Pseudohomozygosity for activated protein C resistance is a risk factor forvenous thrombosis

Pseudohomozygosity for activated protein C resistance (APC-r) is a rare con dition due to the association of heterozygous FV Leiden mutation and partia l type I FV deficiency. To assess the risk of venous thromboembolism in the se subjects, seven families including 11 pseudohomozygotes and 45 relatives were examined. Among the relatives, 16 were heterozygous FV Leiden carrier s, nine showed partial FV deficiency and 20 no abnormalities. Deep vein thr ombosis occurred in 4/11 (36.3%) pseudohomozygous patients versus 6/16 (37. 4%) FV Leiden carriers and 1/20 (5%) normal relatives. Pseudohomozygotes an d FV Leiden carriers had a significantly increased risk of venous thrombosi s in comparison to normal relatives (RR 8.8 and 5.7, respectively). There w as no difference between the thrombotic risk of pseudohomozygous subjects a nd of FV Leiden carriers (RR 1.6, 95% CI 0.43-5.7). Furthermore, there was no difference in thrombosis-free survival between pseudohomozygotes and 45 consecutive FV Leiden heterozygous outpatients, suggesting that a referral bias may explain the apparent younger age of thrombosis in the pseudohomozy gotes in comparison to relatives with FV Leiden heterozygosity (27 years v 54 years; P = 0.01). Pseudohomozygosity for APC resistance carries a signif icantly higher risk for venous thromboembolism in comparison to normal subj ects, but probably not in comparison to heterozygous FV Leiden carriers.