Retention of critical platelet hemostatic functions of amotosalen‐ UVA pathogen‐reduced cryoprecipitated fibrinogen complex

Abstract Background Cryoprecipitate Anti‐Haemophilic Factor ( CRYO ‐ AHF ) is enriched for fibrinogen, VWF , FVIII , FXIII and fibronectin, but has short post‐thaw expiration due to risk of transfusion‐transmitted infection ( TTI ) limiting availability for rapid treatment. Amotosalen‐ UVA pathogen reduction treatment (A‐ PRT ) to manufacture pathogen‐reduced cryoprecipitated fibrinogen complex ( PRCFC ) allows 5‐day post‐thaw expiration, reduces TTI risk, and facilitates early treatment of hemorrhage. Aims To evaluate adhesive protein functions in PRCFC and lyophilized PRCFC ( LIFC ). Methods CRYO ‐ AHF , PRCFC , LIFC , and commercial fibrinogen concentrate ( CFC ) were evaluated for platelet adhesion and aggregation in variable shear microfluidic assays. Results Platelet adhesion kinetics to CRYO ‐ AHF , PRCFC, and LIFC , under low shear flow (300 s −1 ) were conserved. Platelet adhesion to CFC at low shear was reduced due to absence of functional VWF . αIIbβ3 integrin/fibrinogen and GPIb ‐ IX ‐V/ VWF platelet interactions with CRYO ‐ AHF , PRCFC , and LIFC were confirmed by abciximab and caplacizumab inhibition, respectively. All fibrinogen sources promoted efficient platelet aggregation. Perfusion of reconstituted plasma‐free blood ( RBC + platelets + various cryoprecipitates) on immobilized VWF ‐binding peptide (1500 s −1 ) showed impaired platelet adhesion to CFC compared to PRCFC and CRYO ‐ AHF . Perfusion of reconstituted blood on collagen (3000 s −1 ) indicated CRYO ‐ AHF , PRCFC and LIFC formed thrombi to similar levels. Platelets treated with A‐ PRT combined with PRCFC or LIFC retained similar activity to CRYO ‐ AHF for platelet aggregation and thrombus formation on collagen. Conclusions PRCFC and LIFC retained critical hemostatic functions of VWF and fibrinogen to support platelet adhesion and aggregation during physiologic shear. PRCFC and LIFC represent a therapeutic option for early treatment of massive hemorrhage.