Plasma treated with amotosalen and ultraviolet A light retains activity for hemostasis after 5 days post‐thaw storage at 1 to 6^oC

Abstract

BACKGROUND Plasma thawed and stored at 1 to 6°C for up to 5 days (thawed plasma [TP]) provides rapid availability in emergencies and reduces plasma waste, but it carries risks of coagulation factor loss or activation, bacterial outgrowth, and viral contamination. We characterized changes in amotosalen/ultraviolet A (UVA) light pathogen‐reduced, fresh‐frozen plasma (FFP) and plasma frozen within 24 hours (PF24) with post‐thaw storage. STUDY DESIGN AND METHODS Amotosalen/UVA light‐treated FFP and PF24 were thawed after approximately 3 to more than 12 months of frozen storage and held at 1 to 6°C for 5 days. Global assessments of coagulation and hemostatic, antithrombotic, and activation markers indicative of function were assessed. RESULTS Day 5, thawed amotosalen/UVA light‐treated FFP and PF24 contained levels of Factors II, V, VIII, IX, X, von Willebrand factor ristocetin cofactor (vWF:RCo), fibrinogen, antithrombin III (ATIII), protein C, and protein S similar to the levels measured in Day 5 TP, as described in the Circular of Information. Thrombin generation was robust on Day 5 (amotosalen/UVA: FFP = 1866 ± 402 nM/minute; PF24 = 1800 ± 277 nM/minute). Most factor activities on Day 5, including von Willebrand factor‐cleaving protease (ADAMTS‐13), were more than 90% of Day 0 values, except for known labile Factors V and VIII and protein S. All units contained greater than 0.4 IU/mL protein S and α2 plasmin inhibitor on Day 5. Global functional indices, including thrombin‐antithrombin complexes, nonactivated thromboplastin time, and thrombin‐generation peak height, did not indicate activation of the coagulation cascade, although isolated units showed raised levels of Factor VIIa and Complement 3a. CONCLUSION Amotosalen/UVA light‐treated FFP and PF24 demonstrated retention of procoagulant and antithrombotic activity after 5 days post‐thaw storage at 1 to 6°C.

Thrombin generation potential and clot‐forming capacity of thawed fresh‐frozen plasma, plasma frozen within 24 h and solvent/detergent‐treated plasma (octaplasLG®), during 5‐day storage at 1–6°C

“…In the assay with high tissue factor concentrations, Erickson et al . demonstrated a decrease in the peak thrombin by mean of 26% in thawed PF24, during 5‐day storage at 1–6°C. In contrast, Cookson et al .…”

“…Matijevic et al [10] showed that although individual factor levels remained above 50% of normal levels in thawed FFP, after 5 days at 1-6°C, the TG potential decreased significantly by 58%, as demonstrated at low tissue factor concentrations. In the assay with high tissue factor concentrations, Erickson et al [11] demonstrated a decrease in the peak thrombin by mean of 26% in thawed PF24, during 5-day storage at 1-6°C. In contrast, Cookson et al [12] found unaffected amount of TG by storage of PF24 (produced from whole blood, RT-FP24) for 6 days, but there was an increase in lag time and decreased rate of clot formation by ROTEM.…”

Characterization of Ebola convalescent plasma donor immune response and psoralen treated plasma in the United States

“…The amotosalen/UVA treatment inactivates a broad spectrum of viruses, gram‐positive and gram‐negative bacteria, spirochetes, and parasites, including malaria . Prior clinical studies have demonstrated retention of coagulation factor activity and immunoglobulin levels after amotosalen/UVA treatment . We investigated whether PRT would significantly alter anti‐EBOV antibody concentrations and activity in the collected ECP units, as this could reduce the potential clinical benefit of ECP therapy.…”

In vitro quality of amotosalen‐UVA pathogen‐inactivated mini‐pool plasma prepared from whole blood stored overnight

“…TG has been evaluated in earlier studies to assess the hemostatic potential of TP treated with AUVA , MB , riboflavin or SD . Some of these studies reported modifications of the hemostatic potential of plasma after SD or MB treatment, while a marked effect was observed after use of the riboflavin‐UV process .…”