Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018 (Commentary, p. 3026)

Atreya, Chintamani; Glynn, Simone; Busch, Michael; Kleinman, Steve; Snyder, Edward; Rutter, Sara; AuBuchon, James; Flegel, Willy; Reeve, David; Devine, Dana; Cohn, Claudia; Custer, Brian; Goodrich, Raymond; Benjamin, Richard J.; Razatos, Anna; Cancelas, Jose; Wagner, Stephen; Maclean, Michelle; Gelderman, Monique; Cap, Andrew; Ness, Paul

Each of the techniques results in a reduction of the content and/or activity of the pro-and anticoagulant proteins in plasma. In general, these reductions do not exceed 20% to 30%, and for many proteins the reduction is less than this. The most notable reductions are in fibrinogen and Factors (F) VIII and FV across all platforms; F IX and FXI, protein C, and large von Willebrand factor multimers with Mirasol; and protein S and antiplasmin with Octaplas. [39] [40] [41] [42] [43] [44] [45] There have been few investigations of these treatments on complement components; in an analysis of Intercept plasma, C 3a was found to be reduced. 45 It has been noted that the reductions, while significant, usually resulted in contents within the reference range. 39 The pooled nature of SD plasma greatly reduces the variability in content that can easily be demonstrated between different donors' plasma samples. 46 Cryoprecipitate may be prepared from Intercept and Mirasol plasma units to meet the minimum content requirements, although the effect of the treatment is still evident. 47, 48 In vitro analyses of the clotting system have generally demonstrated substantial retention of clinically relevant function. 42, 44 As might be expected from the reduced contents noted, the resulting fibrin strands are thinner (with resulting increased clot density and reduced permeability) with longer lag time for formation or prolonged time to lysis. 49 Multiple clinical trials have demonstrated expected outcomes with the use of these PR plasma samples. Prophylactic transfusion of Intercept plasma into congenitally deficient patients yielded expected increases in the deficient factor in circulation with anticipated half-lives. 39 Use of large volumes of Intercept plasma in plasma exchanges for thrombotic thrombocytopenic purpura or idiopathic thrombocytopenic purpura resulted in expected outcomes without generating adverse events or (new) coagulopathy. [50] [51] [52] Use of large volumes (approx. 2 L) of Intercept plasma in liver transplantation yielded the same outcomes as with quarantine plasma. [50] [51] [52] [53] The current formulation of Octaplas has not been reported to be associated with thrombotic events when used in large volumes as had been seen with the original version of SD plasma. 54 A theoretical question has been raised whether the reduced content these components might place massive transfusion recipients at increased risk of inadequate hemostasis and death. 55 One in vitro mixing study suggested that a 50% plasma replacement would be necessary before altering coagulation kinetics. 56 Several large, historically controlled experiences with Intercept plasma in trauma situations, however, have failed to show any impact on the need for other blood components, time to discharge or mortality. 32 These PR plasma samples have not been associated with increased adverse events after transfusion. 57 Because of the pooled basis of SD plasma, it is believed to carry a reduced risk of transfusion-related acute lung injury (TRALI) because of dilution of potentially offending antibodies. There have been no TRALI cases reported in more than 10 million Octaplas units transfused. 58, 59 If the existing risk of TRALI is greater than one in 5000, removal of this risk in itself makes use of SD plasma cost-effective. 60 This pooling, however, does increase the risk of early and wide dissemination of a nascent nonenveloped virus. 61 To date, there has been little uptake of