PB1055 - Retention of critical hemostatic functions of amotosalen-UVA Pathogen-Reduced Cryoprecipitated Fibrinogen Complex under variable shear flow rates

Background: Cryoprecipitate anti-haemophilic factor derived from frozen plasma (CRYO-AHF) is enriched for fibrinogen (FIB), vWF, FVIII and fibronectin to treat hemorrhage. CRYO-AHF has a 4-6 hour post-thaw expiration due to risk of transfusion-transmitted infection (TTI). Short post thaw expiration limits availability for transfusion. Amotosalen-UVA pathogen reduction treatment (A-PRT: INTERCEPT Blood System, Cerus) is FDA approved to reduce TTI risk for manufacture of Cryoprecipitated Fibrinogen Complex (IFC) with 5-day post thaw expiration, increasing availability for early treatment of hemorrhage with reduced wastage.

Aims: To evaluate critical hemostatic functions of adhesive proteins in IFC and lyophilized IFC (LIFC).

Methods: CRYO-AHF, IFC, LIFC and commercial fibrinogen concentrate (CFC) were evaluated for support of platelet adhesion and aggregation using various shear rates (300 – 1,500 – 3000 s-1) with various FIB substrates in microfluidic and aggregometry assays.

Results: We observed no differences in the kinetics of platelet adhesion to immobilized CRYO-AHF, IFC and LIFC, under low shear flow (300 s-1). In contrast, a lower number of platelets adhered onto immobilized CFC at low shear due to absence of functional vWF. The central importance of IIb3/fibrinogen and GPIb-IX-V/vWF bonds in platelet interactions with CRYO-AHF, IFC, LIFC was confirmed by inhibition with abciximab and caplacizumab, respectively. Born platelet aggregometry confirmed all FIB sources promoted efficient platelet aggregation. Perfusion of reconstituted plasma-free blood (RBC + platelets + IFC or LIFC) on immobilized vWF-binding peptide (1,500 s-1) showed a slight reduction of platelet adhesion only for LIFC compared to IFC and CRYO-AHF. Finally, perfusion of reconstituted blood on collagen (3,000 s-1) indicated that CRYO-AHF, IFC and LIFC formed thrombi to similar levels.

Conclusion(s): IFC and LIFC prepared with A-PRT retained critical hemostatic functions of vWF and FIB to support platelet adhesion and aggregation under physiologic shear rates. IFC is a therapeutic option for early treatment of patients with massive hemorrhage.