Abstract

Non-immediate allergic reactions to unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are varied in presentation, and include local painful, erythematous plaques at injection sites, generalized rashes, or heparin-induced thrombocytopaenia. To investigate these, intradermal testing or subcutaneous challenge with heparins are commonly performed. We present two female patients with a history of large painful, pruritic, erythematous plaques at abdominal injection sites, 48 hours after administration of heparin derivatives. Patient 1, a 64-year-old on warfarin for recurrent deep vein thrombosis (DVT) and pulmonary embolism, presented with previous reactions to subcutaneous (s.c.) enoxaparin and dalteparin during a period of subtherapeutic INR levels. No skin testing was performed. A graded subcutaneous challenge to danaparoid resulted in a severe local reaction. Subcutaneous UFH challenge initially resulted in minimal erythema at the injection site, therefore a graded intravenous (IV) challenge was initiated. However, generalised pruritus, headache and nausea was reported within 1 hour of the full intravenous dose and an extensive cutaneous reaction at the initial s.c. injection site developed. Patient 2, a 41-year-old female, developed non-immediate allergic reactions to UFH given for DVT prophylaxis, and later against enoxaparin, given for DVT treatment. Skin testing was performed and intradermal delayed reading (at 48 hours; 1:10 dilution) to heparin, enoxaparin, dalteparin, danaparoid and fondaparinux revealed positive reactions to all tested except to danaparoid and fondaparinux. A subcutaneous danaparoid challenge was unsuccessful. Both patients underwent a fondaparinux challenge, with subcutaneous administration of treatment doses demonstrating no evidence of non-immediate reactions. A high rate of cross-reactivity between UFH, LWMH and the semi-synthetic heparinoids has been reported, and the fully synthetic anticoagulant fondaparinux has been identified as a useful alternative in approximately 45 cases in the literature. Fondaparinux can be a useful alternative in cases of heparin and heparinoid non-immediate allergy.

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