Haemophilia | 2021
Characterization of a plasma‐derived double−viral‐inactivated factor VIII concentrate (antihaemophilic factor [human]): Focus on TTP treatment
Abstract
Dear Editor, We are writing to share our data on a plasma-derived double−viralinactivated factor VIII (FVIII) concentrate (Antihaemophilic factor [Human]) in an effort to help patients with thrombotic thrombocytopenic purpura (TTP), a rare form of thrombotic microangiopathy associated with microangiopathic haemolytic anaemia and multiorgan dysfunction, typically involving the brain, kidneys, heart and gastrointestinal tract.1,2 This condition is due to a deficiency of ADAMTS13, an enzyme responsible for the cleavage of ultra-large von Willebrand factor (VWF) multimers.1,3 In the absence of functional ADAMTS13, ultra-large VWF multimers can accumulate and interact with platelets to produce occlusive microvascular thrombosis.3 Thrombotic thrombocytopenic purpura can be congenital (hereditary) or mediated by an immune response (acquired) and can be fatal if not appropriately addressed.1,2 ADAMTS13 replacement with fresh frozen plasma (FFP) for on-demand or prophylactic treatment is the standard of care for patients with congenital TTP.4 Treatment of acquired TTP usually involves the infusion of FFP or exchange plasmapheresis in order to putatively remove anti-ADAMTS13 autoantibodies and replace functional ADAMTS13 in combination with corticosteroid therapy to suppress the immune response.2,5 In both congenital and acquired TTP, allergic reactions, including anaphylaxis, as well as development of overload complications of FFP, present a therapeutic limitation of FFP administration.4 We decided to investigate the potential of Koāte in the treatment of TTP, focusing on the characterization of ADAMTS13 and VWF contained in the concentrate, based on previous observations.6 Peyvandi and colleagues proposed that a FVIII concentrate (Antihaemophilic factor [Human]; Koāte®; Kedron Biopharma; Fort Lee, NJ), indicated for the treatment of classical haemophilia A, be considered as an alternative treatment for TTP. The use of Koāte represents potential advantages over the standard use of FFP as it would require much smaller volume infusions, avoiding volume overload, and would present a better pathogen safety profile due to the robust virucidal treatments incorporated in its manufacturing process.6 We characterized in vitro 12 lots of Koāte in terms of the following: