Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia - Results of the PARKAA study
Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia - Results of the PARKAA study
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DOI：
10.1160/th02-11-0283
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发表时间：
2003-08-01
影响因子：
6.7
通讯作者：
Mikulis, D
中科院分区：
文献类型：
--
作者：
Mitchell, L;Andrew, M;Mikulis, D
据报道，急性淋巴细胞白血病（ALL）儿童血栓形成事件与使用L-天冬酰胺酶（ASP）之间存在相关性。血栓形成的机制可能与获得性抗凝血酶缺乏症有关。由于使用抗凝血酶浓缩物进行一级预防可预防血栓形成，因此进行了PARKAA（在接受L-天冬酰胺酶治疗的ALL儿童中进行预防性抗凝血酶替代治疗）研究。PARKAA的目的是确定抗凝血酶治疗的疗效和安全性是否存在趋势，通过1）血栓形成发生率2）出血发生率和3）内源性凝血酶生成的血浆标志物作为血栓形成的替代结局进行评估。该研究没有能力回答疗效和安全性问题，而是检测趋势。PARKAA是一项在接受ASP治疗的ALL儿童中进行的开放、随机、对照研究。儿童随机接受抗凝血酶输注或不接受抗凝血酶治疗。所有血栓形成事件均通过双侧静脉造影、超声、超声心动图和MRI证实。接受抗凝血酶治疗的患者血栓形成的发生率为28%（95%CI 10-46%），而未接受治疗的患者为37%（95%CI 24-49%）。治疗组的血浆标志物无显著差异。总之，抗凝血酶浓缩物治疗显示出疗效趋势。和安全性相比之下，血栓形成的替代标志物没有差异。需要精心设计的临床试验来测试抗凝血酶在这一人群中的疗效和安全性。
An association has been reported between thrombotic events and the use of L-asparaginase (ASP) in children with acute lymphoblastic leukaemia (ALL). The mechanism for thrombosis is likely related to an acquired antithrombin deficiency. Since a primary prophylaxis using antithrombin concentrates may prevent thrombosis, the PARKAA (Prophylactic Antithrombin replacement in kids with ALL treated with L-asparaginase) study was performed. The objectives of PARKAA were to determine if there was a trend to efficacy and safety of antithrombin treatment as assessed by 1) incidence of thrombosis 2) incidence of bleeding and 3) plasma markers of endogenous thrombin generation as surrogate outcomes for thrombosis. The study was not powered to answer the question of efficacy and safety, but rather to detect a trend. PARKAA was an open, randomised, controlled study in children with ALL being treated with ASP. Children were randomised to receive antithrombin infusions or no antithrombin treatment. All thrombotic events were confirmed using bilateral venography, ultrasound, echocardiography and MRI. The incidence of thrombosis in patients treated with antithrombin was 28% (95% Cl 10-46%), compared to 37% (95% Cl 24-49%) in the non treated arm. Two minor bleed's occurred in patients in the treated arm, but were not considered to be related to antithrombin. No significant differences were seen in plasma markers by the treatment group. In conclusion, treatment with antithrombin concentrate shows a trend to efficacy. and safety. In contrast, there was no difference in surrogate markers for thrombosis. Carefully designed clinical trials are needed to test the efficacy and safety of antithrombin in this population.