Rosendaal F R, Koster T, Vandenbroucke J P, Reitsma P H
Hemostasis and Thrombosis Research Center, Leiden, The Netherlands.
Blood. 1995 Mar 15;85(6):1504-8.
Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime.
对活化蛋白C（APC）抵抗是静脉血栓形成常见的遗传性危险因素，其与凝血因子V（因子V莱顿）突变有关。我们调查了这种异常纯合个体发生静脉血栓形成的风险。我们对471例年龄小于70岁首次客观确诊为深静脉血栓形成的连续患者以及474名健康对照者进行了因子V莱顿基因型测定。在血栓形成患者中我们发现85例杂合子和7例纯合子个体，在对照者中发现14例杂合子个体。根据哈迪-温伯格平衡计算得出对照者中纯合子个体的预期数量，估计为0.107（等位基因频率为1.5%）。杂合子个体的相对风险增加了7倍，而纯合子个体的相对风险增加了80倍。这些患者发生血栓形成的年龄要小得多（31岁对44岁）。纯合子个体以女性为主，很可能是口服避孕药的作用所致。由于血栓形成风险随年龄增加，无论是杂合子还是纯合子个体，绝对风险在老年患者中最为明显。对于纯合子个体，绝对风险可能达到每年几个百分点。这意味着大多数因子V莱顿纯合个体一生中至少会经历一次血栓形成事件。
