Abstract Number: PB0772
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Acquired Hemorrhagic Coagulation Disorders
Background: Although patients with acute liver failure (ALF) were considered to have a bleeding tendency, they rare bleed and have in fact rebalanced hemostasis with hypercoagulable features. This includes an unbalance between Von Willebrand Factor (VWF) and ADAMTS13 and a hypofibrinolytic status. Rodent models have shown a link between VWF, hepatic platelet accumulation, and ALF-progression.
Aims: Evaluation of the hemostatic state of ALF patients in relation to bleeding and clinical outcome.
Methods: Patients with ALF (INR (international normalized ratio) ≥1.5) or acute liver injury (ALI; INR ≥ 2.0) were recruited from the US ALF Study Group Registry between 2011 and 2018. Citrated plasma samples were taken on admission and VWF-levels, ADAMTS13-activity, thrombomodulin-modified thrombin generation, and clot lysis time (CLT) were determined, and compared to 40 healthy controls.
Results: We studied 676 patients, of whom 308 patients (45.6%) had acetaminophen-induced ALF. Bleeding occurred in 50 patients (7.4%), and 483 patients (71.4%) survived without liver transplantation. ALF patients had 5-fold increased VWF-levels, 5-fold decreased ADAMTS13-activity, similar thrombin generation, and 2.4-fold increased CLT, compared to controls. Patients with bleeding complications had higher VWF-levels (523% vs. 441%; p=0.0122), and lower ADAMTS13-activity (15% vs. 22%; p=0.005) compared to patients without bleeding. Thrombin generation and CLT did not differ significantly between bleeding and non-bleeding patients. Non-transplant-free survivors had higher VWF-levels (559% vs. 404%; p< 0.0001), lower ADAMTS13-activity (18% vs. 22%; p=0.0111), similar total thrombin generation, and shorter CLT (136 min vs. 146 min; p=0.04), compared to transplant-free survivors.
Conclusions: Hemostasis in a large cohort of ALF patients is characterized by VWF/ADAMTS13 unbalance, normocoagulability, and hypofibrinolysis, features which do not suggest a bleeding diathesis. The VWF/ADAMTS13 unbalance is associated with poor outcome, consistent with studies suggesting a detrimental effect of VWF in ALF in mice. The association between VWF/ADAMTS13 unbalance and bleeding complications suggests systemic inflammation rather than coagulopathy in ALF patients.
To cite this abstract in AMA style:
Driever E, Stravitz RT, Zhang J, Adelmeijer J, Durkalski V, Lee WM, Lisman T. The VWF/ADAMTS13 Unbalance, but Not Global Coagulation or Fibrinolytic Status, Is Associated with Outcome and Bleeding in Patients with Acute Liver Failure [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-vwf-adamts13-unbalance-but-not-global-coagulation-or-fibrinolytic-status-is-associated-with-outcome-and-bleeding-in-patients-with-acute-liver-failure/. Accessed September 22, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-vwf-adamts13-unbalance-but-not-global-coagulation-or-fibrinolytic-status-is-associated-with-outcome-and-bleeding-in-patients-with-acute-liver-failure/