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

Abstract

Summary. Background: 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. Objectives: An international survey was conducted to evaluate further the efficacy and safety of rFVIIa in GT patients. 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. Results: 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 (≥ 80 µg kg−1 rFVIIa/injection, dosing interval ≤ 2.5 h, three or more doses before failure declaration) was used compared with other regimens (77%; 24/31 vs. 48%, 19/40; χ2, 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. Conclusion: rFVIIa seems a potential alternative to platelet transfusion in GT patients, particularly in those with antiplatelet antibodies and/or platelet refractoriness.

The international prospective Glanzmann Thrombasthenia Registry: treatment and outcomes in surgical intervention

“…This is similar to the regimen we previously suggested for bleeding episodes (rFVIIa ≥80 mg/kg at intervals of 2.5-h or less for three or more doses), 7 and is also similar to standard rFVIIa dosing in patients with congenital hemophilia A or B with inhibitors.…”

“…The GTR data reported here come from the largest observational study on GT patients and include information on the management of invasive procedures; the shortcomings of the previous survey 7 are addressed in that the use of hemostatic agents other than rFVIIa is now included.…”

“…2,[4][5][6] Previously, we showed that recombinant human factor VIIa (rFVIIa) was a good alternative therapeutic agent for bleeding and surgical prophylaxis in GT. 7,8 Data from a previous international survey of 59 patients treated for 108 bleeding episodes and 34 surgical/invasive procedures 7 allowed a preliminary suggestion for a more optimal rFVIIa regimen (rFVIIa ≥80 mg/kg given at ≤2.5-h intervals for three or more doses) for the treatment of moderate/severe bleeding episodes. However, the number of evaluable surgical procedures was too small for an appropriate regimen for surgical prophylaxis to be proposed.…”

Clinical utility gene card for: Glanzmann thrombasthenia

“…Activated recombinant factor VII (rFVIIa) provides an alternative treatment for GT patients who develop such antibodies. 19 Patients with mutations causing absence or premature termination of aIIb or b3 are particularly prone to form antibodies against aIIbb3. 20 This finding may help in deciding whether platelet transfusion or rFVIIa should be used.…”

Glanzmann’s Thrombasthenia: A Rare Cause of Recurrent Profuse Epistaxis

“…Recently, successful use of recombinant factor VIIa (NovoSevenÒ; Novo Nordisk A/S, Malov, Denmark) offers an alternative approach to early hemostasis, especially for patients with antibodies and/or a history of refractoriness to transfusion [14]. Other treatment modalities include desmopressin (DDAVP) http://www.frca.co.…”