Rebalanced Hemostasis in Patients with Acute Liver Failure.

Patients with acute liver failure (ALF) have substantial alterations in their hemostatic system. Since an international normalized ratio of ≥ 1.5 is part of the definition of the syndrome, it has long been believed that patients with ALF had a hemostasis-related bleeding tendency. Recent data, however, show that spontaneous bleeding in ALF is rare. In addition, thrombotic complications may be more common than spontaneous bleeding complications. Laboratory studies have suggested that patients with ALF may be in hemostatic balance as a result of a commensurate decline in pro- and anti-hemostatic factors. The unstable nature of the hemostatic balance in ALF may explain the occurrence of both bleeding and thrombotic complications. The hemostatic profile of patients with ALF includes hypercoagulable features, including von Willebrand factor/a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 unbalance, elevated levels of highly procoagulant, platelet-derived microparticles, and a profound hypofibrinolytic status. These hypercoagulable features may contribute to systemic thrombotic complications, but may also drive intrahepatic clot formation. Studies in experimental animal models of ALF have demonstrated that intrahepatic clot formation contributes to disease progression. The clinical consequences of these new insights in the hemostatic system of patients with ALF will be discussed in this review. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.