title: 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.
abstract: BACKGROUND
  Randomized 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.
  
  
  METHODS
  We 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).
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Lubenow
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.forename: Antje
authors.initials: A
authors.lastname: Wessel
authors.forename: Debi-Ann
authors.initials: DA
authors.lastname: Sloane
authors.forename: Erica L
authors.initials: EL
authors.lastname: Krahn
authors.forename: Harry N
authors.initials: HN
authors.lastname: Magnani
mesh_terms: D000368:Aged; D000721:Ancrod / Q000008:administration & dosage / Q000627:therapeutic use*; D002170:Canada; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D003374:Coumarins / Q000008:administration & dosage / Q000627:therapeutic use*; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D006493:Heparin / Q000009:adverse effects*; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D010976:Platelet Count; D010818:Practice Patterns, Physicians' / Q000639:trends; D012189:Retrospective Studies; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000721:Ancrod; D002809:Chondroitin Sulfates; D003374:Coumarins; D003871:Dermatan Sulfate; D006493:Heparin; D006497:Heparan Sulfate; C030123:coumarin; C035838:danaparoid