Sehgal Shivali, Sharma Sunita, Chandra Jagdish, Nangia Anita
Department of Pathology, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, India.
Department of Paediatrics, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, India.
Indian J Pathol Microbiol. 2017 Jan-Mar;60(1):50-56. doi: 10.4103/0377-4929.200029.
Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy.
To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients.
Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls.
At the time of diagnosis (day 0), various coagulation parameters were tested. These were sequentially analyzed on day 14 (after the completion of L-asparaginase doses) and on day 28 of therapy (after the completion of induction). Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C (PC) activity, and protein S (PS) activity were done by a clot-based method. Antithrombin (AT) assay was performed by chromogenic method. D-dimer (D-DI), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) levels were assayed by ELISA method.
The statistical analysis was done using Statistical Package for Social Sciences version 17.0.
No major change in PT and APTT was observed during chemotherapy; however, fibrinogen levels declined significantly (P = 0.04), following L-asparaginase treatment. D-DI levels were significantly raised at diagnosis (P < 0.001) and throughout induction therapy (P < 0.001). PC, PS, and AT were reduced in the initial part of induction, followed by a rise in the second half of therapy, reaching their respective baseline levels (P < 0.05). The tPA levels were significantly reduced in the patients at diagnosis and throughout therapy (P < 0.001). PAI-1 levels were comparable to controls at presentation and showed a rising trend during therapy.
The results of this study indicated that both the malignant process and the drugs used in combined chemotherapy cause thrombin activation, decrease in natural inhibitors, and hypofibrinolysis, resulting in hypercoagulability. Thus, ALL per se is a hypercoagulable state and the prothrombotic condition at the time of diagnosis gets enhanced during induction chemotherapy.
急性淋巴细胞白血病（ALL）患儿的血栓栓塞最常发生在抗白血病治疗开始后，提示疾病与治疗之间可能存在相互作用。
研究诱导化疗对小儿ALL患者凝血参数的影响。
对37例18岁及以下新诊断的ALL患者以及30例年龄和性别匹配的对照进行评估。
在诊断时（第0天）检测各种凝血参数。在第14天（完成L-天冬酰胺酶剂量后）和治疗第28天（诱导结束后）对这些参数进行连续分析。采用基于凝血块的方法检测凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原、蛋白C（PC）活性和蛋白S（PS）活性。采用发色底物法进行抗凝血酶（AT）检测。采用ELISA法检测D-二聚体（D-DI）、组织纤溶酶原激活物（tPA）和纤溶酶原激活物抑制剂1型（PAI-1）水平。
使用社会科学统计软件包17.0进行统计分析。
化疗期间PT和APTT未观察到重大变化；然而，L-天冬酰胺酶治疗后纤维蛋白原水平显著下降（P = 0.04）。D-DI水平在诊断时显著升高（P < 0.001），且在整个诱导治疗期间均显著升高（P < 0.001）。诱导初期PC、PS和AT降低，随后在治疗后半期升高，达到各自的基线水平（P < 0.05）。患者在诊断时和整个治疗期间tPA水平显著降低（P < 0.001）。PAI-1水平在就诊时与对照组相当，且在治疗期间呈上升趋势。
本研究结果表明，恶性过程和联合化疗中使用的药物均导致凝血酶激活、天然抑制剂减少和纤溶功能减退，从而导致高凝状态。因此，ALL本身就是一种高凝状态，诊断时的血栓前状态在诱导化疗期间会增强。
