Kirschke R, Nürnberger W, Eckhof-Donovan S, Nürnberger I, Göbel U
Department of Pediatric Haematology and Oncology, Heinrich Heine University Medical Center, Düsseldorf, Germany.
Klin Padiatr. 1998 Jul-Aug;210(4):285-90. doi: 10.1055/s-2008-1043893.
The etiology of thrombo-embolic events after therapy with asparaginase (ASP) is not fully understood. To investigate if cytotoxic drugs given in combination with asparaginase (ASP) have an additional effect on the coagulation system, a detailed analysis of coagulation factors was performed. Therefore, we investigated two combinations of the COALL-05-92-protocol, [cylophosphamide]/methotrexate/ASP ([CYC]/MTX/ASP) and high dose arabinoside/ASP (HIDAC/ASP). In 33 children with acute lymphoblastic leukaemia the following parameters were determined: plasminogen-activator-inhibitor-1, plasminogen, antiplasmin, protein C, antithrombin, modified antithrombin, prothrombin-fragments 1 + 2 and thrombinantithrombin-complex. All children had an indwelling catheter. The most distinctive result of this investigation is that plasminogen shows a deeper and longer lasting decrease in the [CYC]/MTX/ASP-combination (median 65% NHP) compared to the HIDAC/ASP-combination (median 105% NHP) (p = 0.01). The other parameters showed the characteristic changes after ASP-therapy. None of our patients developed any clinical signs of thrombosis, even though two patients showed four altered coagulation parameters on the same day. This shows, that the coexistence of indwelling catheters plus four decreased coagulation parameters does not necessarily imply the development of thrombosis. We conclude that the parameters measured in this study do not sufficiently predict the development of thrombosis.
天冬酰胺酶（ASP）治疗后血栓栓塞事件的病因尚未完全明确。为了研究细胞毒性药物与天冬酰胺酶（ASP）联合使用是否会对凝血系统产生额外影响，我们对凝血因子进行了详细分析。因此，我们研究了COALL - 05 - 92方案的两种联合用药，即环磷酰胺/甲氨蝶呤/天冬酰胺酶（[CYC]/MTX/ASP）和大剂量阿糖胞苷/天冬酰胺酶（HIDAC/ASP）。我们测定了33例急性淋巴细胞白血病患儿的以下参数：纤溶酶原激活物抑制剂-1、纤溶酶原、抗纤溶酶、蛋白C、抗凝血酶、改良抗凝血酶、凝血酶原片段1 + 2和凝血酶-抗凝血酶复合物。所有患儿均留置了导管。本研究最显著的结果是，与HIDAC/ASP联合用药组（中位数105%正常血浆水平）相比，[CYC]/MTX/ASP联合用药组的纤溶酶原水平下降幅度更深且持续时间更长（中位数65%正常血浆水平）（p = 0.01）。其他参数在ASP治疗后呈现出特征性变化。尽管有两名患者在同一天出现了四项凝血参数改变，但我们的患者均未出现任何血栓形成的临床症状。这表明，留置导管并存加上四项凝血参数降低并不一定意味着会发生血栓形成。我们得出结论，本研究中所测定的参数不足以预测血栓形成的发生。
