42), and was not correlated with MELD scores (r = 0.19, P = 0.21). Table 2 shows that other complications of ALI/ALF were not associated with admission ADAMTS13 activity or VWF:Ag levels in this cohort. Notably, ADAMTS13 activity or VWF antigen levels were not associated with bleeding or thrombosis. This study shows a remarkable elevation of VWF levels BKM120 concentration in plasma

of patients with ALI/ALF, comparable to the high VWF levels we reported in patients with chronic liver disease.[8] In addition, associated with these high levels of VWF, plasma from patients with ALI/ALF better supported platelet adhesion and aggregation under shear conditions compared with plasma from healthy individuals, consistent with prior observations in cirrhotic plasma.[8] The enhanced platelet adhesion and aggregation occur despite a loss of function of VWF in ALI/ALF as evidenced by a reduced VWF:RCo/VWF:Ag ratio and a reduced collagen-binding activity. Apparently, the decrease in function of VWF is more than compensated for by the quantitative increase in concentration

of the molecule. We are systematically studying consequences of hemostatic defects in patients with ALF. First, we have shown that parameters reflecting primary and secondary hemostasis were normal when assessed by thromboelastography.[7] Secondly, we demonstrated an intact capacity of the secondary hemostatic system to support thrombin generation despite abnormal laboratory test of coagulation such as the PT/INR.[5] The data presented in this study suggest Roxadustat chemical structure that the primary hemostatic system remains functional, perhaps even overcompensated, as the net effect of alterations in components of the system. Fludarabine mw We believe that the message of our combined investigations suggests that the hemostatic system of patients with ALF is in fact rebalanced with a normal function, similar to the hemostatic rebalance observed in patients with cirrhosis.[1] This observation may have important clinical consequences. The presence of physiological compensatory

mechanisms, such as high VWF levels, sustaining appropriate hemostasis, suggests that the routine correction of abnormal tests of hemostatic function may be unnecessary in patients with ALI/ALF. Indeed, prohemostatic replacement therapy is often initiated based on the assumption that a prolonged PT/INR, but also a decreased platelet count and function, indicates a bleeding risk.[23] Our data suggest that the prophylactic administration of platelet concentrates in ALI/ALF patients with thrombocytopenia or platelet function defects may not be indicated, and may even result in an increased risk of thrombotic complications. In addition to high VWF levels, we also observed a severe decrease of levels of the VWF cleaving protease, ADAMTS13, in the present study.