Anetta Undas, MD, PhD, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St., 31-202 Krakow, Poland, Tel.: +48 12 6143004, Fax: +48 12 6142120, E-mail:
Thromb Haemost. 2017 Aug 30;117(9):1739-1749. doi: 10.1160/TH17-01-0060. Epub 2017 Aug 3.
We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (K) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2-6 hours (h) after and 20-25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (K -12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for K and CLT before rivaroxaban intake. At 2-6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (K +38 %, and +37 %, CLT -25 % and -25 %, CLT-TAFI -20 % and -24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (K -12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20-25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.
我们旨在探究凝血酶原 G20210A 突变是否会改变静脉血栓栓塞症（VTE）后患者的血浆纤维蛋白凝块特性，以及利伐沙班的治疗如何影响这些改变。我们研究了 34 名凝血酶原突变杂合子携带者和性别及年龄匹配的 34 名非携带者，所有患者均在首次 VTE 发作后至少 3 个月，在接受利伐沙班（每天 20mg）治疗之前和治疗期间进行了研究。在基线、服用利伐沙班 2-6 小时（h）后和 20-25 h 后，评估了纤维蛋白溶解酶激活物抑制剂（TAFI）存在或不存在时的纤维蛋白凝块通透性（K）和纤维蛋白凝块溶解时间（CLT）。在基线时，与无突变组相比，凝血酶原突变组形成的凝块更致密（K-12%，p=0.0006），纤维蛋白溶解受损（CLT+14%，p=0.004 和 CLT-TAFI+13%，p=0.03），与 15 名无关的健康凝血酶原突变携带者相似。G20210A 凝血酶原突变是利伐沙班摄入前 K 和 CLT 的独立预测因子。在利伐沙班摄入 2-6 h 后，G20210A 携带者和非携带者的凝块特性均得到改善（K+38%和+37%，CLT-25%和-25%，CLT-TAFI-20%和-24%，均 p<0.001），但突变组的这些参数更差（K-12.8%，CLT+17%，CLT-TAFI+13%，均 p<0.001）。利伐沙班浓度与纤维蛋白凝块特性相关。在利伐沙班摄入后 20-25 h，大多数凝块特性恢复到基线。扫描电子显微镜图像证实了利伐沙班相关的凝块结构差异。总之，尽管利伐沙班治疗可改善纤维蛋白凝块特性，但无法消除 VTE 后凝血酶原突变携带者中观察到的更促血栓形成的纤维蛋白凝块表型。
