In Vivo Bleeding Time and In Vitro Thrombelastography Measurements are Better Indicators of Dilutional Hypothermic Coagulopathy Than Prothrombin Time

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Abstract
The coagulopathy of trauma is generally confirmed by prothrombin time (PT) > or =16 seconds or an international normalized ratio > or =1.5. However, the utility of these values as a screening test is unknown. We examined different coagulation tests to determine the best predictor of coagulopathic bleeding and mortality in a small animal hemorrhage model. Coagulopathy was induced in male New Zealand White rabbits by warfarin (W; 2 mg/kg for 2 days; n = 7), or hemodilution and hypothermia (HH; 50% blood exchange with Hextend, 34.5 +/- 0.3 degrees C; n = 7). Normal (N) rabbits without pretreatment served as the control (n = 7). Blood samples collected after coagulopathy induction and analyzed by prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG) tests. Liver bleeding time (BT) was also measured before injury. An uncontrolled hemorrhage was created by a longitudinal splenic incision and the abdomen was closed. Rabbits were resuscitated with Hextend solution (25 mL/kg) to return blood pressure to baseline and monitored for 2 hours or until death at which time blood loss was measured. Warfarin-induced coagulopathy increased BT, PT, and aPTT. TEG showed increased reaction (R) and clot formation (K) times and marked decrease in clotting rate (alpha angle and Vmax). Hemodilution hypothermia coagulopathy increased only BT and aPTT, and decreased the clotting rate (alpha angle and Vmax) and strength of the clot. After injury, blood losses were higher in coagulopathic rabbits (W = 54.6 +/- 4.2 and HH = 51.1 +/- 8.9 mL/kg) than in normal rabbits (30.6 +/- 12.4 mL/kg) and resulted in 86%, 100%, and 0% death, respectively. BT and Vmax consistently predicted coagulopathic bleeding and death in all animals. Although satisfactory in warfarin-induced coagulopathy, PT was not a valid screening test for dilutional and hypothermic coagulopathy. BT and TEG measurements of blood clotting rate are better indicators of coagulopathic bleeding and mortality in this lethal hemorrhage model.