Mitchell L G, Halton J M, Vegh P A, Barr R D, Venneri T, Pai K M, Andrew M E
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Am J Pediatr Hematol Oncol. 1994 May;16(2):120-6.
We sought to determine the effect of disease and combination chemotherapy on the hemostatic system in children with acute lymphoid leukemia (ALL).
We conducted a prospective study of children newly diagnosed with ALL. Plasma samples were obtained at four time points: at diagnosis before therapy, 5 days after administration of L-asparaginase alone, after the remission induction program, and at completion of the consolidation phase. Plasma levels of 21 hemostatic proteins were measured. The amount of thrombin generated following activation with an APTT reagent was quantitated.
At diagnosis there were significant elevations in factors VIII, IX, von Willebrand, alpha 2-macroglobulin and protein S. In contrast, there were significant reductions in protein C, prekallikrein, and factors XIIIA and XIIIS. L-asparaginase treatment alone decreased concentrations of 11 proteins, with antithrombin III being affected to the greatest extent. After multiagent chemotherapy, not including L-asparaginase, concentrations of most proteins increased to or above baseline. At completion of consolidation therapy, which included weekly L-asparaginase administration, concentrations of most proteins were decreased compared with baseline values. The amount of thrombin generated following activation with an APTT reagent was similar to adults.
Plasma concentrations of coagulation proteins are affected by disease (ALL) alone and by combination chemotherapy with or without L-asparaginase. There is no impairment of in vitro capacity to generate thrombin. L-asparaginase alone caused a decrease in almost all proteins; however, ATIII was affected to the greatest extent.
我们试图确定疾病和联合化疗对急性淋巴细胞白血病（ALL）患儿止血系统的影响。
我们对新诊断为ALL的患儿进行了一项前瞻性研究。在四个时间点采集血浆样本：治疗前诊断时、单独给予L-天冬酰胺酶5天后、缓解诱导方案后以及巩固阶段结束时。检测了21种止血蛋白的血浆水平。用活化部分凝血活酶时间（APTT）试剂激活后产生的凝血酶量进行了定量。
诊断时，因子VIII、IX、血管性血友病因子、α2-巨球蛋白和蛋白S显著升高。相比之下，蛋白C、前激肽释放酶以及因子XIIIA和XIIIS显著降低。单独使用L-天冬酰胺酶治疗使11种蛋白的浓度降低，其中抗凝血酶III受影响最大。在不包括L-天冬酰胺酶的多药化疗后，大多数蛋白的浓度升至基线水平或以上。在包括每周给予L-天冬酰胺酶的巩固治疗结束时，大多数蛋白的浓度与基线值相比降低。用APTT试剂激活后产生的凝血酶量与成人相似。
凝血蛋白的血浆浓度受疾病（ALL）本身以及含或不含L-天冬酰胺酶的联合化疗的影响。体外产生凝血酶的能力没有受损。单独使用L-天冬酰胺酶几乎使所有蛋白降低；然而，抗凝血酶III受影响最大。
