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Trauma Induced Coagulopathy
Dr. Abdul Gafoor. M.T
MD (Anesthesiology)
ICU - ALKHOR HOSPITAL
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.
Coagulation cascade
Feed back for hemostasis &
Hyperfibrinolysis
Mechanism in Trauma
Review of Mechanism
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.
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)
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
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%
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
Effect of hypoperfusion and
coagulopathy on mortality
Brohi K etal Ann of surg 2007;245:812-818
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
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
The Lethal sixpack
 Tissue Injury
 Shock
 Dilution
 Hypothermia
 Acidosis
 Inflammation
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
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
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
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
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
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
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
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.
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.
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.
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.
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.

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Trauma induced coagulopathy

  • 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.
  • 4. Feed back for hemostasis & Hyperfibrinolysis
  • 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.

Notas do Editor

  1. 210 patients cohort
  2. Changes in fibrinogen synthesis and breakdown in pigs after haemorrhage, hypothermia, and acidosis. Data from Martini and colleagues17 and Martini and Holcomb.18 *P&lt;0.05 compared with control values.
  3. 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
  4. Prolonged ACT,R time,K time,(reduced enzymatic hypocoagulability) low alpha angle,MA and G(platelet hypocoagulability and poor fibrin deposition
  5. %(Karlsson etal.Thromb.Hemost 2009)
  6. when compared to fibrinogen and rF2,rF3 in a porcine model(JTH2011) to control blood loss after liver injury.
  7. When compared with FFP,CF concentrates significantly reduced transfusion requirement in early(first6hrs)and late (after 24hrs)in trauma victims(Nienhaber etal Injury 2011
  8. 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 (&gt;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.