Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann's thrombasthenia: results of an international survey

Abstract

Antibodies to glycoprotein (GP) IIb-IIIa and/or HLA may render platelet transfusions ineffective to stop bleeding or to cover surgery in patients with Glanzmann's thrombasthenia (GT). Anecdotal reports suggest recombinant factor (rF)VIIa might be a therapeutic alternative in these situations. An international survey was conducted to evaluate further the efficacy and safety of rFVIIa in GT patients. We analyzed the use of rFVIIa during 34 surgical/invasive procedures and 108 bleeding episodes in 59 GT patients including 29 with current or previous antiplatelet antibodies, and 23 with a history of refractoriness to platelet transfusion. rFVIIa was effective in 29 of the 31 evaluable procedures, and in 77 of the 103 evaluable bleeding episodes of which eight had a recurrence. A significantly higher success rate was observed in severe bleeding episodes when an arbitrarily defined 'optimal regimen' derived from the Canadian pilot study results (> or = 80 micro g kg(-1) rFVIIa/injection, dosing interval < or = 2.5 h, three or more doses before failure declaration) was used compared with other regimens (77%; 24/31 vs. 48%, 19/40; chi(2), P = 0.010). Patients given maintenance doses had significantly fewer recurrences within 48 h of bleed cessation compared with those not given any (Fisher's exact test, P = 0.022). One thromboembolic event and one blood clot in the ureter occurring in surgical patients following prolonged continuous infusion of high-dose rFVIIa and antifibrinolytic drug use have been previously reported. rFVIIa seems a potential alternative to platelet transfusion in GT patients, particularly in those with antiplatelet antibodies and/or platelet refractoriness.