Meltzer Mirjam E, Lisman Ton, Doggen Carine J M, de Groot Philip G, Rosendaal Frits R
Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS Med. 2008 May 6;5(5):e97. doi: 10.1371/journal.pmed.0050097.
Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.
Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors. Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.
The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.
此前，我们证实低纤溶活性（通过整体血凝块溶解试验测得的溶解血凝块能力降低）会增加静脉血栓形成的风险。在此，我们研究了低纤溶活性与已知的高凝相关危险因素的联合作用。
在静脉血栓形成危险因素的多环境与遗传评估（MEGA）研究中，采用基于血浆的血凝块溶解试验，对2090例静脉血栓形成患者和2564例年龄在18至70岁之间的对照参与者进行纤溶潜力测定，该研究是一项基于人群的静脉血栓形成病例对照研究。参与者完成了一份关于获得性危险因素的标准化问卷。仅低纤溶活性，即处于第四四分位数（最长凝块溶解时间）的凝块溶解时间（CLT）（在不存在其他相关危险因素的情况下）相对于处于第一四分位数（最短CLT）的个体，血栓形成风险增加约2倍。第一四分位数CLT的女性使用口服避孕药的比值比（OR）为2.6（95%置信区间[CI]1.6至4.0），而低纤溶活性且使用口服避孕药的女性静脉血栓形成风险增加超过20倍（OR 21.8，95%CI 10.2至46.7）。仅制动的OR为4.3（95%CI 3.2至5.8），制动合并低纤溶活性使风险增加10.3倍（95%CI 7.7至13.8）。仅因子V莱顿突变使风险增加3.5倍（95%CI 2.3至5.5），因子V莱顿突变携带者合并低纤溶活性的OR为8.1（95%CI 5.3至12.3）。低纤溶活性与凝血酶原20210A突变的联合并未协同增加风险。所有呈现的OR和95%CI均相对于第一四分位数CLT且无其他相关危险因素的个体。
低纤溶活性与口服避孕药使用、制动或因子V莱顿突变相结合导致的静脉血栓形成风险超过个体风险之和。
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