Int J Burn Trauma 2012;2(1):42-50
Original Article
Effects of in vitro hemodilution, hypothermia and rFVIIa addition on
coagulation in human blood
Daniel N Darlington, Igor Kremenevskiy, Anthony E Pusateri, Michael R Scherer, Chriselda G Fedyk, Bijan S Kheirabaldi, Angel
V Delgado, Michael A Dubick
US Army Institute of Surgical Research, Fort Sam Houston, Texas 78234, USA.
Received January 25, 2012; accepted February 15, 2012; Epub March 15, 2012; published March 30, 2012
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 µg/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.
(IJBT1201003).
Keywords: TEG, thrombin generation, PT, aPTT
Address correspondence to:
Daniel N Darlington, PhD
US Army Institute of Surgical Research
3698 Chambers Pass
Fort Sam Houston, TX 78234, USA.
Tel: 210-539-3761; Fax: 210-539-6244
E-mail: Daniel.darlington@amedd.army.mil
Original Article
Effects of in vitro hemodilution, hypothermia and rFVIIa addition on
coagulation in human blood
Daniel N Darlington, Igor Kremenevskiy, Anthony E Pusateri, Michael R Scherer, Chriselda G Fedyk, Bijan S Kheirabaldi, Angel
V Delgado, Michael A Dubick
US Army Institute of Surgical Research, Fort Sam Houston, Texas 78234, USA.
Received January 25, 2012; accepted February 15, 2012; Epub March 15, 2012; published March 30, 2012
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 µg/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.
(IJBT1201003).
Keywords: TEG, thrombin generation, PT, aPTT
Address correspondence to:
Daniel N Darlington, PhD
US Army Institute of Surgical Research
3698 Chambers Pass
Fort Sam Houston, TX 78234, USA.
Tel: 210-539-3761; Fax: 210-539-6244
E-mail: Daniel.darlington@amedd.army.mil
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