Efficacy and safety of recombinant activated factor VII in Glanzmann thrombasthenia: A systematic literature review

Background: Platelet transfusion is considered the standard treatment for preventing or controlling severe haemorrhage in Glanzmann thrombasthenia (GT). However, platelet transfusion can have detrimental effects, including the production of anti-GPIIb/IIIa isoantibodies or anti-HLA antibodies (Ab) and platelet transfusion refractoriness. Recombinant activated factor VII (rFVIIa) has been proposed as an alternative treatment to platelet transfusion.

Methods: We analyzed data from 77 case reports including 100 subjects to investigate the effectiveness and safety of rFVIIa in combination with platelets or antifibrinolytics for preventing or treating non-surgical bleeds, as well as surgical and obstetrical procedures in GT.

Results: The dosage of rFVIIa was consistent with previous recommendations (90 µg/kg per infusion). In subjects without Ab/refractoriness (n = 56), rFVIIa was effective in managing 93% of non-surgical bleeds (n = 42), 91% of minor (n = 11) and 92% of major (n = 26) surgical procedures and 89% of obstetrical procedures (n = 9). In subjects with Ab/refractoriness (n = 44), rFVIIa was effective in managing 90% of non-surgical bleeds (n = 39), and 75% of minor (n = 12) and 100% of major (n = 17) surgical procedures. The use of rFVIIa was safe, with 4 (2.7%) serious adverse events associated with rFVIIa.

Conclusion: Although the use of rFVIIa is currently restricted to subjects with Ab/refractoriness or when platelets are not available, our findings suggest expanding the indications for rFVIIa to encompass GT without Ab/refractoriness. Frontline use of rFVIIa may be proposed when clinically possible to mitigate the risks associated with platelet transfusion.