Adverse effects of heparin.

All the adverse effects of heparins are related to their wide variety of biological activities, with bleeding being the most important safety issue, resulting directly from the potency of heparin as an anticoagulant. However, it is hard to define the bleeding risk, since it depends on numerous parameters including the indication, dosage, method, and duration of heparin application, the clinical study design and definition of bleeding as well as patient characteristics and determinants of bleeding such as type of surgery and co-medication. Nonbleeding complications of heparins are caused by binding of heparin molecules to proteins other than antithrombin and to cells, which is generally more pronounced with unfractionated heparin than with low-molecular-weight heparins. Accordingly, heparin-induced thrombocytopenia, the most severe nonbleeding adverse reaction, occurs about 10 times less with low-molecular-weight heparins than with unfractionated heparin. Frequent and therefore important adverse reactions of heparins are skin lesions resulting from delayed-type hypersensitivity reactions. All the other undesirable effects are discussed as well, but they are mostly clinically irrelevant.