Clinical Use of Danaparoid in Patients with HIT

Danaparoid has been used extensively to treat patients with HIT (Chong and Magnani, 1992; Magnani, 1993, 1997; Magnani and Gallus, 2006). After the diagnosis of HIT and discontinuation of heparin administration, patients often require an alternative anticoagulant for any one of the following indications: (1) treatment of a recent or new thrombosis; (2) prophylaxis of venous thromboembolism; (3) anticoagulation for cardiopulmonary bypass (CPB) surgery or peripheral arterial surgery; (4) anticoagulation for intermittent or continuous hemodialysis or continuous renal replacement therapy (CRRT); (5) cardiac catheterization or coronary angioplasty; or (6) maintenance of intravascular catheter patency. The rationale for the use of danaparoid in these various situations includes: its non-heparin structure, its low degree of cross-reactivity with HIT antibodies compared with LMWH (Makhoul et al., 1986; Chong et al., 1989; Greinacher et al., 1992; Kikta et al., 1993; Vun et al., 1996), its ability to inhibit HIT antibody-induced platelet activation (Chong et al., 1989), and its overall favorable efficacy and safety profile.

The largest clinical experience with the use of danaparoid in the treatment of patients with HIT is in the compassionate-use (named patient) program organized by the manufacturer (Magnani, 1993, 1997). From 1981 to 1997, over 750 patients were treated under this program for the various indications listed earlier (Ortel and Chong, 1998). The duration of treatment ranged from 1 day to 3.5 yr, and the post-treatment follow-up was 3 mo. Interim, updated reports of this program have been published (Chong and Magnani, 1992; Magnani, 1993, 1997). The overall success rate, defined as platelet count recovery without new, progressive, or recurrent thrombosis during the danaparoid treatment period, or thrombotic death during 3 mo follow-up, and the absence of any adverse effect necessitating treatment cessation, has been over 90%, as judged by the local physician-investigators. However, as this definition does not include non-thrombotic death, the overall mortality observed in the program was 18%, including deaths during the post-treatment follow-up. Most patients in this program received danaparoid for the treatment of acute thromboembolism, often in the setting of severe illness such as renal or multisystem organ failure.

Besides this compassionate-use program, other studies supporting the efficacy of danaparoid therapy for acute HIT include a randomized controlled trial comparing danaparoid with dextran (Chong et al., 2001), a retrospective analysis comparing danaparoid with lepirudin (Farner et al., 2001), and a historically controlled retrospective cohort study that compared danaparoid with ancrod (Lubenow et al., 2006).

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