Decreased Prevalence of Heparin-Induced Thrombocytopenia with Low-Molecular-Weight Heparin and Related Drugs

Heparin-induced thrombocytopenia (HIT) Type II represents a disease spectrum associated with a high risk of thrombosis leading to limb loss and death. The pathophysiology of HIT is based on the development of antibodies to the heparin-platelet factor 4 (PF4) complex. Unfractionated heparin (UFH) is heterogeneous in molecular chain length and degree of sulfation accounting in part, for, the heterogeneity of HIT antibodies. Because of its smaller size, low-molecular-weight heparin (LMWH) does not interact with PF4 and platelets as efficiently as does UFH. This translates into a lower risk of immune sensitization with LMWH than with UFH treatment. LMWH is less likely than UFH to cause antibody generation and thus patients do not develop clinical HIT at the same frequency with LMWH as with UFH treatment. The antibodies generated by LMWH treatment are more often immunoglobulin A (IgA) and IgM as opposed to IgG antibodies, which are associated with symptomatic clinical HIT generated by exposure to UFH. However, platelet activation/aggregation can occur from LMWHs in the presence of most pre-existing HIT antibodies that had been generated from UFH exposure, although the response is less than that caused by UFH plus HIT antibody. With the expanded use of LMWH, the frequency of clinical HIT may naturally decline, given that LMWHs are less likely to generate HIT antibody.

KEYWORDS

Heparin-induced thrombocytopenia - low-molecular-weight heparin - unfractionated heparin - antibody - platelets

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