Pathogen-reduced plasma, cryoprecipitate reduced for therapeutic plasma exchange

Therapeutic plasma exchange (TPE) for thrombotic thrombocytopenic purpura (TTP) and auto-immune disorders involves repeated patient exposure to allogenic plasma with the risk of transfusion-transmitted infection (TTI). Amotosalen-UVA Pathogen Reduction technology is FDA approved to manufacture pathogen-reduced plasma, cryoprecipitate reduced (PRPCR), a form of cryoprecipitate poor plasma (CPP) with potentially improved TPE outcomes and reduced TTI risk.

PRPCR was manufactured from pathogen-reduced (PR) plasma. Thrombin generation, fibrinogen, Factors II, V, VII, VIII, IX, X, XI, XIII, VWF, ADAMTS13, Protein C, Protein S, α-2 plasmin inhibitor (α-2 PI), IgG, IgM, and IgA were measured. Microfluidic chamber assays at variable shear rates characterized PRPCR-mediated platelet adhesion and aggregation.

Compared to PR plasma, fibrinogen, Factor VIII, and VWF levels were depleted in PRPCR. Factors II, V, VII, IX, X, XI, XIII, thrombin generation, Protein C, Protein S, α-2 PI, ADAMTS13, and immunoglobulins were conserved. At low wall shear rates (300 s^-1) PRPCR supported platelet adhesion. Perfusion of plasma-free blood containing PRPCR flowed over immobilized VWF binding peptide (100 μg/mL) and showed absence of platelet adhesion. Perfusion of plasma-free blood containing PRPCR flowed over immobilized collagen (200 μg/mL) at high wall shear rate (1500 s^-1) and demonstrated no platelet thrombus formation.

PRPCR retained hemostatic capacity, anti-thrombotic proteins, and ADAMTS13, but collagen induced platelet aggregation was negligible at high shear due to depletion of functional high molecular weight VWF. PRPCR is a CPP option for TPE with reduced platelet-mediated thrombotic risk and TTI risk, but with retention of plasma hemostatic capacity and immunoglobulins.