Abnormalities in blood coagulation, fibrinolysis, and platelet activation in adult patients after the Fontan procedure
Abnormalities in blood coagulation, fibrinolysis, and platelet activation in adult patients after the Fontan procedure
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DOI：
10.1016/j.jtcvs.2013.06.011
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发表时间：
2014-04-01
影响因子：
6
通讯作者：
Undas, Anetta
中科院分区：
文献类型：
--
作者：
Tomkiewicz-Pajak, Lidia;Hoffman, Piotr;Undas, Anetta
背景：Fontan手术后，高达30%的各种形式的先天性单心室患者会发生血栓形成。我们调查了成年Fontan患者的止血异常。方法：48例Fontan患者年龄在18-40岁之间，其中包括10例(21%)术后5-15年有血栓栓塞史的患者，以及年龄和性别匹配的35名对照组。结果：与正常对照组比较，方坦患者血浆凝血因子、凝血因子抑制物、纤溶标志物、血小板和内皮细胞活化指标降低，抗凝血酶和游离组织因子途径抑制物水平升高，但各项凝血因子和抑制物水平基本在正常范围内。Fontan患者凝血酶原片段1.2反映的凝血酶生成和血小板活化标志物增加。Fontan患者的血浆凝块溶解时间延长，这与凝血酶激活的纤溶抑制物活性增加有关。既往血栓栓塞者血氧饱和度、凝血因子V、VIII值、游离蛋白S降低，vonWillebrand因子、可溶性CD40L、P-选择素升高。其他实验室或临床指标与既往血栓形成无关。结论：成人Fontan患者的特点是血小板活化和内皮损伤增强，凝血酶形成增加，纤溶功能受损。Fontan手术后晚期观察到血栓栓塞症事件后，患者表现出游离蛋白S水平降低、血小板活化增加和内皮损伤。我们的发现提示了成人Fontan患者血栓前的新机制，这可能有助于优化血栓预防。
Background: Thrombosis occurs in up to 30% of patients with various forms of congenital single ventricle after the Fontan procedure. We investigated hemostatic abnormalities in adult Fontan patients.Methods: Forty-eight Fontan patients between ages 18 and 40 years, including 10 (21%) patients with previous thromboembolism 5 to 15 years after surgery, and 35 control subjects matched for age and sex were studied. Coagulation factors and inhibitors, together with markers of fibrinolysis, platelets, and endothelial activation, were determined in peripheral venous blood plasma.Results: Compared with control subjects, Fontan patients showed lower, although mostly within normal ranges, values of all coagulation factors, as well as reduced free protein S, in association with higher antithrombin and free tissue factor pathway inhibitor levels. Thrombin generation, reflected by prothrombin fragment 1.2, and platelet activation markers were increased in Fontan patients. The plasma clot lysis time was prolonged in Fontan patients, which was associated with an increased activity of thrombin-activatable fibrinolysis inhibitor. Fontan patients with previous thromboembolism had lower oxygen saturation, coagulation factors V and VIII, and free protein S, and increased vonWillebrand factor, soluble CD40 ligand, and P-selectin. Other laboratory or clinical parameters were not associated with prior thrombotic episodes.Conclusions: Adult Fontan patients are characterized by enhanced platelet activation and endothelial injury, heightened thrombin formation, and impaired fibrinolysis. Patients showed reduced free protein S levels, increased platelet activation, and endothelial damage after thromboembolic events observed late after Fontan surgery. Our findings indicate novel prothrombotic mechanisms in adult Fontan patients, which might help to optimize thromboprophylaxis.