Efficacy and safety of recombinant activated factor VII for secondary prophylaxis in patients with Glanzmann thrombasthenia

Abstract

BACKGROUND: Glanzmann thrombasthenia (GT) is a rare inherited platelet disorder associated with recurrent and sometimes life-threatening bleeding. Recombinant activated factor VII (rFVIIa) is approved for treatment of bleeding episodes or surgical prophylaxis in patients with GT who are refractory or alloimmunized to platelet transfusions. However, evidence for its use as secondary prophylaxis remains scarce. OBJECTIVES: This study described the efficacy and safety of rFVIIa secondary prophylaxis in patients with GT and recurrent and uncontrolled bleeding despite standard therapy. METHODS: A multicenter, retrospective study of patients with GT included in the Spanish Registry of Patients with Inherited Platelet Disorders (RETPLAC) was performed. We evaluated bleeding severity using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT) and calculated the annualized bleeding rate (ABR) before and during rFVIIa prophylaxis. RESULTS: Of the 37 patients with GT included in RETPLAC, 4 patients received regular rFVIIa prophylaxis due to recurrent severe bleeding. Median baseline ISTH-BAT score was 13.5 (IQR, 9.5-18), and median preprophylaxis ABR was 3 (IQR, 3-5.25). All patients received rFVIIa of 90 ?g/kg, 3 twice weekly and 1 monthly. The median prophylaxis duration was 7.5 months (IQR, 6.75-12). Prophylaxis led to a 57.1% overall reduction in ABR, with resolution of severe bleeding in 2 patients and reduction in frequency in the remaining 2. Three patients achieved transfusion independence. All patients showed improvement in hemoglobin and iron profile. No thrombotic or adverse events occurred. CONCLUSION: Secondary prophylaxis with rFVIIa may be an effective option in patients with GT and recurrent severe bleeding unresponsive to standard therapy. Prospective studies are necessary to optimize dosing schedules and define its role in secondary prophylaxis.