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

INTRODUCTION:

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: Norbert Lubenow, Theodore E Warkentin, Andreas Greinacher, Antje Wessel, Debi-Ann Sloane, Erica L Krahn, Harry N Magnani
• Journal: Thrombosis research (Thromb Res) Vol. 117 Issue 5 Pg. 507-15 ( 2006) ISSN: 0049-3848 [Print] United States
• PMID: 15907979 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coumarins
• Dermatan Sulfate
• Heparin
• Chondroitin Sulfates
• Heparitin Sulfate
• coumarin
• danaparoid
• Ancrod

Topics

• Aged
• Ancrod (administration & dosage, therapeutic use)
• Canada
• Chondroitin Sulfates (administration & dosage, therapeutic use)
• Cohort Studies
• Coumarins (administration & dosage, therapeutic use)
• Dermatan Sulfate (administration & dosage, therapeutic use)
• Female
• Germany
• Heparin (adverse effects)
• Heparitin Sulfate (administration & dosage, therapeutic use)
• Humans
• Male
• Outcome Assessment, Health Care
• Platelet Count
• Practice Patterns, Physicians' (trends)
• Retrospective Studies
• Survival Analysis
• Thrombocytopenia (chemically induced, drug therapy)