Mechanisms of Trauma Coagulopathy. Dr B M Schyma Changi General Hospital Singapore

Transcription

1 Mechanisms of Trauma Coagulopathy Dr B M Schyma Changi General Hospital Singapore

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3 HAEMORRHAGE A continued cause of PREVENTABLE death. 24% of trauma patients are coagulopathic on arrival 1 56% of severe trauma patients have coagulation abnormalities at 25min (samples taken on scene) Time to Definitive Haemorrhage Control is a key determinant of outcome 3. 1) Brohi, J Trauma (2003) 2) Floccard et al, Injury (2012) 3) Macleod, J Trauma (2003)

4 Coagulopathy is the Harbinger of Mortality Pooled data from 5693 patients in 5 countries Samples taken on admission Number of Units in 24hrs 1) Frith et al, J Throm Haemost (2010)

5 The Triad of Death The Complete Story? HYPOTHERMIA CLOTTING FACTOR LOSS DILUTION CONSUMPTION CLOTTING FACTOR DYSFUNCTION COAGULOPATHY ACIDAEMIA

6 Hypothermia BUT..of 701,491 patients: Only 11,026 (1.57%) had an admission temperature < 35 C 1 1) Martin et al, Shock (2005)

7 ROTEM ROTEM CT: Time to initiation of fibrin formation Alpha Angle: Rapidity of Fibrin Build up and Cross Linking CFT: Clot Kinetics (2mm to 20mm) MCF: Clot strength

8 p < , r = 0.89 p < , r = 0.85

9 MCF (mm) Clot Strength ph

10 Dilution 1. Maegele, World Journal of Emergency Medicine (2010)

11 Clotting factor DEFICIENCY? 71 Patients, ISS > 15 Stratified to degree of hypoperfusion by base deficit Similar volume of crystalloid Venous sample taken on admission Factor assay 1) Jansen et al, J Trauma (2011)

12 Base Deficit Vs. Factor Activity 1) Jansen et al, J Trauma (2011)

13 However 76% factor activity remained in the normal range 42% of patients had no deficiency Factor 5 behaves differently Significant association between BD and factor activity for 2,7,9,10 &,11 No association between BD and Factor 5 Activity Lowest level of activity of all factors 54% had a level below normal range

14 An interesting juxtaposition A significant number of our trauma patients arrive with significant coagulopathy. Mechanisms traditionally thought to cause coagulopathy appear to only occur in extremes.

15 Is There Something Else?

16 This Next Slide May Contain The Sexiest Graph You Will See Today

17 1) Frith et al, J Throm Haemost (2010)

18 Similar Pattern with Mortality 1) Frith et al, J Throm Haemost (2010)

19 Potential Mechanism? Protein C Activated by Thrombin-Thrombomodulin Complex Inhibits Factors 5 & 8 Promotes Fibrinolysis Cohen et al 206 patients Serial Blood Samples at 6,12, and 24 hrs Stratified by Base Deficit and ISS 1. Cohen et al, Ann Surg (2012)

20 Increased Activation of Protein C Activated Protein C Levels Protein C Levels *p < 0.05

21 Associated with Decreased Factor 5 & 8 Factor Va Level Factor VIIIa Level *p < 0.05

22 Fibrinolysis FIBRINOGEN PLASMINOGEN Thrombin tpa PLASMIN CROSS LINKED FIBRIN FIBRIN DEGRADATION PRODUCTS

23 APC Associated with De-Repression of Fibrinolysis *p < 0.05

24 The Thrombin Switch SHOCK THROMBOMODULIN PROTEIN C THROMBIN THROMBIN- THROMBOMODULIN ACTIVATED PROTEIN C Fibrinolysis

25 Fibrinogen & Fibrinolysis Fibrinogen concentration falls quickly Low fibrinogen predictor of mortality at 24hrs and 28 days 1 Degree of fibrinolysis related to mortality 2 1. Rourke et al, J Thromb Haemost (2012) 2. Tauber et al, Br J Anaesth (2011)

26 What have we not talked about Platelets Limited knowledge of the role of platelets in Trauma Induced Coagulopathy Endothelial Dysfunction

27 Trauma Induced Coagulopaty (TIC) Imbalance of the Dynamic Equilibrium Between Procoagulant Factors, Anti-coagulant Factors, Platelets, Endothelium and Fibrinolysis 1 Multi-Factorial Acute Coagulopathy of Trauma Hyperfibrinolysis Factor Deficiency (Dilutional) (Acidaemia) (Hypothermia) 1. Frith and Brohi, Curr Opin Crit Care (2012)

28 Managing TIC Remember Identify the bleeding coagulopathic patient early. Classical tests of coagulation may not detect TIC Instigate Damage Control Resuscitation Haemostatic Resuscitation Haemostatic Packaging Minimal, Targeted, Crystalloid Administration Early High Ratio Component Therapy Address Fibrinolysis Point of care coagulation testing

29 FULL CIRCLE Khan et al patients Median ISS 35 (25-41) INTERN (International Trauma Research Network) Lactate and ROTEM analysed at 4, 8 and 12 units PRBC FFP:PRBC 2:3 Platelets & Cryoprecipitate at 6 PRBC

30 4 Unit Transfusions 8 Unit Transfusions 12 Unit Transfusions *versus time zero

31 ROTEM 5min Clot Amplitude (CA5) ROTEM Mean Clot Firmness (MCF) ROTEM Clotting Time (CT)

32 Resuscitation is not an end-point, it is a means to facilitating definitive management.

33 References (1) Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54: Floccard B, Rugeri L, Faure A et al. Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury. 2012;43: MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003;55: Frith D, Goslings JC, Gaarder C et al. Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations. J Thromb Haemost. 2010;8: Martin RS, Kilgo PD, Miller PR, Hoth JJ, Meredith JW, Chang MC. Injury-associated hypothermia: an analysis of the 2004 National Trauma Data Bank. Shock. 2005;24: Engstrom M, Schott U, Romner B, Reinstrup P. Acidosis impairs the coagulation: A thromboelastographic study. J Trauma. 2006;61: Maegele M. Acute traumatic coagulopathy: Incidence, risk stratification and therapeutic options. World J Emerg Med. 2010;1:12-21.

34 References (2) Jansen JO, Scarpelini S, Pinto R, Tien HC, Callum J, Rizoli SB. Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity. J Trauma. 2011;71:S435-S440. Cohen MJ, Call M, Nelson M et al. Critical role of activated protein C in early coagulopathy and later organ failure, infection and death in trauma patients. Ann Surg. 2012;255: Rourke C, Curry N, Khan S et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost. 2012;10: Tauber H, Innerhofer P, Breitkopf R et al. Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma: results of the Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study. Br J Anaesth. 2011;107: Frith D, Brohi K. The pathophysiology of trauma-induced coagulopathy. Curr Opin Crit Care. 2012;18: Khan S, Brohi K, Chana M et al. Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage. J Trauma Acute Care Surg. 2014;76:561-7; discussion 567.