Tolerance to intravenous heparin in patients with delayed‐type hypersensitivity to heparins: a prospective study

Abstract

Intradermal tests were performed on the volar forearm and patch tests on the back after tape stripping with a series of heparin and heparinoid preparations, including UFH (heparin Delayed-type hypersensitivity to subcutaneously injected heparin is relatively common. Particularly, extensive cross-reactivity between different heparins and heparinoids often occurs. Delayed-type hypersensitivity to heparin implies the risk of a generalized eczema when heparin is administered intravenously. However, case reports demonstrated a tolerance to intravenous heparin in patients with delayed-type hypersensitivity to subcutaneous heparin, but prospective studies have not been performed. Our study group, of 28 patients with a proven delayed-type hypersensitivity to subcutaneous heparin, was challenged with intravenous heparin, which was well tolerated in all 28 patients. Therefore, in case of therapeutic necessity, the shift from subcutaneous to intravenous heparin administration is justified.

Incidence and causes of heparin-induced skin lesions

“…This is in contrast to earlier reports from many groups, including ours. 2,4,6,7,14,22 We now believe that this difference in crossreactivity is because of differences between patients in the earlier studies and in our current study. Previous reports focused on patients who presented to allergy departments for testing of suspected delayed-type hypersensitivity reactions to heparin.…”

“…If a heparin-induced skin lesion is observed, we recommend obtaining a punch biopsy, comparing platelet counts before, during and after therapy, and performing appropriate laboratory investigations to exclude heparininduced thrombocytopenia. If heparin-induced thrombocytopenia is excluded, either unfractionated heparin administered intravenously 6 or fondaparinux administered subcutaneously 20,23,24 can be used for further anticoagulation. If heparininduced thrombocytopenia is clinically suspected and alternative anticoagulation is required, argatroban, danaparoid or lepirudin can be used until heparin-induced thrombocytopenia is excluded.…”

“…The incidence of heparin-induced skin lesions is unknown, despite being increasingly reported. [2][3][4] Heparininduced skin lesions may be caused by at least 5 mechanisms: delayed-type (type IV) hypersensitivity responses, 2,[4][5][6] immune-mediated thrombocytopenia, 3 type I allergic reactions, 7,8 skin necrosis 9 and pustulosis. 10 Heparin-induced skin lesions may indicate the presence of life-threatening heparin-induced thrombocytopenia 11 -even in the absence of thrombocytopenia.…”

Heparin and low-molecular-weight heparin

“…Skin necrosis occurred distant from the injection site, and heparin-induced antibodies occurred in a majority of patients, although severe thrombocytopenia was only found in four cases; other pathogenic mechanisms as well as that causing HIT may be involved. Milder skin reactions classified as delayed hypersensitivity are relatively common with subcutaneous administration of UFH, but do not usually occur when UFH is given intravenously (128). Patients with skin lesions induced by UFH or LMWH are usually switched to alternative anticoagulants such as thrombin inhibitors, although fondaparinux has recently been suggested as an alternative therapy for such patients (129).…”

Need for an increasing awareness for heparin-induced skin lesions

“…Furthermore, one of our patients with HIHS was also diagnosed with immune-mediated HIT, indicating that HIHS does not rule out HIT. As therapeutic options for HIT and HIHS are diametrically opposed -for example, intravenous heparin administration is a safe therapeutic option in HIHS [13], but is contraindicated in HIT -rapid and valid diagnosis of heparin-induced skin lesions is essential for patient management. Therefore, in each patient with heparin-induced skin lesions, the underlying cause has to be defined by the appropriate investigations.…”