Appel Inge M, Hop Wim C J, van Kessel-Bakvis Carla, Stigter Rolinda, Pieters Rob
Department of Pediatrics, Div. Oncology/Hematology, Erasmus MC/ Sophia Children's Hospital, Rotterdam, The Netherlands.
Thromb Haemost. 2008 Aug;100(2):330-7.
Alterations in haemostasis are frequently observed in children with acute lymphoblastic leukemia (ALL). It was the objective of this study to analyse age-related disturbances in coagulation and fibrinolysis parameters during the induction phase of the antileukemic treatment. Sixty-four children were classified by age into three groups (1-5, 6-10, 11-16 years), and studied during induction treatment of ALL including four weeks of dexamethasone, followed by two weeks tapering of dexamethasone during which 6,000 IU/m(2) native L-Asparaginase (total 4 doses) was administered intravenously twice weekly. Blood samples were collected immediately before each L-Asparaginase infusion to analyze procoagulant (fibrinogen, factor [F] II, FV, FVII, F IX, F X) and anticoagulant factors (antithrombin [AT], protein C, protein S), parameters of thrombin generation (F1+2, TAT) and fibrinolysis (alpha2-antiplasmin, plasminogen, PAP, D-dimer). Children were in a hypercoagulable state after four weeks of dexamethasone due to upregulation of coagulation parameters. Upregulation was highest in the two youngest age groups. During L-Asparaginase treatment the 11- to 16-year-olds showed lower values in procoagulant and, even more, in anticoagulant factor levels compared to the younger children. Activation markers of thrombin generation and fibrinolysis did not change over time during the study period. Decreased synthesis of alpha2-antiplasmin and plasminogen during L-Asparaginase treatment resulted in less potential of clot lysis by plasmin in children older than 11 years of age. In conclusion, a more severe decline of anticoagulant and fibrinolytic parameters in children between 11 and 16 years of age underline that these children are at higher risk of thrombosis during ALL induction treatment.
急性淋巴细胞白血病（ALL）患儿常出现止血功能改变。本研究的目的是分析抗白血病治疗诱导期与年龄相关的凝血和纤溶参数紊乱情况。64名儿童按年龄分为三组（1 - 5岁、6 - 10岁、11 - 16岁），在ALL诱导治疗期间进行研究，包括四周的地塞米松治疗，随后地塞米松逐渐减量两周，在此期间每周两次静脉注射6000 IU/m²天然L - 天冬酰胺酶（共4剂）。在每次注射L - 天冬酰胺酶前立即采集血样，分析促凝因子（纤维蛋白原、因子[F]II、FV、FVII、FIX、FX）和抗凝因子（抗凝血酶[AT]、蛋白C、蛋白S）、凝血酶生成参数（F1 + 2、TAT）和纤溶参数（α2 - 抗纤溶酶、纤溶酶原、PAP、D - 二聚体）。四周地塞米松治疗后，由于凝血参数上调，儿童处于高凝状态。上调在两个最年幼的年龄组中最为明显。在L - 天冬酰胺酶治疗期间，11至16岁的儿童与年幼儿童相比，促凝因子水平较低，抗凝因子水平更低。在研究期间，凝血酶生成和纤溶的激活标志物随时间没有变化。L - 天冬酰胺酶治疗期间α2 - 抗纤溶酶和纤溶酶原合成减少，导致11岁以上儿童纤溶酶溶解血栓的潜力降低。总之，11至16岁儿童抗凝和纤溶参数更严重的下降表明，这些儿童在ALL诱导治疗期间发生血栓形成的风险更高。
