Department of Dermatology and Allergy, University Hospital Würzburg, Würzburg, Germany.
Department of Dermatology and Allergy, University Hospital Würzburg, Würzburg, Germany.
J Allergy Clin Immunol Pract. 2022 Nov;10(11):2977-2983.e1. doi: 10.1016/j.jaip.2022.06.030. Epub 2022 Jul 2.
Heparin allergy most frequently manifests as delayed-type hypersensitivity (DTH) causing an itchy inflammatory skin reaction at the site of subcutaneous injection. An important differential diagnosis is circumscribed skin necrosis due to heparin-induced thrombocytopenia.
An inflammatory skin reaction to subcutaneously injected heparin generally entails the quest for alternative anticoagulation; concerns may particularly arise in an emergency situation requiring intravenous heparin administration.
All heparin DTH cases seen in our department over the last 17 years underwent standardized allergy diagnostics including challenge testing, that is, subcutaneous injection of fondaparinux and intravenous administration of unfractionated heparin (UFH).
Of a total of 50 patients with confirmed heparin allergy, DTH was found in 48 (96.0%), and immediate-type, presumably IgE-mediated hypersensitivity was diagnosed in only 2 (4.0%). In the 48 DTH cases, intradermal testing revealed broad cross-reactivity between UFH and low-molecular-weight heparins (LMWH) including nadroparin, dalteparin, and enoxaparin. Cross-reactivity with (or concomitant sensitization to) fondaparinux was seen in only 3 (6.3%) cases. Intravenous administration of UFH was tolerated by all 45 patients challenged, despite DTH to UFH and LMWH as demonstrated by intradermal testing.
If an inflammatory skin reaction at the site of subcutaneously injected heparin is observed or reported without any evidence of skin necrosis or thrombocytopenia, intravenous administration of UFH seems to be sufficiently safe and may be considered without allergy testing if urgently indicated in an emergency situation. Fondaparinux is the most suitable alternative for subcutaneous application.
肝素过敏最常表现为迟发型超敏反应（DTH），导致皮下注射部位出现瘙痒性炎症反应。一个重要的鉴别诊断是肝素诱导的血小板减少症引起的局限性皮肤坏死。
皮下注射肝素引起的炎症性皮肤反应通常需要寻找替代抗凝剂；在需要静脉内给予肝素的紧急情况下，可能会特别引起关注。
在过去 17 年中，我们科室所有确诊的肝素过敏患者均进行了标准化过敏诊断，包括挑战测试，即皮下注射磺达肝素和静脉内给予未分馏肝素（UFH）。
在总共 50 例确诊肝素过敏的患者中，DTH 见于 48 例（96.0%），仅有 2 例（4.0%）诊断为即刻型、推测为 IgE 介导的超敏反应。在 48 例 DTH 病例中，皮内试验显示 UFH 和低分子量肝素（LMWH）之间存在广泛的交叉反应，包括那屈肝素、达肝素和依诺肝素。仅在 3 例（6.3%）病例中观察到与磺达肝素（或同时致敏）的交叉反应。尽管皮内试验显示对 UFH 和 LMWH 存在 DTH，但所有接受挑战的 45 例患者均耐受静脉内给予 UFH。
如果观察到或报告皮下注射肝素部位出现炎症性皮肤反应，而无皮肤坏死或血小板减少的任何证据，则静脉内给予 UFH 似乎足够安全，如果在紧急情况下紧急需要，可在无需过敏测试的情况下考虑使用。磺达肝素是皮下应用的最佳替代药物。
