Eber S W, Gungor T, Veldman A, Sykora K, Scherer F, Fischer D, Grigull L
Division of Immunology/Hematology/BMT, University Children's Hospital, Zurich, Switzerland.
Pediatr Transplant. 2007 Feb;11(1):49-57. doi: 10.1111/j.1399-3046.2006.00612.x.
Plasminogen activator inhibitor 1 is known to be elevated in patients with hepatic VOD after intensive chemotherapy. To re-establish endogenous fibrinolysis and to inhibit thrombin formation, we used non-APC (zymogen) to normalize PAI-1 levels. As a consequence of thrombin formation inhibition and the consecutive inhibition of the coagulation cascade, this treatment is expected to reduce the elevated D-dimer level. Six pediatric stem cell recipients with moderate or severe VOD after busulfan or total body irradiation conditioning regimen are reported here who were therapy-refractory to defibrotide or rt-PA therapy. All patients had low levels of PC activity (16-39%). The administration of PC (60-240 IU/kg) led to a rapid and sustained rise in PC activity (target level >80%) with near normalization of prothrombin and partial thromboplastin time in all patients. Elevated PAI-1 levels declined. Five of the six patients showed a good clinical response with prompt resolution of clinical, sonographic, and laboratory signs of hepatic blood flow obstruction, while one patient with severe VOD, as well as concomitant liver GVHD and CMV disease, had a slow but detectable response to PC therapy. All patients survived.
已知在强化化疗后发生肝静脉闭塞病（VOD）的患者中，纤溶酶原激活物抑制剂1水平会升高。为了重建内源性纤维蛋白溶解并抑制凝血酶形成，我们使用非活化蛋白C（酶原）来使PAI-1水平正常化。由于抑制了凝血酶形成以及随后对凝血级联反应的抑制，预计这种治疗可降低升高的D-二聚体水平。本文报告了6例接受白消安或全身照射预处理方案后发生中度或重度VOD的儿科干细胞接受者，他们对去纤苷或rt-PA治疗无效。所有患者的蛋白C（PC）活性水平较低（16%-39%）。给予PC（60-240 IU/kg）后，所有患者的PC活性迅速且持续升高（目标水平>80%），凝血酶原时间和部分凝血活酶时间接近正常。升高的PAI-1水平下降。6例患者中有5例显示出良好的临床反应，肝血流梗阻的临床、超声和实验室指标迅速缓解，而1例患有严重VOD以及伴有肝移植物抗宿主病（GVHD）和巨细胞病毒（CMV）疾病的患者对PC治疗反应缓慢但可检测到。所有患者均存活。
