Safety and Efficacy of Danaparoid (Orgaran^®) Use in Children

Abstract

Immune-mediated heparin-induced thrombocytopenia (HIT) is an uncommon but serious complication of therapy with heparins. It affects all ages and requires replacement of the causative anticoagulant. However, information on alternative antithrombotic use in children with HIT is limited. This paper reviews 27 published and 7 unpublished case reports of children aged 2 weeks to 17 years treated with danaparoid. Thirty-three suffered from HIT or suspected HIT, and 1 child without HIT had a high bleeding risk. All children had severe underlying problems increasing their thrombotic and/or bleeding risk. HIT diagnosis was confirmed serologically or clinically in 26 cases (78.8%). Danaparoid regimens were similar to those used in adults, but in general, younger children needed higher daily doses of danaparoid to achieve the same target plasma anti-Xa levels than teenagers or adults. Of those with a known outcome 28/33 children (84.8%) survived, 7 having suffered from a serious adverse event. Five deaths occurred including 1 thrombotic and 2 major bleeds. Three of the in total 4 major bleeding events occurred in children undergoing surgery with cardiopulmonary bypass. We conclude that despite the reported adverse events danaparoid can be used as an alternative antithrombotic for children who are intolerant of the heparins, except in cases requiring cardiopulmonary bypass surgery.

Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children

“…No data are available about potential association with comorbid conditions or transient risk factors that may trigger recurrence, especially in patients receiving suboptimal therapy. Interestingly, heparin‐induced thrombocytopenia has not been reported following the sole use of LMWH in children ( Ranze et al , 1999 ; Newall et al , 2003 ; Bidlingmaier et al , 2006 ).…”

“…No data are available about potential association with comorbid conditions or transient risk factors that may trigger recurrence, especially in patients receiving suboptimal therapy. Interestingly, heparin-induced thrombocytopenia has not been reported following the sole use of LMWH in children (Ranze et al, 1999;Newall et al, 2003;Bidlingmaier et al, 2006). The overall major bleeding rate under LMWH administration in children was 3%, ranging from 0 to 5% for enoxaparin (Streif et al, 2003;Dix et al, 2000;Punzalan et al, 2000;Ho et al, 2004, Michaels et al, 2004, 3% for tinzaparin (Kuhle et al, 2005) and 5.6% for reviparin-sodium (Massicotte et al, 2003a).…”

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

“…Three patients, ranging in age from 2 months to 14 years, were identified. [429][430][431] Two of these 3 patients survived. Danaparoid is not available for use in the United States.…”

Prevalence of heparin-dependent platelet antibodies in children after cardiopulmonary bypass*

“…Typical options include direct thrombin inhibitors such as lepirudin and argatroban or a heparinoid such as danaparoid. There is less familiarity in using these agents in children (33)(34)(35)(36)(37)(38)(39), and adverse effects such as major bleeding have been reported (37)(38)(39). In addition, danaparoid, which is currently not available in the United States, has been associated with in vivo HDPA cross-reactivity of four of 33 (12%) (38).…”