Immediate Type Hypersensitivity to Heparins: Two Case Reports and a Review of the Literature

Abstract

Immediate type hypersensitivity reactions due to heparins are rare, and the exact immunologic pathomechanism has not been identified so far. In our 2 case reports, we describe first a 50-year-old female who received dalteparin (Fragmin®) and developed signs of an immediate type hypersensitivity reaction. The personal history revealed a previous application of dalteparin (Fragmin®). Evaluation with a skin prick test showed positive results for dalteparin. The second case deals with a 73-year-old female with a suspected immediate type reaction after the administration of dalteparin (Fragmin®). A skin prick test was negative but intracutaneous tests showed a positive reaction to the causative agent. Both cases indicated cross-reactivity reactions for low-molecular-weight heparin (LMWH) but not for unfractioned heparin (UFH) or fondaparinux. In conclusion, our case reports including a review of published cases of immediate type hypersensitivity reactions after the application of heparins illustrate this rare complication. Mostly, the causative agent can be identified with a skin test, which is highly suggestive of an IgE-mediated reaction. Therapeutic alternatives for patients with sensitization to an LMWH are UFH and fondaparinux. Both agents have a small risk of cross-reactivity compared to heparins of the same substance class.

Recent Advances in Clinical Allergy and Immunology

“…In cases of rare, immediate-type reactions to heparins that can be identified by skin prick testing, alternative therapies with unfractionated heparins or fondaparinux have been recommended [93]. …”

Hypersensitivity reactions to low molecular weight heparins: different patterns of cross-reactivity in 3 patients

“…The third case presents a very rare case of IHR to one LMWH with cross-reactivity to other two tested LMWHs. Literature search revealed only seven cases of proven immediate-type D r a f t hypersensitivity to the culprit LMWH where skin cross-reactivity studies were done and information on the results has been provided (Anders and Trautmann 2013;Caballero and Fernandez-Benitez 2003;González et al 2014;Harr et al 2006;Bekkenk and van Zuuren 2005;Cesana et al 2016;Kavut and Koca 2012). The cases are summarised in Table 2.…”

“…However, challenge with enoxaparin resulted in generalised urticaria, so the skin test was presumably falsely negative and the tolerance of tinzaparin could not be established since challenge test was not performed (Bekkenk and van Zuuren 2005). Cesana describes two cases of IHR to dalteparin (Cesana et al 2016). For the purpose of this review only one case (with positive skin tests to culprit drug) is considered relevant.…”

Clinical Patterns of Heparin Allergy: Cross-reactivity Between Low-Molecular-Weight Heparins and Unfractionated Heparins

“…Delayed-type hypersensitivity reactions are the most frequently reported [2]. Immediate reactions to UFH and LMWHs have also been reported [3]. Furthermore, these agents can trigger type 2 hypersensitivity reactions (thrombocytopenia) and type 3 reactions (Arthus reaction) [4].…”

“…Owing to lyonization, X-linked CGD carriers (XL-CGD) have a dual phagocyte population, with 20% to 80% functioning phagocytes. Neutrophils with inactivation of the mutated X chromosome in the CYBB gene have a normal respiratory burst, whereas neutrophils with inactivation of the normal X chromosome have a CGD phenotype [1][2][3].…”