Primary hemostatic capacity of whole blood: a comprehensive analysis of pathogen reduction and refrigeration effects over time

Abstract

BACKGROUND Whole blood (WB) has been used in combat since World War I as it is readily available and replaces every element of shed blood. Component therapy has become standard; however, recent military successes with WB resuscitation have revived the debate regarding wider WB use. Characterization of optimal WB storage is needed. We hypothesized that refrigeration preserves WB function and that a pathogen reduction technology (PRT) based on riboflavin and ultraviolet light has no deleterious effect over 21 days of storage. STUDY DESIGN AND METHODS WB units were stored for 21 days either at 4°C or 22°C. Half of each temperature group underwent PRT, yielding four final treatment groups (n = 8 each): CON 4 (WB at 4°C); CON 22 (WB at 22°C); PRT 4 (PRT WB at 4°C); and PRT 22 (PRT WB at 22°C). Testing was at baseline, Days 1–7, 10, 14, and 21. Assays included coagulation factors; platelet activation, aggregation, and adhesion; and thromboelastography (TEG). RESULTS Prothrombin time (PT) and partial thromboplastin time increased over time; refrigeration attenuated the effects on PT (p ≤ 0.009). Aggregation decreased over time (p ≤ 0.001); losses were attenuated by refrigeration (p ≤ 0.001). Refrigeration preserved TEG parameters (p ≤ 0.001) and PRT 4 samples remained within normal limits throughout the study. Refrigeration in combination with PRT inhibited fibrinolysis (p ≤ 0.001) and microparticle formation (p ≤ 0.031). Cold storage increased shear-induced platelet aggregation and ristocetin-induced platelet agglutination (p ≥ 0.032), as well as GPIb-expressing platelets (p ≤ 0.009). CONCLUSION The in vitro hemostatic function of WB is largely unaffected by PRT treatment and better preserved by cold storage over 21 days. Refrigerated PRT WB may be suitable for trauma resuscitation. Clinical studies are warranted.

Refrigerated Platelets for the Treatment of Acute Bleeding

“…Refrigerated PLTs are cleared over 2 to 3 days; thus, they certainly remain in circulation long enough to contribute to hemostasis during the crucial initial period after injury (10). Furthermore, recent data suggest that 4C-PLTs retain hemostatic function for at least 10 days when refrigerated (12,14). In the context of remote damage control resuscitation, whole blood or PLT units could be collected at support bases or forward locations and transported to remote sites in isothermal transport boxes (e.g., Golden Hour boxes) along with other blood products and medications.…”

In vitro Analysis of the Hemostatic Properties of Whole Blood Products Prepared with a Platelet-Sparing Leukoreduction Filter

“…The EXTEM MCF, used as a surrogate for platelet function, decreased over time. Though direct measurement of platelet function using aggregometry was not performed during the missions, the authors had previously reported on platelet aggregation [22]. Platelet function decreased significantly over time in CWB sample with a 50% loss from day 1 to day 5 with another 50% drop between days 5 and 10.…”

Trauma Hemostasis and Oxygenation Research Position Paper on Remote Damage Control Resuscitation

“…(41, 42) Refrigeration of CWB after pathogen reduction could ensure wide availability, hemostatic efficacy and enhanced safety in far forward settings, but must be weighed against its logistic burden. (43)…”

“…(43, 78–80) The need for a practical way to provide hemostatically functional platelets to support RDCR suggests that platelet and whole blood refrigeration should be re-examined. The current standard of platelet storage, and by extension, limitation on whole blood use, is impractical for RDCR.…”