Fresh-frozen plasma, pathogen-reduced single-donor plasma or bio-pharmaceutical plasma?

Abstract

Three types of therapeutic plasma are available that differ in their manufacturing processes, composition, clinical efficacy, and side effects. Quarantine-stored, not pathogen-reduced fresh-frozen plasma (QFFP) is prepared from single whole blood or plasma donations. The manufacture of pathogen-reduced single-donor plasmas such as methylene blue-light treated (MLP) or amotosalen-ultraviolet light treated plasma (ALP) involves the addition of a chemical followed by irradiation and subsequent removal of the chemical. Both plasma types show substantial fluctuation of clotting factor and inhibitor levels according to interindividual variations, and both carry the risk of inducing transfusion-associated lung injury (TRALI). Photo-oxidation in pathogen-reduced single-donor plasmas reduces clottable fibrinogen and other clotting factors markedly, and there is a lack of clear evidence showing whether this is harmful or not. MLP also appears to be less effective clinically than QFFP. Like clotting factor or inhibitor concentrates, solvent/detergent-treated plasmas (SDP) are bio-pharmaceutical preparations derived from large plasma pools, and variations in plasma protein levels from batch-to-batch are for that reason low. The SD manufacturing process inevitably involves a considerable reduction of plasmin inhibitor (PI), and moderate reduction of all other clotting factors and inhibitors in the final plasma bags. Clinical studies and broad clinical use have however shown that this does not significantly reduce clinical efficacy or increase adverse events. SDPs obviously do not induce TRALI and the risk of allergic reactions is significantly lower than for QFFP. Common to all three plasma types is that the time between donation and freezing the plasma, and whether plasma from whole blood or apheresis plasma is used as starting material, are decisive determinants for the clotting factor and inhibitor potencies in the final bags. Plasma frozen 3-6h after donation, and apheresis plasma, contain markedly greater amounts of clotting factors and inhibitors than plasma frozen 15-24h after collection or plasma from whole blood. Lyophilisation and the pooling of single-donor plasma units with ABO blood group in suitable proportions (Uniplas) facilitate SDP handling and logistics without loss of clinical efficacy. SDP is obviously at least as cost-effective as QFFP if non-infectious adverse events including TRALI are taken into account, at least in younger patients and patients with good prognosis.