Effect of dalteparin, a low-molecular-weight heparin, as adjunctive therapy in patients with Kawasaki disease: a retrospective study

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.