The patient most likely has liver failure resulting from excessive acetaminophen use as the cause of his coagulopathy. He takes chronic warfarin therapy but presents with a significant coagulopathy of unclear cause. Specific factor level measurement is useful when it is clinically helpful to understand the basis of a coagulation disorder to guide therapy. A panel of factors, including factor V, factor VII, and factor VIII, may be checked when it is important to distinguish between liver failure, disseminated intravascular coagulation, or vitamin K deficiency/warfarin overdose. In liver failure, all clotting factor activity levels are low except for factor VIII, which is synthesized in all endothelial cells rather than only hepatic endothelial cells. Additionally, good hepatic function is required for factor VIII clearance, thus factor VIII levels increase in liver disease. Patients with severe liver failure (and on occasion those with acute liver failure) will have prolonged prothrombin and activated partial thromboplastin times because of decreased levels of coagulation factors. This is called the coagulopathy of liver disease. The elevated D-dimer level is also consistent with liver disease, because D-dimers are cleared by the liver; a high D-dimer level does not automatically indicate disseminated intravascular coagulation (DIC).

DIC begins with abnormal thrombin generation, rapid consumption of clotting factors and platelets, and accelerated fibrinolysis. Although hemorrhage may result from low levels of clotting factors and platelets, histopathologic examination of affected tissues shows a fibrin clot in the microvasculature. A thrombotic microangiopathy may ensue, and schistocytes develop in 30% of patients. An elevated factor VIII level, as seen in this patient, rules out DIC.

Factor V levels can be used to distinguish between liver disease and vitamin K deficiency, because factor V is synthesized in the liver but is not a vitamin K–dependent factor. Thus, someone with vitamin K deficiency will have normal levels of factor V, whereas a patient with liver failure will have low factor V levels. This patient's low factor V level rules out warfarin overdose as well as vitamin K deficiency, because normal levels would be expected in vitamin K deficiency.