Endogenous tPA is cleared by the liver and therefore circulating levels of tPA are elevated in patients with cirrhosis. This is the main reason that these patients bleed. Phrased another way, the main hemostatic defect in liver disease is not thrombin generation (defective production of procoagulant clotting factors) but rather accelerated clot lysis. Therefore, an antifibrinolytic treatment (like amiocaproic acid) that inhibits the binding of fibrinolytic molecules (plasmin, plasminogen) to fibrin and thus helps prevent breakdown of existing clots is an elegant and effective way to treat bleeding in cirrhosis. A reduced dose should be given in patients with renal dysfunction and it should be noted that this drug has been associated with AKI in some patients due to urinary tract obstruction and ATN.
Posted by Rebecca Karp Leaf MD and Walter Dzik MD.
Controversial. "Cirrhosis has been variably associated with laboratory changes favoring hyperfibrinolysis, such as increased levels of t-PA and reduced levels of plasmin inhibitor and TAFI, but also with changes favoring hypofibrinolysis, such as reduced levels of plasminogen and increased levels of PAI." In vitro assays of fibrinolytic components are likely to be misleading – as are standard coag tests are in defining the bleeding tendency of liver disease. All unsatisfactory; more work needed.
Ref: Tripodi and Mannucci 2011, The coagulopathy of liver disease (nice review) NEJM 365:147-56
some references would be nice. Thank you