左旋门冬酰胺酶导致急性淋巴细胞白血病患儿出凝血异常的探讨

Effect of L-asparaginase on Coagulation Abnormatities in Children with Acute Lymphoblastic Leukemia

目的分析急性淋巴细胞白血病(ALL)患儿应用左旋门冬酰胺酶(L-asp)所致的出凝血改变、相关原因及对策。方法前瞻性收集北京儿童医院血液病中心应用L-asp的ALL患儿51例,1)分析应用L-asp前、中、后出凝血指标:部分凝血活酶时间(APTT)、凝血酶原时间(PT)、纤维蛋白原(Fib)和抗凝血酶(AT)变化,并比较不同化疗强度(高、标危方案)和不同化疗阶段(第1、2、3次应用)出凝血指标变化;2)分析出凝血变化与血小板、D-二聚体和肝损害的相关性;3)探讨预防性输注新鲜冰冻血浆或纤维蛋白原的意义。结果51例患儿中,1)应用L-asp中、后期,Fib和AT值显著降低,但不同化疗强度和不同化疗阶段对L-asp中、后出凝血指标变化无明显影响。2)应用L-asp中、后期,血小板、D-二聚体、谷丙转氨酶(GPT)、谷草转氨酶(GOT)和肝脂肪变性与应用前相比无显著性改变。3)进行预防性补充输注的病人无血栓、出血并发症发生。结论ALL患儿应用L-asp后Fib和AT显著下降;其改变与化疗强度、化疗阶段、凝血因子消耗及肝功能损伤无明显相关;预防性补充输注可能会减少血栓/出血并发症。

Objective To analyze the alterations and the causes of coagulation in children with acute lymphoblastic leukemia （ ALL ） during L - asparaginase （ L - asp ） treatment and to find out the solutions . Methods 51 ALL patients were analyzed prospectively with 1） changes of APTT, PT, Fib and AT before, during and after treatment of L-asp; comparing the changes different protocols and in different periods of chemotherapy; 2） the relationship between coagulation and changes of platelet and D-dimer as well as liver function. 3） the significance of supplementary therapy in patients with lower AT and/or Fib. Results 1） Fib and AT were significantly decreased during and at the end of L-asp treatment, but not influenced much by intensity and stages of chemotherapy. 2） There were no significant changes of platelets, D-dimer and liver function during and at the end of L-asp. 3） No thrombosis or hemorrhage occurring after prophylactic supplementary transfusion of AT and/or Fib. Conclusion The negative alterations of Fib and AT were significant in ALL patients during L-asp therapy; These changes were not influenced much by intensity or stages of chemotherapy, neither by liver function; The prophylactic supplementary therapy may reduce the complications of thrombosis and hemorrhage during L-asp treatment.