Together, these findings may lead to novel therapies for liver injury. Additional Supporting Information may be found in the online version of this article. “
“Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011;365:147-156. (Reprinted with permission.) The reassessment of hemostasis in patients with chronic liver disease challenges the dogma that the
major coagulopathy in these patients leads consistently to bleeding. Other changes that accompany chronic liver disease may restore the balance of anticoagulant and procoagulant effects. In certain circumstances, the risk of thrombotic events may be greater than the risk of hemorrhage. We speculate that drugs that are often regarded as contraindicated in patients with chronic selleck antibody inhibitor liver disease may instead prove beneficial and should be tested in
appropriate clinical trials. For any provider who cares for patients with liver disease, whether directly or in a supportive or procedural capacity, bleeding from one site or another has likely left an indelible, and often dour, clinical impression. This feeling is especially amplified when the bleeding originates from one’s own puncture or biopsy site. The prothrombin time (PT) and international Selisistat clinical trial normalized ration (INR) are reliable measures of coagulation in warfarin-treated patients. It stands to good reason that direct extrapolation and application of PT/INR to cirrhosis patients should provide a practical measure of bleeding risk and serve as a reliable
guide for therapy and prevention of bleeding. However, for those who have practiced this concept for many years, the emergence of a contrary body of literature may be difficult to digest. Sorafenib purchase Nonetheless, it is currently evident that the hemostatic system in liver disease patients is far more complex than the PT/INR. Indeed, these patients may be relatively hypercoagulable, in spite of prolongation of the PT/INR. These paradoxical relationships have recently been summarized in an important article from two key investigators in this field, Armando Tripodi and Pier Mannuccio Mannucci. 1 Investigations over the recent past have redefined the “balance” of the coagulation cascade in cirrhosis patients as a more sensitive state of equilibrium, where perturbations can result in either a hypo- or hypercoagulation clinical event. From a simplified perspective (Fig. 1), coagulation in the cell-based model of hemostasis originates at a site of vascular breach from activation of tissue factor and factor VII on the phospholipid membrane of a platelet (or adventitial cell). This, in turn, leads to assembly of activated factors X and V (prothrombinase complex), which results in a “priming” amount of thrombin (factor II) and initiation of fibrin production from fibrinogen.