Unfractionated heparin compared with low-molecular-weight heparin as related to heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is a severe side effect of treatment with unfractionated heparin. The relation of low-molecular-weight heparin to heparin-induced thrombocytopenia is less well understood. This review will summarize what is known about the similarities and differences between thrombocytopenia induced by low-molecular-weight heparin and that induced by unfractionated heparin.

The pathophysiology of unfractionated heparin-induced thrombocytopenia, caused by the development of antibodies to heparin/platelet factor 4 complexes, holds true for low-molecular-weight heparin because the molecules of the latter are of the same saccharidic structure as those of unfractionated heparin. Owing to their smaller size, however, low-molecular-weight heparin does not interact with platelet factor 4 and platelets as efficiently as does unfractionated heparin. This translates to a two- to threefold lower risk of immune sensitization (antibody generation and occurrence of clinical heparin-induced thrombocytopenia). Low-molecular-weight heparin-induced thrombocytopenia antibodies are more often immunoglobulin A and immunoglobulin M, in contrast to the immunoglobulin G antibodies generated with unfractionated heparin-induced thrombocytopenia, which tend to be more often associated with clinical heparin-induced thrombocytopenia. The clinical expression of low-molecular-weight heparin-induced thrombocytopenia is generally similar to that of unfractionated heparin-induced thrombocytopenia but can have a slower onset, more severe thrombocytopenia, and slower platelet count recovery. Given that low-molecular-weight heparin, of itself, is linked with heparin-induced thrombocytopenia pathophysiology and it can interact with most preexisting heparin-induced thrombocytopenia antibodies generated after exposure to unfractionated heparin, treatment of heparin-induced thrombocytopenia patients with low-molecular-weight heparin is contraindicated.

The risk of the development of heparin-induced thrombocytopenia with low-molecular-weight heparin treatment is reduced relative to the frequency of unfractionated heparin-induced thrombocytopenia, but it is not eliminated, and platelet counts should be monitored with treatment.