title: The whole is greater than the sum of its parts: hemostatic profiles of whole blood variants.
abstract: BACKGROUND
  Mounting evidence highlighting the benefits of hemostatic resuscitation has led to a renewed interest in whole blood (WB) and reconstituted WB (RWB). However, few data exist to characterize the clotting profiles of these variants. This study characterizes banked WB variants and RWB in standard 1:1:1 and 2:1:1 transfusion ratios of packed red blood cells, fresh frozen plasma, and platelets (PLTs). We hypothesized that the global hemostatic profile of 1:1:1 RWB is superior to 2:1:1 RWB and that PLT-modified WB (MWB) is superior to 1:1:1 RWB.
  
  
  METHODS
  Twenty-three units of packed red blood cells, fresh frozen plasma, and PLTs were obtained from the regional blood collection center and mixed to create 23 1:1:1 and 23 2:1:1 RWB units. Freshly donated WB units were obtained and used to create 11 of each nonmodified WB (NMWB) (room temperature and cooled) and MWB (room temperature and cooled) variants. International normalized ratio (INR)/partial thromboplastin time (PTT), complete blood cell count, functional studies, and an extensive panel of procoagulant and anticoagulant factor assays were performed on all products.
  
  
  RESULTS
  The 1:1:1 RWB had significantly lower INR and PTT (1.31 vs. 1.55, p = 0.0029; 42 seconds vs. 50 seconds, p = 0.0008) and higher activity of factors II, V, VII, VIII, IX, and X; antithrombin III, as well as protein C and higher fibrinogen levels than did 2:1:1 RWB (factor IX, 86% vs. 70%, p = 0.0313; fibrinogen, 242 mg/dL vs. 202 mg/dL, p = 0.0385). There were no differences in INR/PTT or factor activity between MWB and NMWB. However, MWB had greater maximum clot firmness (MCF) by rotational thromboelastometry tissue factor-activated extrinsic clotting cascade measures than did NMWB (MCF, 61 mm vs. 50 mm, p = 0.0031). MWB also had greater MCF by rotational thromboelastometry tissue factor-activated extrinsic clotting cascade measures than did 1:1:1 RWB (MCF, 61 mm vs. 45 mm, p = 0.0005).
  
  
  CONCLUSIONS
  Although 1:1:1 RWB had a superior clotting profile relative to 2:1:1 RWB, MWB exhibited even better global hemostasis than did 1:1:1 RWB. Characterization of factor-level and functional clotting differences between WB variants is imperative for understanding the clinical benefits of hemostatic resuscitation.
authors: From the Department of Surgery (L.Z.K., B.M.H., C.K.C., R.A.C., R.F.V., B.J.R., M.F.N., M.J.C.), San Francisco General Hospital and the University of California, San Francisco; Department of Laboratory Medicine (Y.D., S.P., M.P.B., S.P.), University of California, San Francisco; and Blood Systems Research Institute (Y.D., S.P., M.P.B., S.P.), San Francisco, California.
authors: Lucy Z
authors: LZ
authors: Kornblith
authors: Benjamin M
authors: BM
authors: Howard
authors: Christopher K
authors: CK
authors: Cheung
authors: Yelena
authors: Y
authors: Dayter
authors: Suchitra
authors: S
authors: Pandey
authors: Michael P
authors: MP
authors: Busch
authors: Shibani
authors: S
authors: Pati
authors: Rachael A
authors: RA
authors: Callcut
authors: Ryan F
authors: RF
authors: Vilardi
authors: Brittney J
authors: BJ
authors: Redick
authors: Mary F
authors: MF
authors: Nelson
authors: Mitchell Jay
authors: MJ
authors: Cohen
mesh_terms: D001777:Blood Coagulation / Q000502:physiology; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology*; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D019934:International Normalized Ratio; D010314:Partial Thromboplastin Time; D010949:Plasma / Q000502:physiology*; D013916:Thrombelastography