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2194 Part XII: Hemostasis and Thrombosis Chapter 128: Hemostatic Alterations in Liver Disease and Liver Transplantation 2195

only reflect a reduced bleeding risk, but may even lead to a prothrom- in liver transplant recipients as a result of the perceived bleeding risk.
botic state. Studies indicate that deep vein thrombosis and pulmonary However, thrombotic complications do occur, and liver-related throm-
99
embolism can occur in patients with cirrhosis. 48,100 A large nation- bosis in particular, such as HAT and PVT, are of concern as they often
wide population-based case-control study in Denmark indicated that lead to graft loss. A single, uncontrolled retrospective study showed
patients with liver disease have a substantially increased risk for venous aspirin to substantially reduce the risk of posttransplantation HAT,
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thromboembolism compared to controls with an odds ratio of 1.7 for without increase of bleeding. Pulmonary emboli and intracardiac
patients with cirrhosis, and an odds ratio of 1.9 for patients with other thrombosis may occur during liver transplantation, indicating that the
48
liver diseases. Between 0.5 and 1.8 percent of all hospitalized patients hemostatic system may also tip toward thrombus formation during this
119
with cirrhosis developed venous thrombosis. Therefore liver disease procedure. Whether or not other anticoagulants will prevent postop-
should not be considered a contraindication for thromboprophylaxis erative thrombosis remains to be established.
with low-molecular-weight heparin (LMWH). Thromboprophylaxis is
warranted in patients that are immobilized or undergo surgery and in Role of Coagulation in Fibrosis of the Liver
hospitalized patients with active cancer. Treatment of venous thrombo- Thrombin, the key mediator of coagulation, also has several cellular
embolism in patients with liver disease is difficult, because of a higher effects mediated by protease-activated receptors (PARs). These PARs are
risk of bleeding associated with anticoagulant treatment than in healthy expressed on hepatic stellate cells (HSCs), which are mediators of liver
individuals, although recent data suggest that therapeutic dose LMWH fibrosis. Thrombin generation leads to activation of HSCs and fibrogen-
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is safe. 101–104 This, again, indicates that the balanced hemostatic system esis. Indeed, patients with prothrombotic phenotypes, such as carriers
in patients with cirrhosis involves a narrow safety margin. Furthermore, of the factor V Leiden mutation of antithrombin-deficient individuals
the choice of anticoagulant may be difficult. LMWH or unfractionated were shown to have enhanced progression of liver fibrosis in viral hep-
heparin may be difficult to monitor as a result of low levels of antith- atitis. 121,122 In line with these observations, fibrogenesis may be reduced
rombin. Anti–factor Xa measurement seems to be unreliable in patients by using anticoagulant treatment, however this has to be established in
with liver disease because of analytical problems. 102,105 Also monitoring clinical studies. 44
of treatment with vitamin K antagonists is difficult and may not be reli-
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44
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