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.
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
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
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
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.