异基因造血干细胞移植预处理期间凝血系统的亚临床改变

Alterations in coagulation in patients during transplant conditioning regimen before allogeneic hematopoietic stem cell transplantation

目的评价异基因造血干细胞移植(allo-HSCT)患者在采用改良白消安加环磷酰胺(BU/CY)加或不加抗胸腺细胞球蛋白(ATG)方案进行预处理期间发生的凝血系统改变,以及 ATG 对凝血系统产生的影响。方法 35例血液系统恶性肿瘤患者中,19例配型全合的同胞间移植者(A 组)应用改良 BU/CY 方案,16例配型不合或非血缘移植者(B 组)应用改良 BU/CY+ATG 方案。预处理前至移植后1天(+1天),检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、血浆纤维蛋白原(Fg)含量、抗凝血酶(AT)、D-二聚体、纤维蛋白降解产物(FDP)、血小板计数(BPC)、肝脏酶学和胆红素,并观察出血症状。对于部分 APTT 延长者检测Ⅷ、Ⅸ、Ⅺ和Ⅻ因子活性。结果预处理期间,两组患者均出现了短暂的 APTT 延长及持续的 Fg 升高和 BPC 减少,B 组患者在 ATG 用药期间 Fg 和 BPC的变化更为显著,还呈 D-二聚体水平暂时性增加。APTT 延长时,内源性凝血途径因子中以 FⅫ:C 降低最为明显,FⅪ:C次之。两组患者之间,PT、FDP 和 AT 以及肝功能的变化差异无显著性,几乎均在正常水平。绝大多数患者未出现明显的出血症状。结论改良 BU/CY±ATG 方案可引起凝血系统的亚临床改变,含有 ATG 的治疗方案对凝血指标的影响更为显著。

Objective To evaluate the alterations in coagulation in patients during conditioning with modified busulfan plus cyclophosphamide （BU/CY） ± antithymocyte globulin （ATG） regimen before allogeneic hematopoietic stem cell transplantation （ allo-HSCT）, and to assess the effect of ATG on coagulation system. Methods Thirty-five patients with various hematological malignancies undergoing allo-HSCT were assessed. Of them, 19 patients with HLA-matched sibling donors （group A） were conditioned with modified BU/CY regimen, 16 with HLA-mismatched family members or HLA-matched unreleated donors （group B） were conditioned with modified BU/CY ＋ ATG regimen. Blood samples were collected before the beginning of conditioning till d ＋ 1 after allo-HSCT. The following parameters were measured： prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （Fg）, antithrombin （AT）, D-Dimer, fibrin degradation product （FDP）, platelet （BPC）, liver enzymes and bilirubin. FⅧ： C, FⅨ： C, FⅪ： C and FⅫ： C in prolonged APTT blood samples were also determined. Clinical hemorrhagic symptoms were monitored. Results During conditioning, temporary lengthening of APTT, persistent rising in Fg and declining of BPC were observed in the two groups. Alterations of Fg and BPC were more significant in group B than in group A. Transient D-Dimer increase occurred only in group B on administration of ATG. Among intrinsic pathway coagulation factors, FⅫ： C and FⅪ： C were commonly decreased while APTT prolonged. No difference between the two groups was found with regard to PT, FDP, AT and liver parameters which remained in normal ranges. Most of patients in the two groups did not have overt bleeding manifestations. Conclusions Modified BU/CY ± ATG conditioning regimen can induce subclinical alterations in coagulation. The regimen containing ATG has more significant effect on coagulation parameters,