Treatment of Venous and Arterial Thromboembolism

Patients with HIT frequently have one or more acute thromboses, which may have occurred before the development of HIT, as a complication of HIT itself, or both (Warkentin and Kelton, 1996). Venous thrombosis complicates HIT more often than does arterial occlusion. Indeed, in the compassionate-use program, the ratio of venous to arterial thrombosis was 2: 1 (Ortel and Chong, 1998). Even without thrombosis, HIT patients require continuation of antithrombotic therapy after heparin cessation (Warkentin and Greinacher, 2004). Currently, danaparoid, lepir-udin, and argatroban are believed to be effective in this situation (Warkentin et al., 1998). These agents have in common the capacity to inhibit thrombin directly (lepirudin, argatroban) or its generation (danaparoid).

Initially in the compassionate-use program, it was recommended that HIT patients with acute thrombosis receive iv danaparoid administered as a bolus of 2500 U, followed by an infusion of danaparoid at 400 U/h for 4 h, followed by 300 U/h for 4 h, and then 150-200 U/h for at least 5 days, aiming for a plasma anti-Xa level of 0.5-0.8 anti-Xa U/mL. Table 1 describes the current protocol that takes into account the current amount of danaparoid per marketed ampule (750 anti-Xa U/ampule), as well as certain initial bolus dose adjustments based on body weight. Danaparoid is also effective when administered sc (de Valk et al., 1995); in this situation, the equivalent 24-h actual or estimated iv dose is given in two to three divided doses by sc injection over a 24-h period. For example, 2250 U (three ampules) every 12 h by sc injection is approximately equal to 190 U/h by iv infusion given over 24 h. In the compassionate-use program, 464 patients with acute thromboembolism were treated with danaparoid, with efficacy judged to be over 90% (Ortel and Chong, 1998).

Danaparoid also proved efficacious for HIT-associated thrombosis in a prospective, randomized, controlled study (Chong et al., 2001). HIT patients with an acute thrombosis (venous, arterial, or both) were randomized to receive either danaparoid plus warfarin or dextran 70 plus warfarin. Dextran 70 is a glucose polymer with an average molecular mass of 70,000 Da. It is a weak antithrombotic

TABLE 1 Danaparoid Dosing Schedules in HIT Patients

Clinical indication

Danaparoid dosing schedule

Prophylaxis of VTE

Treatment of VTE or arterial thromboembolism

Embolectomy or other peripheral vascular surgery

Intermittent hemodialysis (on alternate days)

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