Pseudo-Homozygous APC Resistance Due to Coinheritance of Heterozygous Factor V — R506Q and Type I Deficiency Associated with Thrombosis

Abstract

Resistance to activated protein C (APC resistance) is the most frequent inherited hypercoagulable state that represents a common risk factor for venous thrombosis [1]. This resistance is due to a G > A substitution in position 1691 of factor V (FV) gene which leads to the synthesis of an abnormal FV molecule (FV Leiden) where Arg 506, the first cleavage site of APC is replaced by Gln [2]. As a consequence FV Leiden heterozygotes experience a seven-fold increased risk of venous thromboembolism and homozygotes an 80-fold increased risk when compared with non-carrier [3]. Although there is a good correlation between the APC-ratio laboratory test and genotype for the Leiden mutation, a number of genotype/phenotype discrepancies have been observed. Among these is the so called pseudo-homozygous APC resistance. This condition is characterized by co-inheritance of the FV Leiden and FV null mutation on different alleles [4, 5]. Although partial FV deficiency could compensate for the thombotic defect, all of the very few cases reported so far are thrombophilic patients. Here we report a case of pseudo-homozygous FV Leiden associated with FV deficiency due to a null mutation in the FV gene.