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Published on: February 28, 2012
Special considerations with fondaparinux therapy: heparin-induced thrombocytopenia and wound healing
William E Dager1, Judith Andersen, Edith Nutescu
1Department of Pharmacy, University of California-Davis Medical Center, and University of California-Davis School of Medicine, Sacramento, California, USA.
Multiple options for anticoagulation therapy are now available, placing an additional responsibility on health care workers for choosing the optimal therapy for each patient. The heparins carry a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated reaction to heparin that may lead to pulmonary embolism and death. Fondaparinux, a new, synthetic pentasaccharide, binds to antithrombin III and potentiates antithrombin III's inhibition of factor Xa. Fondaparinux does not bind to platelet factor 4 and thus is theoretically unable to cause immunoallergic HIT. Unlike low-molecular-weight heparins, fondaparinux does not cross-react in vitro with sera from patients with clinical cases of HIT. These findings suggest that fondaparinux would not lead to formation of HIT antibodies and would not provoke clinical thrombosis in patients who had HIT antibodies because of previous exposure to heparins. To date, no cases of immunoallergic HIT have been associated with fondaparinux use in clinical trials. Anecdotal evidence suggests that fondaparinux eventually may prove to be valuable for preventing and treating thrombosis in patients with HIT. The effect of anticoagulants on wound healing is another consideration when choosing a thromboprophylactic strategy after major surgery. There is evidence that thrombin plays a role in wound healing, but fondaparinux is too small to enable antithrombin III to inhibit thrombin. Thus, fondaparinux may be less likely than a low-molecular-weight heparin to interfere with wound healing.
Multiple options for anticoagulation therapy are now available, placing an additional responsibility on health care workers for choosing the optimal therapy for each patient. The heparins carry a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated reaction to heparin that may lead to pulmonary embolism and death. Fondaparinux, a new, synthetic pentasaccharide, binds to antithrombin III and potentiates antithrombin III's inhibition of factor Xa. Fondaparinux does not bind to platelet factor 4 and thus is theoretically unable to cause immunoallergic HIT. Unlike low-molecular-weight heparins, fondaparinux does not cross-react in vitro with sera from patients with clinical cases of HIT. These findings suggest that fondaparinux would not lead to formation of HIT antibodies and would not provoke clinical thrombosis in patients who had HIT antibodies because of previous exposure to heparins. To date, no cases of immunoallergic HIT have been associated with fondaparinux use in clinical trials. Anecdotal evidence suggests that fondaparinux eventually may prove to be valuable for preventing and treating thrombosis in patients with HIT. The effect of anticoagulants on wound healing is another consideration when choosing a thromboprophylactic strategy after major surgery. There is evidence that thrombin plays a role in wound healing, but fondaparinux is too small to enable antithrombin III to inhibit thrombin. Thus, fondaparinux may be less likely than a low-molecular-weight heparin to interfere with wound healing.
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