Temporal changes in the activated protein C resistance ratio in a heterozygote for factor V Leiden are abolished by dilution in factor V-deficient plasma
Article
Meyer, T, Garcia, M, Helms, E, Francis, DA, Francis, JL
abstract
Activated protein C resistance (APCR) is the single most common cause of hereditary thrombophilia and is caused by a mutation in the factor V molecule (FV Leiden). Screening for this defect has become a standard part of the laboratory evaluation of thrombophilia. However, the original APTT-based screening test does not discriminate completely between normal individuals and heterozygotes for FV Leiden. Diluting the patient's plasma in factor V-deficient plasma greatly improves the predictive ability of this test for the FV Leiden mutation. In this report we show that a heterozygote for FV Leiden (confirmed by DNA analysis) showed marked temporal variation in APCR ratio when tested by the original coagulation-based technique. Specifically, this individual tested normal in five of seven occasions tested (APCR ratio range 1.98-2.53; normal >2.0). Using the modified method, although some temporal variation remained, the diagnosis of APCR would have been made on every occasion (APCR ratio 1.85-2.12; normal >2.3). These findings constitute a further reason to use the modified procedure for APCR screening.