High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin
High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin
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DOI：
10.1160/th08-06-0364
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发表时间：
2009-01-01
影响因子：
6.7
通讯作者：
van der Meer, Jan
中科院分区：
文献类型：
--
作者：
Brouwer, Jan-Leendert P.;Lijfering, Willem M.;van der Meer, Jan
蛋白S、蛋白C和抗凝血酶的遗传缺陷是首次静脉血栓栓塞的已知危险因素。我们评估了复发的绝对风险，并在一个大的队列中，这些缺陷的家庭伴随血栓性缺陷的贡献。在130例缺乏症患者中估计了年复发率，分别估计了蛋白S、蛋白C和抗凝血酶缺乏症患者和8例既往有静脉血栓栓塞症的非缺乏症患者。所有患者还检测了凝血因子V Leiden、凝血酶原G20210 A、高水平的凝血因子VIII、IX和XI以及高同型半胱氨酸血症。在130例缺陷患者中有81例复发事件。中位随访时间为4.6年。蛋白S缺乏症、蛋白C缺乏症、抗凝血酶缺乏症的复发性静脉血栓栓塞年发生率（95%置信区间）分别为8.4%（5.8-11.7）、6.0%（3.9-8.7）、10.0%（6.1-15.4），总体为7.7%（6.1-9.5）。自发性与激发性首次事件患者复发的相对风险为1.5（0.95-2.3）。1、5、10年的累积复发率分别为15%、38%和53%。伴随缺陷的复发相对风险为1.4（0.7-2.6）（1个缺陷）和1.4（0.8-2.7）（>= 2个缺陷）。8例非缺陷型患者的年发病率为1.0%（0.03-5.5）。口服抗凝剂治疗的缺乏患者的大出血年发生率为0.5%（0.2-1.0）。我们的结论是，遗传性蛋白S，蛋白C或抗凝血酶缺乏症的患者出现复发的绝对风险很高。这种风险在首次自发事件后增加，并伴随其他血栓性缺陷。
Hereditary deficiencies of protein S, protein C and antithrombin are known risk factors for first venous thromboembolism. We assessed the absolute risk of recurrence, and the contribution of concomitant thrombophilic defects in a large cohort of families with these deficiencies. Annual incidence of recurrence was estimated in 130 deficient patients, with separate estimates for those with each of protein S, protein C, and antithrombin deficiency, and in eight non-deficient patients with prior venous thromboembolism. All patients were also tested for factor V Leiden, prothrombin G20210A, high levels of factors VIII, IX and XI, and hyperhomocysteinemia. There were 81 recurrent events among 130 deficient patients. Median follow-up was 4.6 years. Annual incidences (95% confidence interval) of recurrent venous thromboembolism were 8.4% (5.8-11.7) for protein S deficiency, 6.0% (3.9-8.7) for protein C deficiency, 10.0% (6.1-15.4) for antithrombin deficiency, and overall 7.7% (6.1-9.5). Relative risk of recurrence in patients with a spontaneous versus provoked first event was 1.5 (0.95-2.3). Cumulative recurrence rates at 1, 5 and 10 years were 15%,38% and 53%. Relative risk of recurrence with concomitant defects was 1.4 (0.7-2.6) (1 defect) and 1.4 (0.8-2.7) (>= 2 defects). Annual incidence was 1.0% (0.03-5.5) in eight non-deficient patients. Annual incidence of major bleeding in deficient patients on oral anticoagulant treatment was 0.5% (0.2-1.0). We conclude that patients with a hereditary protein S, protein C or antithrombin deficiency appear to have a high absolute risk of recurrence. This risk is increased after a first spontaneous event, and by concomitance of other thrombophilic defects.