Increased levels of tissue factor activity and procoagulant phospholipids during treatment of children with acute lymphoblastic leukaemia
Increased levels of tissue factor activity and procoagulant phospholipids during treatment of children with acute lymphoblastic leukaemia
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DOI：
10.1111/j.1365-2141.2009.07958.x
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发表时间：
2010-02-01
影响因子：
6.5
通讯作者：
Vasse, Marc
中科院分区：
文献类型：
--
作者：
Schneider, Pascale;Van Dreden, Patrick;Vasse, Marc
在患有急性淋巴细胞白血病 (ALL) 的儿科患者中使用 L-天冬酰胺酶 (L-ASP) 与血栓并发症相关。我们评估了接受法国急性淋巴细胞白血病组 (FRALLE)-2000 方案治疗的 26 名连续 ALL 儿童（25 名 B-ALL 和 1 名 T-ALL）的组织因子 (TFa)、血栓调节蛋白 (TMa) 和促凝磷脂 (PPL) 的活性。在诊断时、糖皮质激素 (GC) 治疗后、l-ASP、长春新碱 (VCR) 和阿霉素 (ADR) 诱导阶段、再诱导期间和治疗后一周内采集样本。血浆TFa、TMa和PPL水平在治疗的不同阶段逐渐显着升高，在诱导期观察到较高水平，并在治疗停止后下降。体外研究表明，用于 ALL 治疗的不同药物可诱导正常和白血病血细胞 TF 和促凝血活性 (PCA) 的弱表达，而在内皮细胞上观察到明显的效果。总之，这些数据表明，除了明确的凝血因子增加和抑制剂缺乏之外，内皮损伤可能导致 TF 和 PPL 释放，并可能导致接受 ALL 治疗的儿童出现高凝状态。
The use of l-asparaginase (L-ASP) in paediatric patients with acute lymphoblastic leukaemia (ALL) is associated with thrombotic complications. We evaluated the activities of tissue factor (TFa), thrombomodulin (TMa) and procoagulant phospholipids (PPL) in 26 consecutive children with ALL (25 B-ALL and one T-ALL) treated by the French Acute Lymphoblastic Leukemia group (FRALLE)-2000 protocol. Samples were obtained at diagnosis, after glucocorticoid (GC) therapy, during the induction phase with l-ASP, vincristine (VCR) and adriamycin (ADR), during the re-induction and within the week after treatment. Plasma levels of TFa, TMa and PPL increased gradually and significantly during the different phases of the treatment, with higher levels observed during the induction period, and decreased after treatment discontinuation. In vitro studies showed that the different drugs used for ALL treatment could induce a weak expression of TF and procoagulant activity (PCA) on normal and leukaemia blood cells, while a marked effect was observed on endothelial cells. In conclusion, these data indicate that, in addition to the well-identified increased in coagulation factors and inhibitor deficiencies, the injury of the endothelium could lead to the release of TF and PPL and could contribute to the hypercoagulability of children treated for ALL.