Halton J M, Mitchell L G, Vegh P, Eves M, Andrew M E
Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada.
Am J Hematol. 1994 Nov;47(3):157-61. doi: 10.1002/ajh.2830470302.
L-Asparaginase (ASP), a chemotherapeutic agent used in the treatment of children with acute lymphoblastic leukaemia (ALL), is linked to thromboembolic complications secondary to an acquired deficiency of antithrombin III (ATIII). Fresh frozen plasma (FFP) is used to prevent and/or treat thrombotic complications in these children. However, the effect of FFP on plasma concentrations of ATIII and biochemical markers of activation of coagulation has never been tested. In this study, FFP (20 ml/kg) was administered to eight children with ALL receiving ASP in the consolidation phase of their treatment. Plasma samples were drawn pre-infusion, and following infusion at 1, 24, and 48 hr. Prior to the FFP infusions, plasma concentrations of prothrombin, fibrinogen, alpha 2-macroglobulin, heparin cofactor II, protein C, and protein S were similar to levels in healthy children. Only plasma concentrations of ATIII were significantly decreased (0.55 U/ml). Following FFP infusions, there was no statistical or clinically important increase in plasma concentrations of any coagulation protein at any time point. Pre-infusion plasma concentrations of markers of endogenous thrombin generation (thrombin-antithrombin III complexes (TAT)) and activation of the fibrinolytic system in response to activation of the coagulation system (D-dimer levels) were significantly increased. However, FFP had no statistical or clinically important effect on concentrations of these markers. We conclude that FFP administration for the prevention and treatment of acquired ATIII deficiency secondary to ASP has no demonstrable benefit on plasma levels of coagulation proteins and is unlikely to be of clinical benefit.
L-天冬酰胺酶(ASP)是一种用于治疗儿童急性淋巴细胞白血病(ALL)的化疗药物,与抗凝血酶III(ATIII)后天缺乏继发的血栓栓塞并发症有关。新鲜冰冻血浆(FFP)用于预防和/或治疗这些儿童的血栓形成并发症。然而,FFP对ATIII血浆浓度及凝血激活生化标志物的影响从未得到过检验。在本研究中,8名处于治疗巩固期且正在接受ASP治疗的ALL患儿接受了FFP(20 ml/kg)输注。在输注前、输注后1小时、24小时和48小时采集血浆样本。在输注FFP之前,凝血酶原、纤维蛋白原、α2-巨球蛋白、肝素辅因子II、蛋白C和蛋白S的血浆浓度与健康儿童的水平相似。只有ATIII的血浆浓度显著降低(0.55 U/ml)。输注FFP后,在任何时间点,任何凝血蛋白的血浆浓度均无统计学或临床意义上的升高。输注前内源性凝血酶生成标志物(凝血酶-抗凝血酶III复合物(TAT))和凝血系统激活后纤溶系统激活标志物(D-二聚体水平)的血浆浓度显著升高。然而,FFP对这些标志物的浓度没有统计学或临床意义上的影响。我们得出结论,输注FFP预防和治疗ASP继发的后天性ATIII缺乏对凝血蛋白的血浆水平没有明显益处,且不太可能具有临床益处。