Activated protein C resistence screening

Activated protein C resistance (APCR) is defined as a poor anticoagulant response of plasma to APC and has both hereditary and acquired causes. More than 95% of hereditary cases are due to the FV Leiden point mutation (changing arginine at 506 in FV gene to glutamine). This results in an impaired inactivation rate of FVa due to alteration of a protein C cleavage site. Native FVa is an important procoagulant co-factor to FXa in the prothrombinase complex and the result of the mutation is that thrombin formation will not be stopped as efficiently as in the case of inactivation of native FVa. Compared to normal FV genotype, the heterozygous defect is associated with 5 to 10 fold and homozygous defect with a 50 to 100 fold increased thrombosis risk. Other factor V mutations include FV Cambridge and FV Hong Kong. No mutations in the FVIII gene conferring APCR have been described. Acquired APCR has been described in pregnancy, patients with high FVIII levels, patients with anti-phospholipid antibodies, and is associated with use of the oral contraceptive pill.