An assessment of the comparative utility of functional and molecular level analyses in the investigation of patients with thrombophilia.

Aim —To determine the relation of the low anticoagulant response phenotype with the Factor V Q506 (Leiden) mutation in a cohort of patients with thrombophilia. Methods —Fifty four patients with either a personal or family history of deep vein thrombosis were investigated both for their anticoagulant response by the activated protein C resistance test (APCR) and their genetic status in respect of the Leiden mutation by means of a PCR-RFLP method. Results —Low APCR ratios do not necessarily predict possession of the Leiden mutation. Conversely, normal ratios do not exclude the mutation. Of 14 individuals with low APCR ratios, the Leiden mutation was absent in five. Of the remainder, three were heterozygous and six homozygous. Of nine heterozygote individuals, only three had low APCR ratios. All patients homozygous for the defect had low APCR ratios. Conclusions —These results lend further weight to the hypothesis that the APC resistant phenotype results from more than one genetic defect and indicate the value of combined functional and molecular investigations in all patients with thrombophilia.