Activated Protein C Resistance (APCR)


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Subject: Activated Protein C Resistance (APCR)

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  • APCR reflects resistance to proteolysis of activated factor V by activated protein C (APC). Ninety-five percent of APCR cases are due to factor V Leiden, a genetic mutation in factor V that predisposes to venous thromboembolism (5–10 times greater risk in heterozygotes and 50–100 times greater risk in homozygote carriers). The remaining 5% are found in pregnancy, malignancy, and the antiphospholipid antibody syndrome. Ratios are generated either from a modified PTT or, more recently, by activating protein C with southern copperhead venom, using dilute Russell viper venom as the clotting reagent. The test is performed in the presence of added APC, where in normal individuals, there is an elongation due to delayed generation of fibrin when factor V is lysed; in the absence of APC, where factor V remains intact, there is no elongation. Patients with APCR have a lesser prolongation of clotting in the presence of APC than controls.

  • Normal value: >1.8.


  • APCR is one of the assays recommended to investigate the etiology of venous thrombophilia. The congenital form, factor V Leiden, is present in 5% of individuals of European descent and in a high proportion of patients with unprovoked venous thromboembolism. It is virtually absent in patients of pure African ancestry.


  • Protein C levels <50% and initial anticoagulation with vitamin K antagonists may give falsely low ratios. In these situations, the genetic test for factor V Leiden is recommended. The APCR assay is valid in patients stabilized on vitamin K antagonists or heparin.

  • The assay is invalid in clotted specimens, as well as in lipemic, hemolyzed, or icteric samples. The assay is also invalid if blood is drawn with the wrong anticoagulant or the tubes are not filled appropriately.