOR Liver Failure Cirrhosis and Portal Hypertension medicine.medical_treatment ADAMTS13 Protein REBALANCED HEMOSTASIS Hemorrhage Liver transplantation Gastroenterology DISEASE Von Willebrand factor Internal medicine hemic and lymphatic diseases von Willebrand Factor Fibrinolysis medicine Coagulopathy INJURY Humans International Normalized Ratio Blood Coagulation Hepatic encephalopathy RISK Hepatology biology business.industry Liver Diseases Patient Acuity Original Articles Liver Failure Acute medicine.disease ADAMTS13 Coagulation Case-Control Studies Hemostasis SAFETY biology.protein Female Original Article business SYSTEM |
Zdroj: | Hepatology, 73(5), 1882-1891. Wiley Hepatology (Baltimore, Md.) |
ISSN: | 0270-9139 |
Popis: | Background and Aims Recent studies of acute liver failure (ALF) in man and animals have suggested that rebalanced hemostasis occurs, with distinct hypercoagulable features clinically evidenced by a low risk of bleeding. Rodent models have shown a link between intrahepatic microthrombus formation and progression of ALF. We sought to confirm these earlier findings in a large series of patients with well-characterized ALF from the Acute Liver Failure Study Group.Approach and Results Citrated plasma samples taken on admission from 676 patients with ALF or acute liver injury (international normalized ratio >= 2.0 without hepatic encephalopathy) were used to determine levels of von Willebrand factor (VWF), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity, thrombomodulin-modified thrombin generation, and clot lysis time (CLT) and compared with the levels in 40 healthy controls. Patients had 3-fold increased VWF levels, 4-fold decreased ADAMTS13 activity, similar thrombin generating capacity, and 2.4-fold increased CLT, compared with controls. Increasing disease severity was associated with progressively more elevated VWF levels as well as hypofibrinolysis. Patients who died or underwent liver transplantation within 21 days of admission had higher VWF levels, lower ADAMTS13 activity, but similar thrombin generation and a similar proportion of patients with severe hypofibrinolysis, when compared with transplant-free survivors. Likewise, patients with bleeding complications had higher VWF levels and lower ADAMTS13 activity compared to those without bleeding. Thrombin generation and CLT did not differ significantly between bleeding and nonbleeding patients.Conclusions Rebalanced hemostatic status was confirmed in a large cohort of patients with acute liver injury/ALF, demonstrating that VWF/ADAMTS13 imbalance is associated with poor outcome and bleeding. The association between VWF/ADAMTS13 imbalance and bleeding suggests that bleeding in ALF relates more to systemic inflammation than a primary coagulopathy. |
Databáze: | OpenAIRE |
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