Activated Protein C Resistance Ratio (APCR)
Activated Protein C (APC) functions to cleave Factors V and VIII, reducing their ability to act as accelerators of thrombin generation.
Under some circumstances, FV and FVIII may be relatively resistant to cleavage by APC. This can lead to relatively uncontrolled thrombin production and a hypercoagulable state. The most common cause of APC Resistance is the presence of the Factor V Leiden mutation in which an amino acid at one of the three APC cleavage sites on FV has been replaced by another amino acid. Thus, APC does not recognize its principal cleavage site on the FV molecule, leading to enhanced thrombin production.
In the APCR test, the patient's plasma is first diluted in FV-deficient plasma. An APTT test is performed on the diluted plasma, with and without addition of purified APC. Normally, APC degrades the FV in the test sample (which should all come from the patient) and therefore prolongs the APTT. The result reported is a ratio - the clot time with APC divided by the clot time without APC. Normally, the addition of APC more than doubles the clot time - a normal APCR Ratio is therefore >2.0.
Most patients with a low (<2.0) APCR ratio performed in this way will carry the FV Leiden mutation. However, some patients with very strong Lupus Anticoagulants may give decreased values. We recommend that all patients with decreased APCR ratios are tested with a specific genetic test for FV Leiden.
If blood cells from the patient are available, the Hemostasis and Thrombosis Laboratory will reflexively test samples with a low APCR ratio (<2.0) with a specific DNA Microarray Signal Amplication Assay for the FV Leiden mutation
Heterozygotes for FV Leiden typically have APCR ratios in the range 1.5 - 2.0. Homozygotes usually have APRC ratios <1.5.