Effects of In Vitro Hemodilution, Hypothermia and rFVIIa Addition on Coagulation in Human Blood

Abstract : Introduction: Coagulopathy can occur after hemorrhage, trauma and resuscitation, and has been associated with dilution of coagulation factors and hypothermia. Recombinant activated Factor VII (rFVIIa) has been used, often as a last resort, to improve hemostasis in trauma/hemorrhage patients with coagulopathy. The aim of this study was to further characterize the effects of rFVIIa on various coagulation parameters and the influence of temperature and hemodilution. Methods: Whole blood from healthy human volunteers was incubated in a combination of three conditions: undiluted or diluted 40% with either lactated Ringer s solution or Hextend, at 37 C or 34 C, and with and without rFVIIa (1.26 g/ml, final concentration). Blood or plasma, as appropriate, was measured for coagulation by thrombin generation, thromboelastography (TEG), prothrombin Time (PT) and activated partial thromboplastin (aPTT). Results: Incubation of plasma at 34 C significantly elevated thrombin generation, and prolonged PT and aPTT. Dilution of blood or plasma with 40% Hextend, but not lactated Ringer s, had a significant effect on TEG parameters, and prolonged PT and aPTT. In control conditions (37 C, 0 dilution), the addition of rFVIIa to human plasma or whole blood led to a significant change in all TEG parameters, and Lagtime for thrombin generation, but not to PT or aPTT. Conclusion: Theses data show that thrombin generation is affected by hypothermia, but not 40% dilution. TEG is affected by 40% dilution with Hextend, but not by hypothermia. PT and aPTT are significantly affected by both hypothermia and dilution. Recombinant FVIIa caused a greater change in thrombin generation at 34 C as compared to 37 C, and a greater change in PT at 40% dilution, suggesting that the effect of rFVIIa on coagulation is both temperature and dilution dependant.