Libourel Eduard J, Bank Ivan, Meinardi Johan R, Baljé -Volkers Corinne P, Hamulyak Karly, Middeldorp Saskia, Koopman Maria M W, van Pampus Elisabeth C M, Prins Martin H, Büller Harry R, van der Meer Jan
Division of Hemostasis, Thrombosis and Rheology, University Hospital Groningen, the Netherlands.
Haematologica. 2002 Oct;87(10):1068-73.
The clinical expression of factor V Leiden varies widely within and between families and only a minority of carriers will ever develop venous thromboembolism. Co-segregation of thrombophilic disorders is a possible explanation. Our aim was to assess the contributions of high levels of factor VIII:C, factor XI:C, thrombin activatable fibrinolysis inhibitor (TAFI) and lipoprotein (a) (Lp(a)) to the risk of venous thromboembolism in factor V Leiden carriers.
Levels of the four proteins were measured, in addition to tests of deficiencies for antithrombin, protein C and protein S, and the prothrombin G20210A mutation, in 153 factor V Leiden carriers, derived from a family cohort study. The (adjusted) relative risk and absolute risk of venous thromboembolism for high levels of each protein were calculated.
Of carriers, 60% had one or more concomitant thrombophilic disorders. Crude odds ratios (95% CI) of venous thromboembolism for high protein levels were: 3.2 (1.1-9.3) (factor VIII:C); 1.7 (0.6-4.9) (factor XI:C); 3.0 (1.1-8.2) (TAFI); and 1.9 (0.7-5.7) (Lp(a)). Adjusted for age, sex, other concomitant thrombophilic disorders and exogenous risk factors, the odds ratio for venous thromboembolism were 2.7 (0.8-8.7) for high factor VIII:C levels and 1.8 (0.6-5.3) for high TAFI levels. Annual incidences in subgroups of carriers were 0.35% (0.09-0.89), 0.44% (0.05-1.57) and 0.94% (0.35-2.05) for concomitance of high levels of factor VIII:C, TAFI and both, respectively, as compared to 0.09% (0.00-0.48) in single factor V Leiden carriers and 1.11% (0.30-2.82) for other concomitant disorders.
High levels of factor VIII:C and TAFI, in contrast with factor XI:C and Lp(a), are mild risk factors for venous thromboembolism, and substantially contribute to the risk of venous thromboembolism in factor V Leiden carriers. Our data support the hypothesis that the clinical expression of factor V Leiden depends on co-segregation of thrombophilic disorders.
因子V莱顿突变的临床表现在家族内部和家族之间差异很大，只有少数携带者会发生静脉血栓栓塞。血栓形成倾向疾病的共同遗传是一种可能的解释。我们的目的是评估高水平的因子VIII:C、因子XI:C、凝血酶激活的纤维蛋白溶解抑制剂（TAFI）和脂蛋白(a)（Lp(a)）对因子V莱顿突变携带者发生静脉血栓栓塞风险的影响。
在一项家族队列研究中选取了153名因子V莱顿突变携带者，除了检测抗凝血酶、蛋白C和蛋白S缺乏症以及凝血酶原G20210A突变外，还测量了这四种蛋白质的水平。计算了每种蛋白质高水平时静脉血栓栓塞的（调整后）相对风险和绝对风险。
在携带者中，60%患有一种或多种合并的血栓形成倾向疾病。高蛋白水平时静脉血栓栓塞的粗比值比（95%CI）分别为：3.2（1.1 - 9.3）（因子VIII:C）；1.7（0.6 - 4.9）（因子XI:C）；3.0（1.1 - 8.2）（TAFI）；1.9（0.7 - 5.7）（Lp(a)）。在调整年龄、性别、其他合并的血栓形成倾向疾病和外源性危险因素后，因子VIII:C高水平时静脉血栓栓塞的比值比为2.7（0.8 - 8.7），TAFI高水平时为1.8（0.6 - 5.3）。携带者亚组中，因子VIII:C、TAFI高水平以及两者均高水平时的年发病率分别为0.35%（0.09 - 0.89）、0.44%（0.05 - 1.57）和0.94%（0.35 - 2.05），而单纯因子V莱顿突变携带者的年发病率为0.09%（0.00 - 0.48），其他合并疾病者为1.11%（0.30 - 2.82）。
与因子XI:C和Lp(a)不同，高水平的因子VIII:C和TAFI是静脉血栓栓塞的轻度危险因素，并在很大程度上增加了因子V莱顿突变携带者发生静脉血栓栓塞的风险。我们的数据支持因子V莱顿突变的临床表型取决于血栓形成倾向疾病共同遗传的假说。
