Interpreting the Coagulopathy of Trauma-Shock

Faculty Bryan A. Cotton, MD, MPH The University of Texas Health Science Center Houston, Texas Richard P. Dutton, MD, MBA University of Maryland School of Medicine R Adams Cowley Shock Trauma Center Baltimore, Maryland Martin A. Schreiber, MD, FACS Oregon Health & Science University Portland, Oregon

Mortality After Trauma Retrospective review of trauma death at level I trauma center (Stewart et al, 2003) Leading causes of death CNS, 51% Shock, 21% CNS + Shock, 16% Stewart RM, et al. J Trauma . 2003;54:66-71.

Time to Death Within 12 h of arrival to ED 50% of trauma patients are dead Within 48 h of arrival to ED ≈70% of trauma patients are dead Early interventions can impact a patient’s life Stewart RM, et al. J Trauma. 2003;54:66-71.

Coagulopathy and Mortality Retrospective review N=1867, 24.4% of patients significantly coagulopathic Coagulopathy defined as: 1.5 x normal Mortality Overall, 19.5% Noncoagulopathic, 10.9% Coagulopathic, 46% Brohi K, et al. J Trauma. 2003;54:1127–1130.

Coagulopathy and Mortality 100 Normal 80 Coagulopathy 60 40 Percent Mortality 20 0-14 15-29 30-44 45-59 59-64 Injury Severity Score Adapted from Brohi K, et al. J Trauma. 2003;54:1127–1130.

Acute Coagulopathy of Trauma

Acute Coagulopathy of Trauma 18 17 16 15 14 Prothrombin Time(s) 13 12 11 10 2.1 2.2-4.1 4.2-7.6 7.7 Base Deficit (mEq/L) Adapted with permission from Brohi K, et al. Ann Surg. 2007;245:812-818.

Shock as a Mechanism of Coagulopathy Adapted from Hoffman M. Blood Rev. 2003;17:S1-S5.

Base Deficit and Protein C 80 60 Thrombomodulin (ng/mL) 40 20 2.1 2.2-4.1 4.2-7.6 7.7 Base Deficit (mEq/L) Adapted with permission from Brohi K, et al. Ann Surg. 2007;245:812-818.

Base Deficit and Protein C Activated protein C is potent anticoagulant Activates fibrinolysis In shock state, protein C activation→coagulopathy Decrease in protein C concentration associated with marked increase in mortality Brohi K, et al. Ann Surg. 2007;245:812-818.

Protein C Pathway Binds protein C Produces activated protein C Thrombomodulin increased Binds protein C Produces activated protein C Inhibits factors V, VIII Accelerates fibrinolysis

Rate of Heat Transfer Q=mc(T2 - T1) Heat Transfer (kcal/hr) Rewarming Technique Heat Transfer (kcal/hr) Airway rewarming 8-12 Overhead radiant warmer 17 Heating blankets 20 Convective warmers 15-26 Body cavity lavage 36 Continuous arteriovenous rewarming 92-139 Cardiopulmonary bypass 710 Q=mc(T2 - T1) Gentilello LM. In: Maull KI, et al, eds. Advances in Trauma and Critical Care. Vol 9. St Louis, MO: Mosby; 1994:39-79.

Effect of Hypothermia and Dilution 27 25 23 Dilution 21 PT (sec) 19 17 No Dilution 15 13 28 30 32 34 36 38 Temperature (°C) Gubler KD, et al. J Trauma. 1994;36:847-851.

Changes of Plasma Fibrinogen Concentration and Platelet Count Porcine trauma model HCI-induced hypothermia and acidosis pH, 7.1 Temperature, 32°C Results: Increased hypothermia and acidosis significantly decreased fibrinogen concentration and PLT counts Martini WZ, et al. J Trauma. 2005;58:1002-1010.

Thrombin Generation 9000 Control 7500 Hypothermic µg/L) 6000 4500 Acidotic * [TAT] ( * * Combined 3000 * * * 1500 * * * * * * 1 2 3 4 5 6 7 Quench Time (min) *P.05, different from normal value at the same quench time point. Posted with permission from Martini WZ, et al. J Trauma. 2005;58:1002–1010. 16 16

Acute Coagulopathy of Trauma (ACOT) Hemorrhage Inflammation Resuscitation Shock Other Diseases Dilution Acidemia Medications Fibrinolysis Hypothermia Hypothermia Genetics Factor Consumption Coagulopathy ACoTS Hess JR, et al. J Trauma. 2008;65:748-754.

Conclusions Coagulopathy following trauma is complex Severely injured are coagulopathic immediately following injury Most of what we do makes it worse Early treatment should focus on stopping bleeding and correcting coagulopathy

Bryan A. Cotton, MD, MPH Associate Professor of Surgery The University of Texas Health Science Center and Center for Translational Injury Research Houston, Texas

Has the way in which you manage the coagulopathy of trauma changed considerably over the course of your career as a surgeon?

Historically Treatment delayed Resuscitation emphasized Currently Arrest bleeding Correct coagulopathy early Downplay resuscitation Adequate organ perfusion Limit fluids

Richard P. Dutton, MD, MBA Professor of Anesthesiology University of Maryland School of Medicine Attending Anesthesiologist R Adams Cowley Shock Trauma Center Baltimore, Maryland

In the upcoming year, what types of research can we expect to see disseminated in the medical literature concerning resuscitation methods and strategies for managing the coagulopathy of trauma, and what will be the focus of those papers?

Papers on role of recombinant factor VIIa in trauma Results from prospective, randomized trial expected ≈600 patients enrolled Third or fourth largest trauma study ever conducted Papers on plasma:red cell ratio Match therapy to patient Base ratio on needs of particular patient Prospective and randomized trials

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