低分子量肝素达肝素作为辅助治疗川崎病患者的疗效：一项回顾性研究。
Effect of dalteparin, a low-molecular-weight heparin, as adjunctive therapy in patients with Kawasaki disease: a retrospective study.
机构信息
Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
出版信息
BMC Pediatr. 2014 Jan 30;14:27. doi: 10.1186/1471-2431-14-27.
BACKGROUND
Dalteparin, a low-molecular-weight heparin, has anticoagulant and anti-angiogenic activity. This study investigated whether dalteparin reduced coronary artery lesion (CAL) prevalence, and resistance to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD).
METHODS
This retrospective study comprised two parts. In the first cohort, 126 patients with KD (68 male, 58 female; median age: 22 months, range: 1-67 months) admitted to Nihon University Nerima-Hikarigaoka Hospital from January 2004 to June 2008, received either dalteparin 75 IU/kg/day, IVIG 400 mg/kg/day for 5 consecutive days, and aspirin 30 mg/kg/day, or dalteparin 75 IU/kg/day and aspirin 30 mg/kg/day, until clinical improvement. Control data came from the 2005-6 Nationwide KD survey. In the second cohort, 112 patients with KD (59 male, 53 female; median age: 19 months, range: 1-66 months) admitted from June 2010 to February 2012, received either dalteparin 75 IU/kg/day, IVIG 2.0 g/kg over 12 h, and aspirin 30 mg/kg/day, or dalteparin 75 IU/kg/day and aspirin 30 mg/kg/day. Control data came from the 2009-10 Nationwide KD survey. No patients enrolled in the nationwide surveys received dalteparin. All patients at our institution were given dalteparin in their combination therapy.
RESULTS
A comparison of the first cohort with controls in the nationwide survey showed that the prevalence of initial administration of IVIG was 80.2% versus 86.0%; the rate of additional IVIG administration was 7.1% versus 14.0% (p = 0.03); CAL prevalence in the acute period was 4.8% versus 11.9% (p < 0.01); and the prevalence of cardiovascular sequelae was 0% versus 3.8% (p < 0.05). A comparison of the second cohort with controls in the nationwide survey showed that the rate of initial administration of IVIG was 92.9% versus 89.5%; the rate of additional IVIG administration was 8.9% versus 17.1% (p = 0.02); the prevalence of resistance to IVIG was 3.6% versus 14.9% (p < 0.001); and CAL prevalence in the acute period was 2.7% versus 8.6% (p = 0.03).
CONCLUSIONS
This study found that adjunctive dalteparin was associated with a lower prevalence of IVIG resistance and CAL in young children with KD.
TRIAL REGISTRATION UMIN-CTR: UMIN000010349.
背景
达肝素是一种低分子肝素，具有抗凝和抗血管生成活性。本研究旨在探讨达肝素是否降低川崎病（KD）患者冠状动脉病变（CAL）的发生率和对静脉注射免疫球蛋白（IVIG）治疗的抵抗。
方法
本回顾性研究分为两部分。第一部分纳入了 2004 年 1 月至 2008 年 6 月期间在日本大学日比谷医院接受治疗的 126 例 KD 患儿（男 68 例，女 58 例；中位年龄 22 个月，范围 1-67 个月）。他们接受了达肝素 75 IU/kg/天、IVIG 400 mg/kg/天连续 5 天，同时服用阿司匹林 30 mg/kg/天，或达肝素 75 IU/kg/天联合阿司匹林 30 mg/kg/天。对照组数据来自 2005-2006 年全国性 KD 调查。第二部分纳入了 2010 年 6 月至 2012 年 2 月期间在我院接受治疗的 112 例 KD 患儿（男 59 例，女 53 例；中位年龄 19 个月，范围 1-66 个月）。他们接受了达肝素 75 IU/kg/天、IVIG 2.0 g/kg 于 12 小时内输注，同时服用阿司匹林 30 mg/kg/天，或达肝素 75 IU/kg/天联合阿司匹林 30 mg/kg/天。对照组数据来自 2009-2010 年全国性 KD 调查。我院的所有患者均在联合治疗中使用了达肝素。
结果
与全国性调查中的对照组相比，第一部分患儿中 IVIG 初始治疗的使用率为 80.2% vs. 86.0%；额外 IVIG 治疗的使用率为 7.1% vs. 14.0%（p=0.03）；急性期 CAL 的发生率为 4.8% vs. 11.9%（p<0.01）；心血管后遗症的发生率为 0% vs. 3.8%（p<0.05）。与全国性调查中的对照组相比，第二部分患儿中 IVIG 初始治疗的使用率为 92.9% vs. 89.5%；额外 IVIG 治疗的使用率为 8.9% vs. 17.1%（p=0.02）；IVIG 抵抗的发生率为 3.6% vs. 14.9%（p<0.001）；急性期 CAL 的发生率为 2.7% vs. 8.6%（p=0.03）。
结论
本研究发现，KD 患儿联合使用达肝素可降低 IVIG 抵抗和 CAL 的发生率。
临床试验注册号
UMIN000010349。
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