Pharmacology

Danaparoid exerts its antithrombotic effects predominantly by indirect inhibition of factor Xa; it has only minimal anti-factor IIa (antithrombin) activity. Hence,

(LMW) Heparin Danaparoid

FIGURE 1 Comparison of predominant disaccharide structure of heparin with danaparoid. The LMW heparin disaccharide is mostly (left) glucosamine-N-sulfate and (right) iduronic acid, whereas danaparoid's principal constituent, heparan sulfate, is predominantly (left) N-acetyl-glucosamine and (right) glucuronic acid. The degrees of sulfation (sulfate groups per disaccharide unit) for heparin and danaparoid are approximately 2.0-2.5 and 1.0-1.5, respectively (see Chapter 7). Abbreviation: LMW, low molecular weight.

(LMW) Heparin Danaparoid

FIGURE 1 Comparison of predominant disaccharide structure of heparin with danaparoid. The LMW heparin disaccharide is mostly (left) glucosamine-N-sulfate and (right) iduronic acid, whereas danaparoid's principal constituent, heparan sulfate, is predominantly (left) N-acetyl-glucosamine and (right) glucuronic acid. The degrees of sulfation (sulfate groups per disaccharide unit) for heparin and danaparoid are approximately 2.0-2.5 and 1.0-1.5, respectively (see Chapter 7). Abbreviation: LMW, low molecular weight.

the ratio of anti-factor Xa (anti-Xa) to antithrombin (anti-IIa) is > 22:1, which is considerably greater than that of LMWH preparations (2:1-4:1) and UFH (1:1) (Meuleman et al., 1982; Gordon et al., 1990; Meuleman, 1992). Its inhibition of factor Xa is mediated by AT and its minor inhibitory effect on thrombin by both AT and heparin cofactor II. Danaparoid also inhibits factor IX activation by IIa, thereby dampening a major feedback loop for thrombin generation (Ofosu, 1992). The predominant anticoagulant effect of danaparoid can be categorized as thrombin generation inhibition (TGI).

Danaparoid does not interfere with platelet function (Meuleman et al., 1982; Mikhailidis et al., 1984, 1987; Meuleman, 1987) and so, unlike UFH, it has minimal effect on formation of the platelet-dependent hemostatic plug (Meuleman, 1992). These characteristics of danaparoid contribute to its high therapeutic index (i.e., favorable benefit/risk ratio).

Danaparoid binds poorly to platelet factor 4 (PF4), the main heparin-binding protein responsible for HIT antibody induction, but it can interfere with the interaction between HIT antibodies and platelets (Chong et al., 1989).

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