Delayed-type hypersensitivity and cross-reactivity to heparins and danaparoid: a prospective study.
BACKGROUND
Delayed-type hypersensitivity (DTH) reactions in patients receiving heparin may occur with both unfractionated (UFHs) and low molecular weight heparins (LMWHs). Skin testing is a clue to detect tolerated heparin or heparinoid preparations for further treatment.


OBJECTIVE
To study in vivo cross-reactivity between LMWHs, UFHs, and danaparoid by skin testing in patients with suspected DTH to heparin.


METHODS
Patients who fulfilled the criteria for the diagnosis of suspected heparin allergy were involved in a prospective study after informed consent. Patients presented with or had a history of typical erythematous plaques at the heparin injection sites. Skin testing was performed by subcutaneous injections of heparin (300-500 IU anti-Xa activity) and danaparoid (375 IU, eight patients). Desirudin (27,000 IU) was tested in three patients. We read skin reactions after 24, 48, and 96 hours and after 7 days.


RESULTS
Fourteen female and 4 male patients were included in our series. Erythematous plaques had been reported or developed after 14-35 days in patients during first-time heparin treatment and after 2-10 days in reexposed patients. Positive skin test results were seen in 15 of 18 (83.3%) patients. Of these, 11 (73.3%) showed cross-reactivity between heparins and/or danaparoid. Six patients reacted to LMWHs only, nine patients to both LMWHs and UFHs. Danaparoid was tolerated in six of eight patients; desirudin was tolerated in all three patients tested.


CONCLUSIONS
DTH to heparins is characterized by considerable cross-reactivity between LMWHs, UFHs, and danaparoid. UFHs may be tolerated even if LMWHs are not. Subcutaneous testing of a panel of heparins, danaparoid, and desirudin (hirudin) is recommended to determine acceptable treatment options for patients allergic to specific heparins.
Department of Dermatology and Venereology, University of Innsbruck, Innsbruck, Austria.
A
A
Grassegger
P
P
Fritsch
N
N
Reider
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000276:immunology*; D002809:Chondroitin Sulfates / Q000276:immunology*; D003429:Cross Reactions; D003871:Dermatan Sulfate / Q000276:immunology*; D004338:Drug Combinations; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D005260:Female; D006493:Heparin / Q000276:immunology*; D006496:Heparinoids / Q000276:immunology*; D006497:Heparan Sulfate / Q000276:immunology*; D006629:Hirudins / Q000031:analogs & derivatives* / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000276:immunology; D012882:Skin Tests
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004338:Drug Combinations; D006493:Heparin; D006496:Heparinoids; D006497:Heparan Sulfate; D006629:Hirudins; D011994:Recombinant Proteins; C035838:danaparoid; C060225:desirudin