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

Inamo, Yasuji; Saito, Kei; Hasegawa, Maki; Hayashi, Ryohei; Nakamura, Takahiro; Abe, Osamu; Ishikawa, Takeko; Yoshino, Yayoi; Hashimoto, Koji; Fuchigami, Tatsuo

doi:10.1186/1471-2431-14-27

Cited by 12 publications

(6 citation statements)

References 22 publications

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“…A recent study reported that 81% of patients with KD who eventually developed coronary aneurysms showed coronary abnormalities on their initial echocardiograms [ 12 ]. Studies have proposed the use of adjuvant therapies with agents such as atorvastatin [ 13 ], steroids [ 14 , 15 ], and dalteparin [ 16 ] to ameliorate the CALs of patients with KD during the acute KD phase. Friedman et al [ 17 ] demonstrated that the rate of coronary aneurysm regression was significantly higher in patients with KD receiving IVIG and adjunctive medications than in those not receiving such medications (91% vs 68%, P = 0.02).…”

Section: Discussionmentioning

confidence: 99%

Risk factors and implications of progressive coronary dilatation in children with Kawasaki disease

Liu

et al. 2017

BMC Pediatr

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Background: Kawasaki disease (KD) is an acute systemic vasculitis that occurs in children and may lead to cardiovascular morbidity and mortality. Progressive coronary dilatation for at least 2 months is associated with worse late coronary outcomes in patients with KD having medium or giant aneurysms. However, the risk factors and occurrence of progressive coronary dilatation in patients with KD but without medium or giant aneurysms have been insufficiently explored. Methods: We retrospectively enrolled 169 patients with KD from a tertiary medical center in Taiwan during [2009][2010][2011][2012][2013]. Medical records of all patients were reviewed. Echocardiography was performed during the acute KD phase and at 3-4 weeks, 6-8 weeks, 6 months, and 12 months after KD onset. Progressive coronary dilatation was defined as the progressive enlargement of coronary arteries on three consecutive echocardiograms. Logistic regression analysis was conducted to evaluate the potential risk factors for coronary aneurysms and progressive coronary dilatation. Results: Of a total of 169 patients with KD, 31 (18.3%) had maximal coronary Z-scores of ≥ + 2.5 during the acute KD phase, 16 (9.5%; male/female: 9/7) had coronary aneurysms at 1 month after KD onset, and 5 (3.0%) satisfied the definition of progressive coronary dilatation. Multivariate logistic regression analysis revealed that an initial maximal coronary Z-score of ≥ + 2.5 [odds ratio (OR): 5.24, 95% confidence interval (CI): 1.31-21.3, P = 0.020] and hypoalbuminemia (OR: 4.83, 95% CI: 1.11-20.9, P = 0.035) were independent risk factors for coronary aneurysms and were significantly associated with progressive coronary dilatation. However, the association between intravenous immunoglobulin unresponsiveness and the development of coronary aneurysms at 1 month after KD onset didn't reach the level of significance (P = 0.058). Conclusions: In the present study, 3% (5/169) of patients with KD had progressive coronary dilatation, which was associated with persistent coronary aneurysms at 1 year after KD onset. Initial coronary dilatation and hypoalbuminemia were independently associated with the occurrence of progressive coronary dilatation. Therefore, such patients may require intensive cardiac monitoring and adjuvant therapies apart from immunoglobulin therapies.

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Section: Discussionmentioning

confidence: 99%

Risk factors and implications of progressive coronary dilatation in children with Kawasaki disease

Liu

et al. 2017

BMC Pediatr

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“…reported the use of continuous intravenous infusion of dalteparin and oral aspirin with and without intravenous immunoglobulin (IVIG) in two retrospective cohorts of 238 Japanese children with Kawasaki's disease. They concluded that the antiangiogenic activity of adjunctive dalteparin was associated with a lower prevalence of coronary artery lesions and IVIG resistance .…”

Section: Introductionmentioning

confidence: 99%

Multicenter dose‐finding and efficacy and safety outcomes in neonates and children treated with dalteparin for acute venous thromboembolism

O’Brien

Kulkarni

Wallace

et al. 2014

Journal of Thrombosis and Haemostasis

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NA. Multicenter dose-finding and efficacy and safety outcomes in neonates and children treated with dalteparin for acute venous thromboembolism. J Thromb Haemost 2014; 12: 1822-5.Summary. Background: Low molecular weight heparins (LMWHs) constitute the mainstay of anticoagulant therapy for pediatric venous thromboembolism (VTE). The safety and effectiveness of dalteparin, an LMWH, has not been established in children, and pediatric data on dalteparin for VTE are limited to one single-center experience. Objective: To establish dose-finding (primary endpoint) and efficacy/safety outcomes (secondary endpoints) in children treated with dalteparin in a substudy of the Kids-DOTT trial. Patients and methods: A prospective multicenter trial using dalteparin subcutaneously twice daily for acute VTE in children aged ≤ 21 years was conducted under an investigator-held Investigational New Drug application registered with the US Food and Drug Administration. Initial weight-based dosing per protocol was as follows: infants (< 12 months), 150 IU kg À1 ; children (1-12 years), 125 IU kg À1 ; and adolescents (13-18 years), 100 IU kg À1. Bleeding events were categorized according to ISTH criteria. Descriptive non-parametric statistics were employed for all analyses. Results: Eighteen patients (67% male) were enrolled from January 2010 to October 2013 across four centers. No supratherapeutic levels were observed. Median (range) therapeutic doses by age group were as follows: infants (n = 3), 180 IU kg was 48 days (range: 2-169 days), and the median followup was 10.5 months (range: 2-35 months). There were no related serious adverse events, no clinically relevant bleeding events, and no symptomatic recurrent VTEs. Conclusion: Dalteparin successfully achieved targeted antifactor Xa levels in 18 children and young adults with acute VTE with a standardized age-based dosing regimen, with a favorable safety and efficacy profile.

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“…They found a lower risk of coronary artery lesions within the first month (OR: 0.34; 95% CIL 0.17‐0.66) (low certainty of evidence) and decreased odds of needing additional treatment for refractory disease (OR: 0.48; 95% CI: 0.30‐0.76) (low certainty of evidence). There was no statistically significant difference in the odds of having a coronary artery lesion persist longer than 1 month when pooling their two cohorts (OR: 0.21; 95% CI: 0.04‐1.03) (low certainty of evidence) ( 47 ) (Tables 2 and 3 ).…”

Section: Resultsmentioning

confidence: 99%

Kawasaki Disease: A Systematic Review and Meta‐Analysis of Benefits and Harms of Common Treatments

James

Kalot

Husainat

et al. 2021

ACR Open Rheumatology

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Objective Kawasaki disease (KD) is a self‐limited vasculitis affecting medium‐sized vessels with a predilection for the coronary arteries. Although treatment reduces the likelihood of developing of coronary artery aneurysms, 5% of patients still develop aneurysms despite treatment, making KD the leading cause of acquired heart disease in children in the United States. Consequently, there is a great deal of interest in optimizing treatment regimens, particularly for higher‐risk patients, to decrease morbidity. The aim of this systematic review is to support the development of the American College of Rheumatology/Vasculitis Foundation for the diagnosis and management of KD, focusing on the more complex scenarios in which rheumatologists may become involved, such as high‐risk and refractory disease. Methods Eighty‐nine articles were considered for full review in this systematic literature review to address 16 Population, Intervention, Comparison, and Outcome questions related to KD. Data were abstracted in hierarchical fashion. Randomized control trials (RCTs) were considered first; if none were identified or if they contained insufficient information, comparative observational studies were then viewed, followed by single‐arm observational studies/single arms from comparative studies. Only observational studies with more than 10 subjects with vasculitis were included. Results Eight RCTs and 28 observational studies that addressed the questions were identified. Two questions were addressed by RCTs, seven questions had at least some comparative observational studies, three questions were only addressed by single‐arm data, and four questions had no relevant studies. Conclusion This systematic review evaluates the benefits and harms of treatments for KD beyond first‐line therapy.

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

Cited by 12 publications

References 22 publications

Risk factors and implications of progressive coronary dilatation in children with Kawasaki disease

Risk factors and implications of progressive coronary dilatation in children with Kawasaki disease

Multicenter dose‐finding and efficacy and safety outcomes in neonates and children treated with dalteparin for acute venous thromboembolism

Kawasaki Disease: A Systematic Review and Meta‐Analysis of Benefits and Harms of Common Treatments

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