Trauma induced coagulopathy

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  • 210 patients cohort
  • Changes in fibrinogen synthesis and breakdown in pigs after haemorrhage, hypothermia, and acidosis. Data from Martini and colleagues17 and Martini and Holcomb.18 *P<0.05 compared with control values.
  • 1C Strong recommendation, low-quality or very low-quality evidenceBenefits clearly outweigh risk and burdens, or vice versaObservational studies or case seriesStrong recommendation but may change when higher quality evidence becomes available . 2C Weak recommendation, Low-quality or very low-quality evidenceUncertainty in the estimates of benefits, risks, and burden; benefits, risk and burden may be closely balancedObservational studies or case seriesVery weak recommendation; other alternatives may be equally reasonable
  • Prolonged ACT,R time,K time,(reduced enzymatic hypocoagulability) low alpha angle,MA and G(platelet hypocoagulability and poor fibrin deposition
  • %(Karlsson etal.Thromb.Hemost 2009)
  • when compared to fibrinogen and rF2,rF3 in a porcine model(JTH2011) to control blood loss after liver injury.
  • When compared with FFP,CF concentrates significantly reduced transfusion requirement in early(first6hrs)and late (after 24hrs)in trauma victims(Nienhaber etal Injury 2011
  • blunt trauma who survived for more than 48 hours, assigned to receive rFVIIa 200 μg/kg, after they had received eight units of RBCs, and a second and third dose of 100 μg/mg one and three hours later; had a reduction in RBC transfusion requirements and the need for massive transfusions (>20 units of RBCs), compared with placebo. Israeli guidelines based on findings from a case series of 36 patients who received rFVIIa on a compassionate-use basis in Israel [ 313 ] propose an initial dose of 120 μg/kg (between 100 and 140 μg/kg) and (if required) a second and third dose.

Transcript

  • 1. Trauma Induced Coagulopathy Dr. Abdul Gafoor. M.T MD (Anesthesiology) ICU - ALKHOR HOSPITAL
  • 2. Impact of TIC  Incidence:25-35 % of Trauma cases.  Mortality:3-4 fold higher in TI  24 hour mortality - 8 times higher (Brohi K et al Current Opin Crit Care 13:680-685:2007)  Higher transfusion requirements.  Longer intensive care unit and hospital stays.  More days requiring mechanical ventilation.  Greater incidence of multiorgan dysfunction.
  • 3. Coagulation cascade
  • 4. Feed back for hemostasis & Hyperfibrinolysis
  • 5. Mechanism in Trauma
  • 6. Review of Mechanism
  • 7. Acute Coagulopathy of Trauma Shock (ACoTS)  Syn:ETIC(Early Trauma Induced Coagulopathy)  Starts in the prehospital period.  Shock&Hypoperfusion is the cause.  Dilution,Hypothermia,Loss of coagulation factors not significant at this stage.  Thrombomodulin-ProteinC pathway is activated in hypoperfusion.  Hypercoagulable state and risk of thrombosis due to Protein C depletion.
  • 8. Risk factors  significant risk factors for life-threatening coagulopathy  injury severity score > 25  systolic BP < 70mmHg  acidosis with pH < 7.10  hypothermia with BT < 34℃  lethal triad  hypothermia, metabolic acidosis, progressive coagulopathy (Ferrara A etal Am J surg1990:160:515)
  • 9. Acidosis  Marker of inadequate tissue oxygen utilization  Duration of hypotension and acidosis related to abnormal coagulation  Treated by improving tissue oxygen delivery Brohi K etal Ann of surg 2007;245:812-818
  • 10. Dilution of clotting factors  Resuscitation fluid  Transfused PRBC are plasma poor  Factor replacement (FFP etc)often given late  Coagulation affected when factors are below 25%
  • 11. Hypothermia  Strong relationship between temperature and survival.Less than 32°C-100% mortality  Mild Hypothermia-platelet function reduced  Severe Hypothermia-Function of clotting factors reduced  PT,PTT performed routinely at 37°C do not reflect the real state and misleading
  • 12. Effect of hypoperfusion and coagulopathy on mortality Brohi K etal Ann of surg 2007;245:812-818
  • 13. Changes in fibrinogen synthesis and breakdown in pigs after haemorrhage, hypothermia, and acidosis. Fries D , Martini W Z Br. J. Anaesth. 2010;105:116-121 © The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org Role of Fibrinogen
  • 14. Loss and consumption of clotting factors  Clotting factors lost proportionate to duration of shock  Loss not a problem until IV fluids are administered  Massive tissue factor exposure in prehospital phase gives intense thrombosis  Thrombosis and fibrinolysis leads to consumptive coagulopathy  Clot formation and quality impaired
  • 15. The Lethal sixpack  Tissue Injury  Shock  Dilution  Hypothermia  Acidosis  Inflammation
  • 16. Sequence of clotting factors affected in bleeding Fibrinogen F1  Prothrombin F2  Factor F5  Factor F7  Platelets Hippala ST Anesth Analg 1995 Increased bleeding tendency if fibrinogen level is below1.5-2g/dl Critical Fibrinogen level may be reached before need for RBC
  • 17. Updated European guidelines  Target Hb of 7-9 g/dl. (Grade 1C).  Ionised calcium levels be monitored during massive transfusion. (Grade 1C) .If low CaCl2  FFP in a dose of 10-15ml/Kg(Grade 1B)  Platelets to maintain a platelet count above 50 × 10 9 /l. (Grade 1C). Above 100 × 10 9 /l in multiple trauma or TBI (Grade 2C) .Initially4-8 platelet concentrates or one aphaeresis pack. (Grade 2C). Crit Care 2010;14:R52
  • 18. Updated European guidelines  Single haematocrit measurements not a good marker for bleeding. (Grade 1B).  Serum lactate and base deficit are sensitive tests to estimate and monitor the extent of bleeding and shock. (Grade 1B).  PT,aPTT,INR,Fibrinogen and platelets estimation recommended((Grade 1C)  Thromboelastometry recommended(Grade 2C)  Maintain Normothermia Crit Care 2010;14:R52
  • 19. Updated European guidelines  If there is TEG signs of functional fibrinogen deficit  If Fibrinogen levels of 1.5-2gm/dl(level grade 1 C)  Initial dose of 3-4gms or 50mg/Kg  Repeated dose guided by TEG or lab assessment (grade 2 C) Crit Care 2010;14:R52 Fibrinogen
  • 20. Updated European guidelines  Antifibrinolytic agents be considered in the bleeding trauma patient (Grade 2C). In established hyperfibrinolysis(Grade 1B)  Tranexamic acid 10-15 mg/kg followed by an infusion of 1-5 mg/kg per hour or  ε-aminocaproic acid 100-150 mg/kg followed by 15 mg/kg/h(guided by thromboelastometry)  Aprotinine not recommended  Caution in renal failure Crit Care 2010;14:R52 Antifibrinolytics
  • 21. Updated European guidelines  Novoseven(rFVIIa) if major bleeding in blunt trauma persists despite standard attempts to control bleeding and best-practice use of blood components. (Grade 2C).  PCC for the emergency reversal of vitamin K- dependent oral anticoagulants. (Grade 1B).  Desmopressin (DDAVP) considered ONLY in refractory microvascular bleeding if the patient has been treated with platelet-inhibiting drugs such as aspirin. (Grade 2C).  Antithrombin concentrates not recommended. (Grade 1C). Crit Care 2010;14:R52
  • 22. Fibrinogen  Fibrinogen as low as 2gm found to reduce post operative blood loss upto 32%(Karlsson etal.Thromb.Hemost 2009)  ROTEM guided fibrinogen administration reduced transfusion rate and postoperative blood loss  Fibrinogen improved dilutional coagulopathy induced by HES by increasing clot firmness  Fibrinogen&PCC avoided PRBC transfusion in 29%patients when compared to FFP(3%)  Fibrinogen &PCC avoided platelet transfusion in 91%patients compared to FFP(56%). Scochi etal crit care 2011;15R83
  • 23. Prothrombin concentrate PCC  Initially used for immediate reversal of warfarin  PCC available in different concentration of ingredients in different commercial products. only factor 9 is standardised.  PCC contain prothrombin&factors 7,9,10  Prothrombin is the major thrombogenic agent in PCC.  Combination of PCC and Fibrinogen was found to be most effective in liver injury.
  • 24. Tranexamic acid  Blocks the lysine binding site of plasmine  CRASH 2 trial(Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage) showed Tranexamic acid reduced blood transfusion in a dose of 20mg/Kg  EACA (epsilon aminocaproic acid) another alternative.
  • 25. Fresh Frozen Plasma  FFP:RBC close to 1:1 ratio beneficial in massive transfusion.In nonmassive;1:2 optimum.  No RCTs,only retrospective data.  7 studies favoring high ratios(1:1) regarding mortality reduction;2 studies against.  Time for FFP thawing, a confounding factor.  Severity of injury another confounding factor(received more PRBC)  Each unit of FFP independently associated with 2.1%higher risk of MOF and 2.5%higher risk of ARDS.
  • 26. Recombinant Factor 7 rFVIIa (Novoseven)  Not a first line treatment  In blunt trauma ,when standard therapy fails.  In diffuse small vessel coagulopathic bleeding  Hct>24,Platelets>50000,fibrinogen 1.5-2gm/L and  Acidosis,hypothrmia&hypocalcemia corrected  First dose200mcg/Kg after 8 units PRBC  Second and Third dose100mcg/Kg ,1 and 8 hours later.
  • 27. Summary  TIC starts early in trauma (ACoTS)in the pre- hospital period and caused by shock, hypoperfusion & Inflammation  Aggravated by hypothermia,Acidosis,Dilution&loss of coagulation factors.  PT,PTT,INR,Hct unreliable in assessment.  Thromboelastometry highly recommended  Fibrinogen /cryoprecipitate highly recommended.  Prothrombin concentrates(PCC) to be considered.  Antifibrinolytics to be considered.  Novoseven for specific indications.