title: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: US Army Institute of Surgical Research, Fort Sam Houston, Texas 78234-6315, USA.
authors.forename: Heather F
authors.initials: HF
authors.lastname: Pidcoke
authors.forename: Steve J
authors.initials: SJ
authors.lastname: McFaul
authors.forename: Anand K
authors.initials: AK
authors.lastname: Ramasubramanian
authors.forename: Bijaya K
authors.initials: BK
authors.lastname: Parida
authors.forename: Alex G
authors.initials: AG
authors.lastname: Mora
authors.forename: Chriselda G
authors.initials: CG
authors.lastname: Fedyk
authors.forename: Krystal K
authors.initials: KK
authors.lastname: Valdez-Delgado
authors.forename: Robbie K
authors.initials: RK
authors.lastname: Montgomery
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Reddoch
authors.forename: Armando C
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: James K
authors.initials: JK
authors.lastname: Aden
authors.forename: John A
authors.initials: JA
authors.lastname: Jones
authors.forename: Ron S
authors.initials: RS
authors.lastname: Bryant
authors.forename: Michael R
authors.initials: MR
authors.lastname: Scherer
authors.forename: Heather L
authors.initials: HL
authors.lastname: Reddy
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Goodrich
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
mesh_terms: D000328:Adult; D000094902:Blood Banking / Q000379:methods; D001793:Blood Preservation / Q000379:methods*; D058731:Blood Safety / Q000379:methods*; D001803:Blood Transfusion / Q000379:methods*; D017848:Blood-Borne Pathogens / Q000528:radiation effects; D015925:Cryopreservation / Q000379:methods; D006470:Hemorrhage / Q000628:therapy*; D006487:Hemostasis; D006489:Hemostatic Techniques; D006801:Humans; D007239:Infections / Q000097:blood* / Q000635:transmission; D017319:Photosensitizing Agents / Q000494:pharmacology; D015539:Platelet Activation / Q000528:radiation effects; D012256:Riboflavin / Q000494:pharmacology; D013916:Thrombelastography / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D017319:Photosensitizing Agents; D012256:Riboflavin