Results of a systematic evaluation of treatment outcomes for heparin-induced thrombocytopenia in patients receiving danaparoid, ancrod, and/or coumarin explain the rapid shift in clinical practice during the 1990s

IntroductionRandomized controlled trials evaluating treatment of acute, transient, but uncommon diseases are difficult to perform. The prothrombotic adverse drug reaction, heparin-induced thrombocytopenia (HIT), is such an example. During the mid-1980s, the defibrinogenating snake venom, ancrod (± warfarin, Canada), or coumarin (warfarin, Canada; phenprocoumon, Germany) alone, were often used to treat HIT. During the 1990s, danaparoid ± coumarin began to replace ancrod (± coumarin), or coumarin alone, for treating HIT, despite danaparoid not being approved for treatment of HIT.MethodsWe performed a retrospective evaluation of treatment outcomes from 1986 to 1999, comparing danaparoid ± coumarin (n = 62) versus ancrod ± coumarin or coumarin alone (controls, n = 56).ResultsThe predefined composite endpoint of adjudicated new, progressive, or recurrent thrombosis (including thrombotic death), or limb amputation, at day 7 (maximum, one event per patient) was significantly lower in danaparoid-treated patients, compared with controls: 8/62 = 12.9% (95% CI, 4.3–21.5) vs. 22/56 = 39.3% (95% CI, 26.1–52.5); p = 0.0014. We also found a lower frequency of the composite endpoint at end of study (day 35) in danaparoid-treated patients: 12/62 = 19.4% vs. 24/56 = 42.9% (p = 0.0088). Major bleeding (by day 7) occurred in 7/62 (11.3%) and 16/56 (28.6%) of danaparoid-treated and control patients, respectively (p = 0.0211).ConclusionsThe replacement of ancrod ± coumarin, or coumarin alone, by danaparoid (± coumarin) in the mid-1990s for the treatment of HIT was justified by improved efficacy and safety.