Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.
OBJECTIVE
To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis.


METHODS
Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital.


RESULTS
With danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6-71.4; p = 0.02). Clinical recovery with danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2-16.7; p = 0.03). Overall clinical effectiveness of danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment.


CONCLUSIONS
danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.
Chong
B H
BH
Prince of Wales, Sydney, Australia.
Gallus
A S
AS
Cade
J F
JF
Magnani
H
H
Manoharan
A
A
Oldmeadow
M
M
Arthur
C
C
Rickard
K
K
Gallo
J
J
Lloyd
J
J
Seshadri
P
P
Chesterman
C N
CN
D000368:Aged; D002809:Chondroitin Sulfates / Q000008:administration & dosage* / Q000633:toxicity; D003871:Dermatan Sulfate / Q000008:administration & dosage* / Q000633:toxicity; D003911:Dextrans / Q000008:administration & dosage* / Q000633:toxicity; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000276:immunology; D006497:Heparan Sulfate / Q000008:administration & dosage* / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D013810:Therapeutic Equivalency; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D003911:Dextrans; D004338:Drug Combinations; D006493:Heparin; D006497:Heparan Sulfate; D014859:Warfarin; C035838:danaparoid