Meinardi J R, Middeldorp S, de Kam P J, Koopman M M, van Pampus E C, Hamulyák K, Prins M H, Büller H R, van der Meer J
Division of Haemostasis, Thrombosis and Rheology, University Hospital, Groningen, The Netherlands.
Blood Coagul Fibrinolysis. 2001 Dec;12(8):713-20. doi: 10.1097/00001721-200112000-00014.
Factor V Leiden is the most common genetic defect associated with venous thromboembolism. Its clinical expression is limited and shows a wide intrafamilial and interfamilial variation, which might be explained by the influence of other genetic risk factors. We retrospectively studied 226 patients with factor V Leiden and documented venous thromboembolism (probands) and 400 first-degree carrier relatives to assess the contribution of concomitant genetic risk factors to the occurrence of venous thromboembolism. The prothrombin G20210A mutation was found in 8.3%, homozygosity of factor V Leiden in 7.2%, and inherited deficiencies of antithrombin, protein C or protein S in 4.7% of symptomatic carriers (probands and relatives), as compared with 6.0, 3.4 and 0.9% of asymptomatic carriers, respectively. The total follow-up time in relatives was 11 049 years. Prevalences of venous thromboembolism were 10.8% in single heterozygous factor V Leiden carrier relatives, 16.0% in double-heterozygotes for factor V Leiden and the prothrombin mutation, 36.8% in homozygotes for factor V Leiden, and 40.0% in double-heterozygotes for factor V Leiden and an inherited deficiency of protein C or protein S. Annual incidences in these groups were 0.39, 0.57, 1.41, and 4.76%, respectively. Multivariate analysis showed a small, non-significant additional effect of the prothrombin mutation on the risk of venous thromboembolism in heterozygotes for factor V Leiden [adjusted hazard ratio, 1.3; 95% confidence interval (CI), 0.5-3.8]. This effect was more pronounced for homozygosity of factor V Leiden (adjusted hazard ratio, 3.9; 95% CI, 1.7-9.0) and inherited protein C or protein S deficiencies (adjusted hazard ratio, 17.5; 95% CI, 3.8-81.2). Our data provide evidence of clustering of the evaluated genetic thrombophilic defects in symptomatic factor V Leiden carriers and support the assumption that the clinical expression of factor V Leiden depends on clustering in a part of carriers.
因子V莱顿突变是与静脉血栓栓塞相关的最常见遗传缺陷。其临床表现有限，且在家族内和家族间存在广泛差异，这可能是由其他遗传风险因素的影响所致。我们对226例携带因子V莱顿突变且有静脉血栓栓塞记录的患者（先证者）以及400名一级携带者亲属进行了回顾性研究，以评估伴随的遗传风险因素对静脉血栓栓塞发生的影响。在有症状的携带者（先证者和亲属）中，凝血酶原G20210A突变的检出率为8.3%，因子V莱顿纯合子为7.2%，抗凝血酶、蛋白C或蛋白S遗传性缺乏为4.7%；而在无症状携带者中，相应的检出率分别为6.0%、3.4%和0.9%。亲属的总随访时间为11049人年。因子V莱顿单杂合子携带者亲属的静脉血栓栓塞患病率为10.8%，因子V莱顿与凝血酶原突变的双杂合子为16.0%，因子V莱顿纯合子为36.8%，因子V莱顿与蛋白C或蛋白S遗传性缺乏的双杂合子为40.0%。这些组的年发病率分别为0.39%、0.57%、1.41%和4.76%。多变量分析显示，凝血酶原突变对因子V莱顿杂合子静脉血栓栓塞风险的额外影响较小且无统计学意义[校正风险比，1.3；95%置信区间（CI），0.5 - 3.8]。这种影响在因子V莱顿纯合子（校正风险比，3.9；95%CI，1.7 - 9.0）和蛋白C或蛋白S遗传性缺乏（校正风险比，17.5；95%CI，3.8 - 81.2）中更为明显。我们的数据为有症状的因子V莱顿携带者中所评估的遗传性血栓形成缺陷的聚集提供了证据，并支持因子V莱顿的临床表型取决于部分携带者中缺陷聚集的假设。
