Adverse skin reactions to low molecular weight heparins: frequency, management and prevention

Adverse skin reactions to low molecular weight heparins (LMWH) are rare even though their true incidence is probably underestimated because of under-reporting. These reactions may occur as an urticarial rash, presumably due to local histamine release or have the features of a classic type I immediate hypersensitivity reaction. They can also present as skin necrosis often due to vasculitis (type III Arthus reaction) or heparin-induced thrombocytopenia. Erythematous, well circumscribed lesions without necrosis are usually secondary to a delayed type IV hypersensitivity reaction. Although most LMWH-induced skin lesions are benign, treatment should be discontinued. In type I reactions or in the presence of skin necrosis with or without heparin-induced thrombocytopenia, the LMWH should be replaced by an alternative medication such as danaparoid sodium or hirudin. Platelet counts should be monitored to diagnose heparin-induced thrombocytopenia. In a type IV delayed hypersensitivity reaction, in the absence of severe, extensive, life-threatening mucocutaneous manifestations, a first-line pragmatic approach consists, in our view, of replacing the particular LMWH with another one. If the skin symptoms do not improve, cutaneous tests may help detect the presence of a cross-reactivity between the available preparations of LMWHs and danaparoid sodium. In the presence of a negative subcutaneous provocation test, the compound can be used with little risk. If all types of LMWH and danaparoid sodium are positive in skin testing, mechanical prevention or oral anticoagulants should be used, and intravenous injections of any kind of heparin should be avoided because of the potential risk of anaphylactic shock. Alternatively, hirudin might be administered but experience with this compound is still very limited. Prevention is only possible in type IV hypersensitivity skin reactions, by avoiding long term LMWH therapy, particularly in middle-aged, obese women and during pregnancy. In these patients, oral anticoagulation should be preferred, whenever possible. In conclusion, though rare, skin reactions to LMWH may have important consequences which can be reduced by rapid diagnosis and appropriate management.