Kreutz Rolf P, Bitar Abbas, Owens Janelle, Desta Zeruesenay, Breall Jeffrey A, von der Lohe Elisabeth, Sinha Anjan, Vatta Matteo, Nystrom Perry, Jin Yan, Flockhart David A
Krannert Institute of Cardiology, Indiana University School of Medicine, 1800 N. Capitol Ave, ME-400, Indianapolis, IN, 46202, USA,
J Thromb Thrombolysis. 2014 Oct;38(3):380-7. doi: 10.1007/s11239-014-1059-4.
Factor XIII (FXIII) is necessary for cross linking of fibrin strands and generation of stable fibrin clot. FXIII Val34Leu is a common genetic single nucleotide polymorphism that has been associated with accelerated fibrin stabilization and reduced rate of fibrinolysis. The contribution of Val34Leu to long term risk of recurrent myocardial infarction (MI) in patients with coronary stenting has not been conclusively established. The objective of the study was to examine the effects of Val34Leu on fibrin generation, platelet aggregation, and long term clinical outcomes in patients with coronary artery disease treated with dual antiplatelet therapy. Patients with angiographically documented coronary artery disease who were treated with aspirin and clopidogrel were enrolled (n = 211). Light transmittance aggregometry and plasma fibrin clot formation using thrombelastography (TEG) were determined. Genotyping of Val34Leu was performed using Taqman assay. Clinical events during follow up were recorded. Homozygous carriers of 34 Leu variant had significantly shorter fibrin clot formation time as compared to wild type individuals (TEG K: 1.27 ± 0.3 vs. 1.68 ± 1.1 min, p = 0.011). The Val34Leu variant was associated with gene dose dependent increased risk of MI (log rank, p = 0.002) or occurrence of composite of MI and CV death (log rank, p = 0.005) with highest event rates observed in homozygous carriers of 34 Leu. In summary, FXIII Val34Leu polymorphism was associated with increased rate of fibrin stabilization in homozygous carriers of the variant and may increase risk of recurrent MI and death in patients with angiographically established coronary artery disease treated with dual antiplatelet therapy.
凝血因子 XIII（FXIII）对于纤维蛋白链的交联和稳定纤维蛋白凝块的形成是必需的。FXIII Val34Leu 是一种常见的基因单核苷酸多态性，与纤维蛋白稳定加速和纤维蛋白溶解速率降低有关。Val34Leu 对冠状动脉支架置入患者复发性心肌梗死（MI）的长期风险的影响尚未最终确定。本研究的目的是探讨 Val34Leu 对接受双联抗血小板治疗的冠心病患者纤维蛋白生成、血小板聚集和长期临床结局的影响。纳入经血管造影证实患有冠状动脉疾病且接受阿司匹林和氯吡格雷治疗的患者（n = 211）。采用透光率聚集法和血栓弹力图（TEG）测定血浆纤维蛋白凝块形成。使用 Taqman 分析法对 Val34Leu 进行基因分型。记录随访期间的临床事件。与野生型个体相比，34 Leu 变异体的纯合携带者的纤维蛋白凝块形成时间明显缩短（TEG K：1.27±0.3 分钟 vs. 1.68±1.1 分钟，p = 0.011）。Val34Leu 变异体与 MI 风险呈基因剂量依赖性增加（对数秩检验，p = 0.002）或 MI 与心血管死亡复合事件的发生率增加（对数秩检验，p = 0.005），在 34 Leu 的纯合携带者中观察到最高的事件发生率。总之，FXIII Val34Leu 多态性与变异体纯合携带者中纤维蛋白稳定速率增加有关，并且可能增加接受双联抗血小板治疗的经血管造影确诊的冠心病患者复发性 MI 和死亡的风险。
