Heidenreich S, Dercken C, August C, Koch H G, Nowak-Göttl U
Department of Renal Medicine, University of Münster, Germany.
J Am Soc Nephrol. 1998 Jul;9(7):1309-13. doi: 10.1681/ASN.V971309.
Inherited and acquired thrombophilic disorders predispose patients for thromboembolic and probably other occlusive vascular events that occur when additional risk factors play in concert. Because acute rejections in renal transplant recipients may reflect vascular events, and an impairment of the fibrinolytic system in immunosuppressed patients has been previously described, the implications of genetic or acquired risk factors of thrombophilia for the occurrence of early acute rejections after kidney transplantation were evaluated. The following risk factors of thrombophilia were determined in 97 patients after cadaveric kidney transplantation: factor V Leiden mutation, protein S, protein C, and antithrombin deficiency. In a retrospective analysis, the prevalence of acute rejections, the histologic classification when rejection episodes had been confirmed by biopsy, and other vascular complications were evaluated. In 21 of the 97 patients, an inherited or acquired risk factor of thrombophilia was detected. Prevalence of acute rejections was 71% in the first 6 mo after transplantation in patients with a thrombophilic disorder and significantly higher compared with patients without thrombophilia (41%; P = 0.017). The distribution of classic risk factors associated with acute rejections, such as number of human leukocyte antigen mismatches or percentage of panel-reactive antibodies, was similar in patients with and without thrombophilia. In the eight patients with thrombophilia and histologically proven acute rejection, four patients had an acute vascular rejection, and in two patients a vascular involvement was suspected. Furthermore, prevalence of cerebral or coronary vascular disease, or venous thromboembolic complications, was significantly higher in patients with a thrombophilic clotting defect (67%) compared with patients with normal hemostasis parameters (28%; P < 0.002). It is concluded that renal allograft recipients with thrombophilia are at risk of developing an acute rejection or other vascular event. Although the determination of thrombotic risk factors was performed at least 3 mo after an acute rejection episode, it can be presumed that acute rejection episodes are associated with subsequent coagulatory abnormalities with further consequences for transplant survival. Thus, pretransplant evaluation of genetic and acquired risk factors of thrombophilia is recommended.
遗传性和获得性血栓形成倾向疾病使患者易发生血栓栓塞事件，并且在其他危险因素共同作用时可能发生其他闭塞性血管事件。由于肾移植受者的急性排斥反应可能反映血管事件，并且先前已描述免疫抑制患者的纤维蛋白溶解系统受损，因此评估了血栓形成倾向的遗传或获得性危险因素对肾移植后早期急性排斥反应发生的影响。对97例尸体肾移植后的患者确定了以下血栓形成倾向危险因素：凝血因子V莱顿突变、蛋白S、蛋白C和抗凝血酶缺乏。在一项回顾性分析中，评估了急性排斥反应的发生率、活检证实有排斥反应发作时的组织学分类以及其他血管并发症。在97例患者中的21例中，检测到遗传性或获得性血栓形成倾向危险因素。有血栓形成倾向疾病的患者在移植后的前6个月内急性排斥反应的发生率为71%，与无血栓形成倾向的患者相比显著更高（41%；P = 0.017）。有和无血栓形成倾向的患者中，与急性排斥反应相关的经典危险因素分布相似，如人类白细胞抗原错配数或群体反应性抗体百分比。在8例有血栓形成倾向且经组织学证实有急性排斥反应的患者中，4例发生急性血管排斥反应，2例疑似有血管受累。此外，有血栓形成倾向凝血缺陷的患者中，脑血管或冠状动脉疾病或静脉血栓栓塞并发症的发生率（67%）显著高于止血参数正常的患者（28%；P < 0.002）。得出的结论是，有血栓形成倾向的肾移植受者有发生急性排斥反应或其他血管事件的风险。尽管血栓形成危险因素的测定是在急性排斥反应发作至少3个月后进行的，但可以推测急性排斥反应发作与随后的凝血异常相关，对移植存活有进一步影响。因此，建议在移植前评估血栓形成倾向的遗传和获得性危险因素。
