THE FACTOR V LEIDEN (R506Q) MUTATION AND RISK OF THROMBOSIS IN RENAL TRANSPLANT RECIPIENTS1

Abstract

BACKGROUND: Renal transplantation and chronic renal failure are associated with an increased risk of venous thrombosis and myocardial infarction (MI). We investigated whether resistance to activated protein C due to a mutation in the factor V gene (FV Leiden/FV506Q) may predispose patients to thrombosis. METHODS: Three hundred patients who had undergone renal transplantation were genotyped for the FV mutation. Seventy-seven patients who had suffered thrombotic complications (42 venous, 28 arterial, and 7 both) were compared with 223 patients free of thrombosis. RESULTS: Thirty-two patients had suffered early renal allograft thrombosis (30 venous), and 33 patients had suffered MI. A higher proportion of the patients with thrombosis, compared to those without, had a family history of arterial cardiovascular disease (42% vs. 26%, P=0.04). Eighteen (6%) patients were heterozygous for FV506Q and seven (39%) of these had suffered venous thrombosis (including four primary allograft thromboses), compared with 15% of the patients without the mutation (P<0.05). The odds ratio for risk of venous thrombosis for FV506Q carriers was 3.6 (95% confidence interval: 1.3-9.9) or 4.0 (1.2-13.8) for primary allograft thrombosis. Only one of the FV506Q carriers had suffered an MI. CONCLUSIONS: Carriers of the factor V 506Q mutation with chronic renal failure who have undergone transplantation are at an increased risk of venous but not arterial thrombosis. This mutation explained 14% of all venous and 20% of primary allograft thrombosis, suggesting that other unidentified genetic and environmental factors contribute to the risk of thrombosis in renal transplant recipients.