Diagnostic approach to hypercoagulable states

The primary hypercoagulable states are inherited thrombotic disorders, resulting from mutations in genes encoding a plasma protein component of one of the coagulation mechanisms. The anticoagulant pathways most frequently involved include antithrombin III, protein C, and protein S deficiencies and activated protein C (APC) resistance. Around 80 % of all individuals with APC resistance carry a mutation of the factor V gene. Abnormalities in procoagulant pathways mostly concern elevated levels and/or function of procoagulant factors. Elevation in plasma prothrombin (FII) levels is associated with a FII gene mutation. Hyperhomocysteinemia as a risk factor for thrombosis is determined by genetic or dietary factors. The acquired or secondary hypercoagulable states consist of a heterogeneous group of disorders with an increased risk for developing thrombosis. Many underlying conditions (e.g., malignancies) may induce changes in the coagulation system. The risk of thrombosis is increased in individuals with antiphospholipid antibodies. They are found in about one-half of patients with systemic lupus erythematosus, but also in the course of infections, neoplastic diseases, and sometimes in apparently normal subjects. A definite molecular abnormality of hypercoagulable states can be identified in the special coagulation laboratory, using two types of molecular risk factors for thrombosis (genetic factors and abnormal laboratory phenotypes). Its recognition is useful for a prevention and/or therapy of thrombosis (Tab. 4, Ref. 10).