Chapter 8-7: Liver Disease–Induced Coagulopathy

TEXTBOOK PRESENTATION

The classic presentation of liver disease–induced coagulopathy is variable. Patients may be asymptomatic, only discovered to have a coagulopathy incidentally on coagulation laboratory studies. Spontaneous bleeding is uncommon, but anything that stresses the patient (such as an injury, an operative procedure, or perhaps NSAID-induced gastritis) may lead to more bleeding than one might normally anticipate with that event in someone without liver disease.

DISEASE HIGHLIGHTS

1. Patients with liver disease–induced coagulopathy typically have a disproportionately longer PT (and therefore higher INR) than aPTT.

2. The coagulopathy is caused by impaired production of clotting factors by the diseased liver; the clotting factor with the shortest half-life, namely factor VII, would be expected to be most prominently affected. Since the PT/INR is so sensitive to factor VII levels, that test is more notably abnormal.

3. Coagulopathy is seen primarily in patients with severe liver disease. The liver has a considerable reserve, and only when the impairment is severe does one find significant coagulopathy.

EVIDENCE-BASED DIAGNOSIS

1. In a patient with liver disease who is bleeding or in whom an invasive procedure is planned, the PT/INR and aPTT should be checked in order to screen for coagulation factor deficiencies.

   1. If the screening tests are significantly prolonged, one should check the levels of factor VII, factor V, factor II, factor IX, and factor X as well as fibrinogen to help determine which replacement therapy is most appropriate.

   2. If factor VII is low but factor V normal, it suggests that vitamin K deficiency may be playing a role (especially if history notes poor appetite for several weeks, suggesting an inadequate intake of vitamin K during that time), whereas in severe liver impairment, both factors V and VII are reduced.

   3. Because all the clotting factors except factor VIII are produced in the hepatocytes, all of them except factor VIII may be low in severe liver disease. Factor VIII is typically normal or even elevated in liver disease, a finding that may distinguish liver disease from DIC, in which factor VIII is low.

2. Another finding that may contribute to bleeding risk in severe liver disease is excessive fibrinolysis, the cause of which is a complex interplay between the production of and hepatic clearance of fibrinolytic activators and inhibitors.

3. While it may seem paradoxical, there may also be an increased risk of thrombosis in liver disease. Several findings may account for this: reduction of the vitamin K–dependent anticoagulant proteins, protein C and protein S; and increases in factor VIII and sometimes von Willebrand factor.

TREATMENT

1. Correct the coagulopathy using fresh frozen plasma to replete clotting factors. If the plasma fibrinogen level is particularly low (eg, < 100 mg/dL), infusion of cryoprecipitate may be helpful.

2. In severe cases, administration of recombinant activated factor VIIa may help stop the bleeding associated with liver disease; it is extremely expensive, however, ...