Diagnosis: Activated protein C resistance
• The first-generation functional assay for activated protein C resistance (APCR) was an activated partial thromboplastin time (aPTT) performed with and without the addition of activated protein C (APC). The APCR ratio was calculated as aPTT/aPTT with APC. An APCR ratio of less than 2.0 indicates an individual screening positive for APCR.
• First-generation assays were subject to false-negative and false-positive results because of factor deficiencies, the presence of heparin, warfarin therapy, and lupus anticoagulants (LACs).
• Second-generation, modified functional APCR assays are performed after diluting the sample with factor V–deficient plasma to replace any factor deficiencies, thus removing the effect of warfarin therapy or protein C deficiency. The assay also adds polybrene to neutralize unfractionated and low-molecular-weight heparin.
• Factor V–deficient plasma could have low protein S activity because of the manufacturing process. Therefore, protein S deficiency can still produce false-positive results.
• LACs are still problematic in second-generation assays, although dilution with factor V–deficient plasma dilutes the antibody and its effect.
• APCR assays are 100% sensitive for detecting factor V Leiden.
