Prophylaxis During Acute HIT

In contrast to the comparable efficacy of danaparoid and lepirudin when used in therapeutic doses to treat HIT-associated thrombosis (discussed previously), lepirudin appeared somewhat more effective than danaparoid when prophylactic-dose regimens were compared for preventing the single endpoint of new thrombosis (91.4% vs. 81.4%; p = 0.138); this difference was larger, and reached statistical significance, when the composite endpoint (new thrombosis, limb amputation, or death) was examined (Fig. 2a). However, superior efficacy of lepirudin came at a price: for patients without thrombosis at baseline (most of whom thus received prophylactic-dose therapy), lepirudin was associated with a trend to more major bleeding events than danaparoid (16.3% vs. 2.9%; p = 0.075) (Farner et al., 2001). Kodityal and colleagues (2003) also reported five patients who developed new thromboses while receiving relatively low doses of danaparoid (usually, 1250 U every 12 h by sc injection).

These data, and other observations describing early new thrombotic events in patients on prophylactic-dose danaparoid and which respond favorably to increases in danaparoid dosing intensity (Lindhoff-Last et al., 2005; Magnani and

Gallus, 2006), support the current treatment recommendation that therapeutic doses of danaparoid are appropriate for most patients with HIT, whether they have HIT-associated thrombosis or just isolated HIT (Warkentin, 2001; Warkentin and Greinacher, 2004) (see Chapters 1 and 12). A comparable situation exists with the two DTIs available to treat HIT: argatroban is approved in the United States in identical therapeutic-dose regimen both for HIT-associated thrombosis and isolated HIT (see Chapter 15) and although there exists a lower-dose (prophylactic) regimen for lepirudin to manage isolated HIT (see Chapter 14), the use of anticoagulant monitoring to adjust the infusion rate means that most patients eventually receive doses that approach the therapeutic regimen (Warkentin, 2001).

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