title: Effect of hemodilution on coagulation and recombinant factor VIIa efficacy in human blood in vitro.
abstract: BACKGROUND
  This study evaluates the effect of hemodilution by various common resuscitation fluids, and the efficacy of activated recombinant factor VII (rFVIIa) on coagulation parameters in human blood in vitro.
  
  
  METHODS
  Samples from normal healthy volunteers (n = 9) were hemodiluted from 0% to 90% with normal saline, or 0%, 40%, 60%, and 80% with 5% albumin, Hespan, Hextend, normal saline, or lactated Ringer's, and incubated at 37°C ± 1°C for 30 minutes with and without rFVIIa (1.26 μg/mL).
  
  
  RESULTS
  There was a strong correlation between the dilution of hemoglobin (Hb), platelets, or fibrinogen and coagulation parameters. Hemodilution 0% to 90% changed coagulation parameters (prothrombin time [PT], activated partial thromboplastin time [aPTT], and thromboelastography) in an exponential fashion; the greatest changes occurred after hemodilution lowered Hb <6 mg/dL, platelet count < 100,000/mm(3), and fibrinogen concentration <200 mg/dL. PT and aPTT were significantly prolonged after 60% and 80% dilution for all fluids. Hemodilution of 60% and 80% significantly decreased clot strength (maximum amplitude) and the kinetics of clot development (α angle) and increased the clot formation time (K). Hemodilution with Hextend and Hespan decreased maximum amplitude and α angle >5% albumin, lactated Ringer's, or normal saline. rFVIIa significantly improved PT at 60% and 80% dilutions, and aPTT at 80% dilution. There was a significant effect of dilution, but not fluid type, on the efficacy of rFVIIa to change PT and aPTT, and the onset of clotting (R).
  
  
  CONCLUSIONS
  We have strong in vitro evidence that Hb <6 mg/dL, platelet count <100,000/mm(3), and fibrinogen concentration <200 mg/dL can be used as indexes of hemodilution-induced coagulopathy. This study also shows that Hextend and Hespan tend to decrease the clotting ability >5% albumin or the crystalloids. rFVIIa significantly decreased PT at all dilutions and aPTT at the highest dilution. The effectiveness of rFVIIa on PT and aPTT was significantly affected by the degree of dilution, but not by the type of fluid.
authors: Damage Control Resuscitation and Blood Programs, US Army Institute of Surgical Research, San Antonio, Texas 78234-6315, USA. daniel.darlington@amedd.army.mil
authors: Daniel N
authors: DN
authors: Darlington
authors: Angel V
authors: AV
authors: Delgado
authors: Bijan S
authors: BS
authors: Kheirabadi
authors: Chriselda G
authors: CG
authors: Fedyk
authors: Michael R
authors: MR
authors: Scherer
authors: Anthony E
authors: AE
authors: Pusateri
authors: Charles E
authors: CE
authors: Wade
authors: Andrew P
authors: AP
authors: Cap
authors: John B
authors: JB
authors: Holcomb
authors: Michael A
authors: MA
authors: Dubick