Murdoch Children's Research Institute, Melbourne, Vic., Australia.
Br J Haematol. 2010 Jun;149(5):734-8. doi: 10.1111/j.1365-2141.2010.08163.x. Epub 2010 Mar 21.
Low molecular weight heparins (LMWHs) are commonly used in paediatric tertiary institutions for primary prophylaxis and treatment of thromboembolic events. Despite this widespread use, the therapeutic and prophylactic guidelines for LMWH therapy in children are extrapolated from adult guidelines. In fact, there is very little information regarding the pharmacokinetics, clinical effectiveness, adverse event profile and optimal dose schedule for LMWH therapy in children. This study was designed to determine whether paediatric-specific dosage requirements for LMWH are justified, by investigating the doses required to achieve target therapeutic ranges. Patients who were treated with enoxaparin between October 2003 and July 2007 were identified for inclusion in this study. One hundred forty patients had an anti-activated factor X assay result with a total of 55 (39%) patients achieving therapeutic levels 4-6 h post dose. Children younger than 1 year required the highest dose of enoxaparin/kg and highest number of dose changes to achieve the target therapeutic range. Major bleeding occurred in one patient, equating to 0.7%, with complete clot resolution recorded in 16 (11%) patients. This study demonstrated a 2-3-fold variation in individual dose requirements for LMWH in children <or=5 years of age, and further mandates the need for age-specific dosage requirements in children receiving enoxaparin.
低分子量肝素(LMWH)在儿科三级医疗机构中常用于原发性预防和治疗血栓栓塞事件。尽管广泛使用,但 LMWH 治疗的治疗和预防指南是从成人指南推断而来。实际上,关于儿童 LMWH 治疗的药代动力学、临床疗效、不良事件概况和最佳剂量方案的信息非常有限。本研究旨在通过研究达到目标治疗范围所需的剂量来确定 LMWH 儿科特定剂量要求是否合理。
本研究确定了 2003 年 10 月至 2007 年 7 月期间接受依诺肝素治疗的患者,以将其纳入本研究。共有 140 名患者进行了抗活化因子 X 检测,其中 55 名(39%)患者在给药后 4-6 小时达到治疗水平。年龄小于 1 岁的儿童需要依诺肝素/kg 的最高剂量和最多的剂量调整以达到目标治疗范围。1 名患者发生大出血,发生率为 0.7%,16 名(11%)患者完全溶解。
本研究表明,年龄在 5 岁以下的儿童对 LMWH 的个体剂量需求存在 2-3 倍的差异,进一步需要为接受依诺肝素治疗的儿童制定特定年龄的剂量要求。