Resistance to activated protein C: a major cause of inherited thrombophilia.

Blood coagulation proteins play a major role in the development of pathological venous and arterial thrombosis. Inherited disorders of thrombosis are due to deficiencies of the anticoagulant proteins antithrombin, protein C, and protein S in 10% to 15% of individuals that present with venous thrombosis. A recently described cause of venous thrombosis is characterized by a poor response to activated protein C. In 90% of cases the activated protein C resistance is attributable to a mutation in the factor V gene (factor V Leiden). Activated protein C resistance is found in up to 7% of the Caucasian population but essentially unseen in other races. Activated protein C resistance is associated with a 5 to 10X increased risk of venous thrombosis in individuals that are heterozygous for the defect and a 50 to 100X increased risk in those individuals that are homozygous for factor V Leiden. Activated protein C resistance can be detected in the laboratory by modifications of the activated partial thromboplastin time assay. This assay is easy to perform and can be automated for a variety of instruments. Confirmation of the mutation of the factor V gene is accomplished through polymerase chain reactions that require DNA extraction from the patient's blood sample. Global assays that reflect the functionality of the protein C pathway have recently been introduced to the marketplace.