Malyszko J, Malyszko J S, Hryszko T, Mysliwiec M
Department of Nephrology and Transplantology, Medical University, 15-540 Bialystok, Zurawia 14, Poland.
Transplant Proc. 2003 Dec;35(8):2940-2. doi: 10.1016/j.transproceed.2003.10.051.
Cyclosporine (CyA) has been implicated to increase cardiovascular morbidity and mortality after renal transplantation. Impairment of the fibrinolytic system is one factor involved in the development of thrombotic complications. The aim of this study was to compare hematological and hemostatic parameters among patients on CyA, azathioprine, and prednisone (n = 31) versus CyA and steroids (n = 14). Using commercially available kits we evaluated thrombin activity as thrombin-antithrombin complexes (TAT), prothrombin fragments (1 + 2), thrombin activatable fibrinolysis inhibitor-(TAFI), TAFI activator, thrombomodulin (TM)-a marker for endothelial cell injury,-plasmin generation (plasmin-antiplasmin complex PAP), a glycoprotein linking coagulation and fibrinolysis. We observed that patients not treated with azathioprine displayed longer prothrombin times and activated partial thromboplastin times; higher fibrinogen, platelet counts and fibrinolytic activity index (FAI); shorter euglobulin clot lysis time; as well as lower thrombin generation markers namely, prothrombin fragments 1 + 2 and thrombin-antithrombin complexes. Although patients in the non-AZA group tended to have been engrafted for a longer time (P =.086), the groups did not differ with regard to age, BMI, erythrocyte count, hematocrit, leukocyte count, creatinine clearance, alanine and asparagine aminotransferase activities mean arterial blood pressure, fibrinogen, TAFI, thrombomodulin, or plasmin-antiplasmin complexes. These findings suggest that kidney transplant recipients on triple therapy are at greater risk of cardiovascular disease than those without azathioprine treatment, despite the lower fibrinolytic activity.
环孢素(CyA)被认为会增加肾移植后心血管疾病的发病率和死亡率。纤维蛋白溶解系统受损是血栓形成并发症发生的一个因素。本研究的目的是比较接受环孢素、硫唑嘌呤和泼尼松治疗的患者(n = 31)与接受环孢素和类固醇治疗的患者(n = 14)之间的血液学和止血参数。我们使用市售试剂盒评估了凝血酶活性,以凝血酶 - 抗凝血酶复合物(TAT)、凝血酶原片段(1 + 2)、凝血酶激活的纤维蛋白溶解抑制剂 -(TAFI)、TAFI激活剂、血栓调节蛋白(TM)- 内皮细胞损伤标志物、纤溶酶生成(纤溶酶 - 抗纤溶酶复合物PAP),一种连接凝血和纤维蛋白溶解的糖蛋白。我们观察到未接受硫唑嘌呤治疗的患者凝血酶原时间和活化部分凝血活酶时间更长;纤维蛋白原、血小板计数和纤维蛋白溶解活性指数(FAI)更高;优球蛋白凝块溶解时间更短;以及凝血酶生成标志物即凝血酶原片段1 + 2和凝血酶 - 抗凝血酶复合物更低。尽管非硫唑嘌呤组的患者移植时间往往更长(P = 0.086),但两组在年龄、体重指数、红细胞计数、血细胞比容、白细胞计数、肌酐清除率、丙氨酸和天冬氨酸转氨酶活性、平均动脉血压、纤维蛋白原、TAFI、血栓调节蛋白或纤溶酶 - 抗纤溶酶复合物方面没有差异。这些发现表明,三联疗法的肾移植受者比未接受硫唑嘌呤治疗的患者患心血管疾病的风险更高,尽管纤维蛋白溶解活性较低。