UNLABELLED: Emerging evidence supports the concept of a rebalanced hemostatic state in liver disease as a result of a commensurate decline in prohemostatic and antihemostatic drivers. In the present study, we assessed levels and functionality of the platelet-adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 in the plasma of patients with acute liver injury and acute liver failure (ALI/ALF). Furthermore, we explored possible associations between VWF, ADAMTS13, and disease outcome. We analyzed the plasma of 50 patients taken on the day of admission for ALI/ALF. The plasma of 40 healthy volunteers served as controls. VWF antigen levels were highly elevated in patients with ALI/ALF. In contrast, the collagen-binding activity and the ratio of the VWF ristocetin cofactor activity and VWF antigen was significantly decreased when compared with healthy controls. Also, the proportion of high molecular weight VWF multimers was reduced, despite severely decreased ADAMTS13 levels. In spite of these functional defects, platelet adhesion and aggregation were better supported by plasma of patients with ALI/ALF when compared with control plasma. Low ADAMTS13 activity, but not high VWF antigen, was associated with poor outcome in patients with ALI/ALF as evidenced by higher grades of encephalopathy, higher transplantation rates, and lower survival. VWF or ADAMTS13 levels were not associated with bleeding or thrombotic complications. CONCLUSION: Highly elevated levels of VWF in plasma of patients with ALI/ALF support platelet adhesion, despite a relative loss of function of the molecule. Furthermore, low ADAMTS13 activity is associated with progressive liver failure in the patient cohort, which might be attributed to platelet-induced microthrombus formation in the diseased liver resulting from a substantially unbalanced VWF/ADAMTS13 ratio.
UNLABELLED: Emerging evidence supports the concept of a rebalanced hemostatic state in liver disease as a result of a commensurate decline in prohemostatic and antihemostatic drivers. In the present study, we assessed levels and functionality of the platelet-adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 in the plasma of patients with acute liver injury and acute liver failure (ALI/ALF). Furthermore, we explored possible associations between VWF, ADAMTS13, and disease outcome. We analyzed the plasma of 50 patients taken on the day of admission for ALI/ALF. The plasma of 40 healthy volunteers served as controls. VWF antigen levels were highly elevated in patients with ALI/ALF. In contrast, the collagen-binding activity and the ratio of the VWF ristocetin cofactor activity and VWF antigen was significantly decreased when compared with healthy controls. Also, the proportion of high molecular weight VWF multimers was reduced, despite severely decreased ADAMTS13 levels. In spite of these functional defects, platelet adhesion and aggregation were better supported by plasma of patients with ALI/ALF when compared with control plasma. Low ADAMTS13 activity, but not high VWF antigen, was associated with poor outcome in patients with ALI/ALF as evidenced by higher grades of encephalopathy, higher transplantation rates, and lower survival. VWF or ADAMTS13 levels were not associated with bleeding or thrombotic complications. CONCLUSION: Highly elevated levels of VWF in plasma of patients with ALI/ALF support platelet adhesion, despite a relative loss of function of the molecule. Furthermore, low ADAMTS13 activity is associated with progressive liver failure in the patient cohort, which might be attributed to platelet-induced microthrombus formation in the diseased liver resulting from a substantially unbalanced VWF/ADAMTS13 ratio.
Authors: Kazuhisa Miyakawa; Nikita Joshi; Bradley P Sullivan; Ryan Albee; Christina Brandenberger; Hartmut Jaeschke; Mitchell R McGill; Michael A Scott; Patricia E Ganey; James P Luyendyk; Robert A Roth Journal: Blood Date: 2015-07-15 Impact factor: 22.113
Authors: Nikita Joshi; Anna K Kopec; Jessica L Ray; Holly Cline-Fedewa; Dafna J Groeneveld; Ton Lisman; James P Luyendyk Journal: Toxicol Appl Pharmacol Date: 2017-05-17 Impact factor: 4.219
Authors: David G Koch; J L Speiser; V Durkalski; R J Fontana; T Davern; B McGuire; R T Stravitz; A M Larson; I Liou; O Fix; M L Schilsky; T McCashland; J E Hay; N Murray; O S Shaikh; D Ganger; A Zaman; S B Han; R T Chung; R S Brown; S Munoz; K R Reddy; L Rossaro; R Satyanarayana; A J Hanje; J Olson; R M Subramanian; C Karvellas; B Hameed; A H Sherker; W M Lee; A Reuben Journal: Am J Gastroenterol Date: 2017-04-25 Impact factor: 10.864
Authors: Hai-Jian Sun; Jian Chen; Hao Zhang; Bing Ni; Jennifer C van Velkinburgh; Yao Liu; Yu-Zhang Wu; Xia Yang Journal: Immunol Res Date: 2017-10 Impact factor: 2.829