Heparin-induced thrombocytopenia (HIT). A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004.
Clinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed. Treatment in 1,291 episodes was for current HIT. Thromboembolism due to HIT was present in 39.4%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder, and 351 major operations were performed. Clinical outcomes were assessed during danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the danaparoid-treated patients 83.8% survived; 63.7% had no or minor adverse events and 20.1% suffered serious non-fatal adverse events. New thromboses occurred during 9.7% of treatment episodes, and 16.4% of treatment episodes had an inadequate treatment response (i. e. developed one or more of the following: new/extended thrombosis, persistent/new platelet count reduction, unplanned amputation during treatment and follow-up). Major bleeding was reported in 8.1% of treatment episodes. Clinical cross-reactivity of danaparoid (new/persistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event, i.e. a total of 45 patients (3.2%). Clinical outcomes of these case reports of patients given danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors, especially when a sufficient danaparoid dosing intensity was used in patients with isolated HIT. Post-operative bleeding limits danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.
Magnani
Harry N
HN
NV Organon, Oss, The Netherlands. harry.magnani@hetnet.nl
Gallus
Alex
A
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003429:Cross Reactions; D003871:Dermatan Sulfate / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005076:Exanthema / Q000209:etiology; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006497:Heparan Sulfate / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000209:etiology; D017410:Practice Guidelines as Topic; D013921:Thrombocytopenia / Q000209:etiology*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005343:Fibrinolytic Agents; D006493:Heparin; D006497:Heparan Sulfate; C035838:danaparoid