Coagulation dysfunctions insevere trauma D. Săndesc “V. Babes” University of Medicine and Pharmacy Timisoara, Romania
Coagulation dysfunctions insevere trauma • Main topics: 1. What is the acute coagulopathy of severe trauma(pathogenesis): A primary phenomenon or a secondary one (dilution, hypotermia, acidosis)? 2. The new treatment recommendations
The crucifixion of Jesus: Review of hypothesized mechanisms of death and implications of shock and trauma-induced coagulopathy • “Trauma-induced coagulopathy may have been a contributing factor, if not the primary factor, in Jesus’ death. • It would explain how Jesus’ death could occur so rapidly, namely 6 hrs, rather than several days. It would also explain how blood could flow from Jesus’ corpse when his chest was impaled by the spear.” Joseph W. Bergeron MD. Available online 12 July 2011
Acute coagulopathy of trauma –clinical definition • “ … a syndrome of non-surgical bleeding from mucosal lesions, serosal surfaces, wounds and vascular access sites that continues after identifiable vascular bleeding has been controlled” * Hess JR, Lawson JH. The Coagulopathy of Frida Kahlo Trauma. .J Trauma 2006; 60: S12-S19
Bleeding in trauma – epidemiology (2) Frida Kahlo, “The broken column” • Journal of Trauma-Injury Infection & Critical Care. Early Massive Trauma Transfusion: Current State of the Art. 60(6) Supplement:S3-S11, June Journal of Trauma-Injury Infection &Critical Care.) Supplement:S3S11, June 2006 2006 .”
Bleeding in trauma – epidemiology (4) Journal of Trauma-InjuryInfection & Critical Care.54(6):1127-1130, June 2003.
Coagulation dysfunctions insevere trauma • Main topic: what is the acute coagulopathy of severe trauma: A primary phenomenon or a secondary one (dilution, hypotermia, acidosis)?
The classical paradigm:Acutecoagulopathy of trauma –a secondary phenomenom Coagulopathy Death Acidosis Hypothermia Hemodilution Brohi, K, et al. J Trauma, 2003.
Instigators of the coagulopathy in trauma: hemodilution • Bleeding, volume therapy, transfusions • German study: • coagulopathy present in 50% of patients that received> 3 l in prehospital • role of the type of solutions in coagulopathy(HES)1 • London study:2 • simillar incidence of coagulopathy with german study • minimal prehospital fluid administration (500 ml media) • Hemodilution: contributor, not instigator factor 1. Brazil EV, Coats TJ. Sonoclot coagulation analysis of in-vitro haemodilution with resuscitation solutions. J R Soc Med 2000; 93:507–510. 2.Brohi K, Singh J, Heron M, et al. Acute traumatic coagulopathy. J Trauma 2003; 54:1127–1130.
Instigators of the coagulopathy in trauma: hypotermia • Influence on coagulation factor’s activity • Influence on platelet’s function1 • Significant effects on coagulation: only at temperatures bellow 330C 2 • Severe hypotermia: only in 9% of trauma patients 1. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: Hypothermia and acidoses revisited. J Trauma. 1997;42:857–861. 2.Shafi S, Elliott AC, Gentilello L. Is hypothermia simply a marker of shock and injury severity or an independent risk factor for mortality in trauma patients? Analysis of a large national trauma registry. J Trauma 2005; 59:1081–1085.
Instigators of the coagulopathy in trauma: acidosis • Considered “clasically” the most important instigator of the coagulopathy in trauma • Hydrogen ions: interface with ionic interactions of coagulation factors and activated plateletes1 • But it is difficult to separate the effects of acidemia per se from the effects of shock Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M. . J Trauma. 1997;42:857–861.
A new paradigm: Acute coagulopathy of trauma-a primary phenomenon Main instigator of the acute coagulopathy of trauma : Shock/hypoperfusion
Acute coagulopathy in trauma –new paradigm: Anticoagulation Acute coagulopathy of trauma:mechanism, identification and effect.Brohi, Karim; Cohen, Mitchell; Davenport, Ross Current Opinion in Critical Care. 13(6):680-685, December 2007.
Acute coagulopathy in trauma –new paradigm: Hyperfibrinolysis Acute coagulopathy of trauma: mechanism, identification and effect.Brohi, Karim; Cohen, Mitchell; Davenport, RossCurrent Opinion in Critical Care. 13(6):680-685, December 2007.
A new paradigm: Acute coagulopathy of trauma-a primary phenomenon Shock / Tissue hypoperfusion Acidemia Dilution Hypotermia Endothelium (genotype?) TM ↑ PC tPA ↑ Subendothelial type III collagen TF TM / Thrombin complex Thrombin ↓ aPC Von Willebrand Platelets Coagulation cascade PAI-1- V- VIII- PAI-1 ↓ Hypocoagulation Hyperfibrinolysis Consumption
LATE HYPERCOAGULABILITY AND THROMBOSIS RISK • Hypercoagulable state in severe trauma patients-in a few days • A possible explanation:protein C depletion • Risks of thrombosis Schreiber MA, Differding J,Thorborg P,et al. J Trauma 2005; 58:475- 480.
Coagulation management in severe trauma: new evidences and challlenges • “Damage Control Hemostatic Resuscitation”:Massive early transfusions protocols in a 1:1:1 ratio (red cells/ plasma/platelets) • Whole Warm Blood • Antifibrinolytics-Tranexamic acid
Massive early transfusions protocols in a 1:1:1 ratio(packed red blood cells/ fresh frozen plasma/platelets): DAMAGE CONTROL HEMOSTATIC RESUSCITATION Massive Transfusion: New Insights.Sihler, Kristen; MD, MS; Napolitano, Lena; MD, FCCP Chest. 136(6):1654-1667, December 2009. 6
Massive early transfusions protocols in a 1:1:1 ratio (packed red blood cells/ fresh frozen plasma/platelets) .Coagulation management in massive bleeding.Griffee, Matthew; DeLoughery, Thomas; Thorborg, Per Current Opinion in Anaesthesiology. 23(2):263-268, April 2010 2
Warm Fresh Whole Blood • Retrospective, 354 pts transfused ≥10 U of RBCs • Compared patients transfused • Fresh Whole Blood + (PRBC, FFP) • Stored components (PRBC, FFP, aPLTs) • Groups compared equal in: • Age, severity of injury • Admission vital signs and labs, RBC amount • Average patient was in hemorrhagic shock • Base deficit of 6 and INR of 1.4 Spinella, PC, Perkins, JG, et al “Association of Warm Fresh Whole Blood with Survival” J Trauma. 2009; 66;S69-S76
Kaplan Meier Curve of 30 day survival Warm Fresh Whole Blood Blood Components Therapy WFWB group CT group Log rank test, p= 0.002
Potential mechanisms for WFWB association with improved survival • Improved function of RBCs, plasma, platelets in WFWB • Thoroughly documented - Increased storage time for all blood products leads to decreased function 1-4 • Old RBCs • hyperinflammatory, immunomodulatory, impair vasoregulation, poor O2 delivery • Increased anti-coagulants and preservatives in stored components 1 Spinella PC, Crit Care Med, 2007 2 Napolitano LM, Crit Care Clinics, 2004 3 Lavee J, J Thor CardiovSurg, 1989 4 Mohr R, J Thor CardiovSurg, 1988
Damage Control Hemostatic Resuscitation 30 21 29 33
“Damage Control Resuscitation represents the most important advance in trauma care for hospitalized civilian and military casualties from this war.” Cordts, Brosch and Holcomb, J Trauma, 2008
Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial • 274 hospitals; 40 countries; 20 211 adult patients • within 8 h of injury:-tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) OR -placebo. • All-cause mortality significantly reduced with tranexamic acid (p=0·0035). • The risk of death due to bleeding was significantly reduced (p=0·0077). www.thelancet.com Published online June 15, 2010 DOI:10.1016/S0140-6736(10)60835-5
CRASH-2 TRIAL: Conclusions • “Tranexamic acid safely reduced the risk of death in bleeding trauma patients • …tranexamic acid should be considered for use in bleeding trauma patients.” www.thelancet.com Published online June 15, 2010 DOI:10.1016/S0140-6736(10)60835-5
www.atitimisoara.ro • CURSUL NATIONAL DE GHIDURI SI PROTOCOALE IN ANESTEZIE-TERAPIE INTENSIVA SI MEDICINA DE URGENTA, a XIII-aEditie • EUROPEAN SOCIETY FOR INFORMATION AND TECHNOLOGY IN ANESTHESIA, INTENSIVE CARE AND EMERGENCY, ANNUAL MEETING • CONFERINTA NATIONALA DE PALIATIE • Timisoara, 23-25 Octombrie 2014