Brandão Leonardo R, Kletzel Morris, Boulad Farid, Kurtzberg Joanne, Maloney Kelly, Fligman Igal, Sison Cristina P, Dimichele Donna
Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada.
Pediatr Blood Cancer. 2008 Jun;50(6):1240-6. doi: 10.1002/pbc.21473.
Thrombotic complications occur in adult patients undergoing stem cell transplantation (SCT), especially following high dose chemo-radiotherapy. There is little published information in children on the impact of SCT on coagulation, as well as potential correlations between altered coagulation and SCT-associated thrombosis and organ failure.
Forty three pediatric subjects who underwent allogeneic SCT were prospectively evaluated for congenital thrombophilia, anticoagulant levels, coagulation activation, and fibrinolysis at pre-established set points encompassing the period from the 2 to 4 weeks prior to conditioning to 28 days post-transplantation.
A significant decrease of protein C and antithrombin levels was found in 39% and 31% of subjects respectively, between SCT days +6 and +7. A peak in plasminogen activator inhibitor-1 levels in 31% of subjects was noted between days +9 and +10. No subject experienced a thrombotic event or other SCT-related organ failure. Antithrombin deficiency correlated with underlying malignancy, donor HLA-mismatch, and TBI, whereas decreased PC activity demonstrated a trend of association with lack of T-cell depletion and TBI. Prophylactic heparin did not influence the pattern of acquired hemostatic abnormalities observed in this cohort.
Children undergoing allogeneic SCT develop a state of acquired thrombophilia in the early post-transplantation period. Although no SCT-related thromboembolic events were observed, our results provide new information about the hemostatic changes in children undergoing allogeneic SCT and their potential clinical triggers. The significance of these findings requires further prospective evaluation in a larger cohort of patients.
血栓形成并发症发生在接受干细胞移植（SCT）的成年患者中，尤其是在大剂量放化疗之后。关于SCT对儿童凝血功能的影响，以及凝血功能改变与SCT相关血栓形成和器官衰竭之间的潜在相关性，鲜有公开报道。
对43例接受异基因SCT的儿科患者进行前瞻性评估，在预定的时间点检测先天性血栓形成倾向、抗凝剂水平、凝血激活和纤维蛋白溶解情况，时间范围从预处理前2至4周直至移植后28天。
分别在39%和31%的患者中发现，在SCT后第6天和第7天之间，蛋白C和抗凝血酶水平显著下降。在31%的患者中，在第9天和第10天之间观察到纤溶酶原激活物抑制剂-1水平达到峰值。没有患者发生血栓事件或其他与SCT相关的器官衰竭。抗凝血酶缺乏与潜在恶性肿瘤、供体HLA不匹配和全身照射相关，而蛋白C活性降低显示出与缺乏T细胞清除和全身照射相关的趋势。预防性肝素并未影响该队列中观察到的获得性止血异常模式。
接受异基因SCT的儿童在移植后早期会出现获得性血栓形成倾向状态。尽管未观察到与SCT相关的血栓栓塞事件，但我们的结果提供了关于接受异基因SCT儿童止血变化及其潜在临床触发因素的新信息。这些发现的意义需要在更大规模的患者队列中进行进一步的前瞻性评估。
