Danaparoid Cross Reactivity

Danaparoid is a mixture of non-heparin anticoagulant glycosaminoglycans, predominantly (low-sulfated) heparan sulfate, dermatan sulfate, and chondroitin sulfate (see Chapter 13). About 10-40% of HIT patient sera "cross-react" in vitro with danaparoid, depending on the assay used (lower cross-reactivity rates by platelet aggregometry, higher rates with fluid-phase PF4/heparin immunoassays) (Vun et al., 1996; Warkentin et al., 2005; Magnani and Gallus, 2006). The question arises as to the in vivo relevance (if any) of this phenomenon. In our experience, the majority of patients with detectable in vitro cross-reactivity have favorable clinical courses that do not differ significantly (either in clinical outcomes or in time to platelet count recovery) from patients without cross-reactivity (Warkentin, 1996). Furthermore, it is not possible to distinguish in vivo cross-reactivity from a severe natural history of HIT. For example, the authors are aware of HIT patients with strong antibodies, whose thrombocytopenia persisted for several weeks despite cessation of all heparin and during treatment with a DTI; had such a patient received danaparoid, the physicians inevitably would have judged the patient to have had in vivo cross-reactivity. Furthermore, in many patients, therapeutic concentrations of danaparoid disrupt PF4/heparin/IgG immune complexes, thereby inhibiting HIT antibody-induced platelet activation (Chong et al., 1989); this is a unique pharmacologic attribute not shared by any other anticoagulant. For all of these reasons, we do not advise testing for in vitro cross-reactivity in patients in whom danaparoid treatment is planned.

Recommendation. In vitro cross-reactivity testing for danaparoid using HIT patient serum or plasma is not recommended prior to danaparoid administration (grade 1C).

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