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.
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D001778:Blood Coagulation Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D005821:Genetic Techniques; D006801:Humans; D010314:Partial Thromboplastin Time; D017354:Point Mutation; D011486:Protein C / Q000235:genetics / Q000378:metabolism*; D013924:Thrombophlebitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism