Friedman G S, Wik D, Silva L, Abdou J C, Meier-Kriesche H U, Kaplan B, Bonomini L, DeFranco P, Lyman N, Mulgaonkar S, Jacobs M
Saint Barnabas Medical Center, Department of Transplantation, Livingston, New Jersey 07039, USA.
Transplantation. 2000 May 27;69(10):2099-102. doi: 10.1097/00007890-200005270-00022.
Fabry's disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabry's disease prompted prospective evaluation of all transplant candidates with Fabry's disease for hypercoagulability.
Transplant candidates with Fabry's disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability.
A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(+) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38.
Due to the observed increase in the incidence of APCR in our Fabry's cohort, we suggest screening all patients with Fabry's disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabry's disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabry's disease may further elucidate HLA-based association of Fabry's disease and resistance to activated protein C with the risk of thrombosis and rejection.
法布里病与血栓形成事件及排斥反应的发生率增加相关。一名患有法布里病的受者体内功能正常的尸体肾移植发生自发性血栓形成，促使对所有患有法布里病的移植候选者进行高凝状态的前瞻性评估。
对患有法布里病的移植候选者进行高凝状态检测，分析其 HLA 类型、ABO 血型以及提示高凝状态的合并症。
在一组患有法布里病的白种男性肾移植受者中，记录到法布里病与活化蛋白 C 抵抗存在独特关联。五名患者中有四名是 A 血型，且无提示高凝状态的明显合并症。活化蛋白 C 抵抗（APCR）阳性患者共享 HLA 位点 -B8 和 -Dr3，而 APCR 阴性患者共享 HLA 位点 -B27 和 -B38。
鉴于在我们的法布里病队列中观察到 APCR 发生率增加，我们建议对所有法布里病患者进行 APCR 筛查。由于在血管内皮和外周血单核细胞上发现了因子 V 和因子 Va 受体，法布里病存在时的 APCR 可能是一种非免疫性的排斥刺激因素。对法布里病患者的 HLA 分型分析可能会进一步阐明基于 HLA 的法布里病关联以及活化蛋白 C 抵抗与血栓形成和排斥风险之间的关系。
