Haemostatic Resuscitation

1. Haemostatic
resuscitation
DR. FONSEKA
SCGH – ED
2018

2.  Vital Part of Damage control resuscitation in Haemorrhagic shock
1] Permissive Hypotension[Minimal Normotension]
2] Haemostatic Resuscitation [ Massive Transfusion Protocol]
3] Anatomical Haemorrhage control [ Damage control surgery ]

3. Hemostatic resuscitation –
 process of restoring and sustaining normal tissue perfusion in uncontrolled
hemorrhagic shock, with preservation of effective clotting
 until definitive anatomic control of hemorrhage is achieved, typically through surgery or
angiographic embolization
 Continued processes in a Patient with severe trauma

4. Major causes of death in trauma
 Traumatic Brain injury- Common –Determined at the time of injury
 Haemorrhage 40%- common and preventable
contributing causes for Shock in trauma
-Obstructive [tension pneumothorax and cardiac tamponade]
-Distributive shock [High spinal cord injury]
-Cardiac contusions/dysfunction

5. Injury associated Coagulopathy
1]Lethal Triad
 Coagulopathy-Dilutional-Fluids or unbalanced blood products , DIC
 Hypothermia- Exposure and Fluid administration
 Acidosis- Tissue injury and shock
2]Acute Traumatic Coagulopathy
3]Microparticle release and platelet dysfunction
4]Ongoing losses

6. Acute Traumatic coagulopathy
 impairment of hemostasis and activation of fibrinolysis that occurs early after injury
 in the absence of thrombocytopenia and hypofibrinogenemia
 biochemically evident prior to, and independent of, the development of significant
acidosis, hypothermia, or hemodilution
 INR > 1.5
 Thought secondary to significant activation of protein C
Inactivates Va and Viiia –Inhibiting X and Thrombin
 4 fold increase in mortality
 1-4 pts in every 10 patients with major trauma

7. Lethal triad
 Coagulopathy – ATC , 10% reduction in clotting factors for every 500ml
blood loss replaced by crystalloids/PRBC, DIC
 Acidosis – markedly reduce activity of V11 , Xa and Va
 Hypothermia - massive bleeding in conjunction with a core temperature of
<30°C is rarely survived . Secondary to platelet dysfunction –starts < 34 °C
and reduce CF function

8. Approach …

9. Guiding principles for resuscitation
 Resuscitation using IV fluids -only for hypotensive patients, only until
blood is available – To minimal Normotension
 Blood products -as soon as the need for transfusion is recognized
 Blood products should be given in equivalent amounts
 Thromboelastometry- rapid point-of-care assessment of coagulation
used to guide trauma resuscitation
 Anatomical control of bleeding

10. PROMMTT study-2013-US
 Prospective Observational multicentre major Trauma Study
 n=1245
 showed clear mortality benefit in 1st 24 hrs with blood product use in 1:1:1
ratios

11. PROPPR[RCT 2015]
 680 severely injured pts
 24- hour and 30-day mortality rates following trauma with severe bleeding
were not different when FFP, platelets and RBCs were transfused in a 1:1:1
or 1:1:2 ratio
 both groups similar complications rates were reported
 However, in the 1:1:1 ratio group the PROPPR investigators found a
reduced number of fatalities due to exsanguination

12. Massive transfusion protocol[MTP]
 When to activate
1.Anticipated severe haemorrhage from history before patient arrival
2.Code Red : When USS not available or History from Ambulance Crew
Systolic blood pressure <90 hgmm
Unresponsive to one fluid bolus
Suspected or confirmed massive haemorrhage
3.ABC score [Assessment of blood consumption Score] – 2 or more points
●Penetrating mechanism of injury
●Positive FAST (Focused Assessment with Sonography in Trauma) examination
●SBP of 90 mmHg or less
●Heart rate of 120 beats per minute (bpm) or greater

13. MTP
 Predefined and balanced transfusion products
 Aim to prevent coagulopathy while increasing O2 carrying capacity
 Data from war zones in Iraq and Afghanistan
replacement of >1 blood volume in 24 hours or >50% of blood volume in 4
hours

14. MTP-SCGH
 4 units RBC
 2 units FFP
 1 adult therapeutic dose platelet
 10 units cryoprecipitate if fibrinogen < 1.5 g/L

15. Antifibrinolytic agents- Tranexamic Acid
 Recommended within first 3 hours of Trauma
 CRASH2 Trial –RCT 2010 – Mortality benefit [Mortality 4.9% Vs 5.4%]
 May increase bleeding if given in > 3 hours of trauma
 1 g IV over 10 minutes and continue 1g/8 hours
 No Thromboembolic events

16. Do not forget calcium
 Calcium citrate – Lowers ionised Ca
 Citrate overload from Blood products- inevitable consequence of receiving massive
transfusion
 3mg in 1 unit PRBC
 Usually rapidly cleared by liver – Impaired in trauma pt.
 Normal iCa - 1.15-1.33 mmol/L
 Below < 1.1 mmol/L
long QT, dysrhythmias
negative inotropy and vasoplegia, hypotension
hypocoagulability
 Predicts Hospital Mortality

17. Calcium
 Measure every 15-30 minutes while resuscitating
 If iCa < 1mmol/L –replace with calcium chloride 1 g or 2 -3 g of calcium
gluconate

18. Parameters Values to aim for
Temperature >35 °C
Acid-base status ph >7.2, base excess <–6, lactate
<4 mmol/L
Ionised calcium (Ca) >1.1 mmol/L
Haemoglobin (Hb) This should not be used alone as
transfusion trigger; and, should be
interpreted in context with
hemodynamic status, organ &
tissue perfusion.
Platelet (Plt) >50 x 10
9
/L
PT/APTT <1.5x of normal
INR ≤ 1.5
Fibrinogen >1.0 g/L

19.  Patients on Anticoagulants ………

20. Reversing Anticoagulants
 A specific reversal agent/antidote
 DDAVP
 Drug removal from the circulation and/or gastrointestinal tract
 Prothrombotic - Prothrombin complex concentrates
and other Blood products

21. FFP
 Contains all coagulation factors
 One unit is 200- 250 ml [ from I unit whole blood]
 Dose 10-15 ml /Kg
 Given Stat in haemorrhage
 Stored at or below -25c
 Thawed in 10-30 minutes
 Expected to increase CFs by 2.5% to 10% per unit
 If PT/APTT > 1.5 times the normal needs 2-8 units

22. Cryoprecipitate
 Contains –Fibrinogen, Factors Viii,Xiii,vWF
 Fibrinogen is the 1st CF to reach critical low levels
 I unit is 10-20 ml
 Comes in premade pools [ 1 to 5 units in one pool]
 Dose 5- 10 units [ 50-200 ml]- may be 5 units / 5 kg BW in massive Trauma
haemorrhage
 Stored at -25c or below . Thawed in 10-30 minutes

23. Fibrinogen Concentrate
 Approved to use in pt. with congenital Fibrinogen deficiency
 No benefit over Cryoprecipitate in Trauma

24. Direct Reversal of Anticoagulants
 Dabigatran - Idarucizumab [2.5 g/50 mL (50 mL): $2100.00]
- 2.5 g IV x 2 :15 minutes apart – repeat once
- Haemodialysis
-PCC not recommended –used if antidote unavailable
-FFP and other blood products can be given as a Part of
MTP
 Warfarin - Vit K 5-10 mg IV [ takes 6-12 hours]
-PCC [ recommended 4 factors with factor Vll]
- FFP with 3 Factor concentrate

25.  direct factor Xa inhibitors - No antidote
- Can not be dialysed
- PCC and FFP
Reversal agents Under Development
 Andexanet alfa – For Xa inhibitors and LMWH reversal
 Ciraparantag- For Xa inhibitors, Direct Thrombin Inhibitors and LMWH

26. Prothrombinex – 3 factor combination
 provision of factors II, IX and X
 Available in Australia-Prothrombinex -VF
 Dosing is based on units of factor IX activity
 Correct INR with in 30 minutes
 30- 50 IU/ kg given IV

27. Protamine
 Reversal of Heparin
 Heparin inactivates Thrombin and Xa
 1mg / 100 units of Heparin [ 25-50 mg IV ]
 For Enoxaparin given within 8 hours 1 mg / 1mg
Given > 8 hours ago 0.5mg/1mg
 SE -anaphylaxis in individuals who have previously been exposed to
protamine [ DM , Fish allergy]

28. rFVII concentrate
 Off – label use in Traumatic Haemorrhage
 Only approved for Haemophilia and Platelet functional disorder associated
bleeding
 Available research – No mortality benefit
- May reduce amount of transfusions
- May increase Thromboembolic risk
 shows significant potential and appears to be safe in young, previously healthy
individuals with traumatic haemorrhage

29.  Desmopressin (DDAVP)
-Synthetic analogue of ADH
-Increase release of Factor Vlll and vWF from platelets and
endothelial cells
-Used mostly for intra-op microvascular bleeding in vWF deficiency or
suspected platelet dysfunction in uraemia

31. Anatomical Control of bleeding
 Internal bleeding – manage as appropriate –
OT -damage control surgery/ Angiographic embolization
Pelvic binder
Reduce and splint long bone fractures
Cross clamp aorta
IABP
 External bleeding
Direct Pressure
Staples to scalp wounds
Tourniquet
Ligate vessels
Folly catheter

32. Damage controlled surgery
Aims
-Arrest bleeding
-Limit contamination
-Maintain blood floor to organs and extremities
-Continue resuscitation in ICU
-Delayed definitive surgical management once patient is stable

34. What if TBI or SCI in the same patient?
 Minimal Normotention [ 70-90 hgmm SBP . MAP 50-65 hgmm . Mentation ,
Radial pulse ]?
 Controversial
 Some resuscitates to above
 Some recommend MAP 85-90 hgmm
 Therefore should be individualised
 Maintain haemostasis
 Vasopressors may be needed in refractory Neurogenic shock once
haemorrhagic shock is excluded or treated to the best possible level

35. Monitor Progress on Haemostasis?
Time Critical assessments …
 Clinical assessment and
HR , BP , Pulseoxymetry , GCS, UOP
 ROTEM
 Base excess, Lactate , iCa , Hb

36. Is it Really Working ?
Activation of Coagulation and inflammation of trauma study
 Prospective cohort study – 2014 International Trauma Research Network
 106 pts. receiving MTP- Trauma centres UK and Norway
 ROTEM and Lactate measurements
 Shows No improvement of lactate and showed worsening of Coagulopathy
But –
-High Ratios RBC:FFP:Platelets were not achieved until late in resuscitation
-Crystalloids were administered
-PROMMTT study 2013 n=1245 showed clear mortality benefit in 1st 24 hrs with 1:1:1
ratios

37. Rotational Thromboelastometry

38.  Shows limited abnormalities of initial phase of coagulation
 Main use is monitoring Heparin, warfarin and haemophilia
 Takes 40-45 minutes
Coagulation Profile….

39. ROTEM…
 information within 5 minutes
 Real-time measurements using whole blood
 guide coagulation therapy according to actual needs
 Reduced transfusion requirements
 Reduced transfusion related adverse events
 Improved outcomes
 Used in various clinical settings – liver transplant, cardiac surgery, obstetrics &
trauma
 High negative predictive value –If normal results -bleeding highly unlikely due
to significant coagulopathy
 Provide information in overall haemostasis even one component is lacking –
Low platelets compensated by high Fibrinogen
 Lacks data on effects of DOACs

40. PT
INR
aPTT
II,VII,IX,X
EXTEM
INTEM
FIBTEM
HEPTEM
Primary
pathway
V, Platelet, Ca
Viii, plat,
ca
Dabigatran
RIVEROXABAN

42. Time from onset of clotting to 20mm amplitude
Alpha < measure rapidity of fibrin buil up and cross link
20mm
90mm

43. SCGH- MTP & ROTEM Algorithm for Critical
Bleeding&
 http://scghed.com/wp-content/uploads/2017/05/Massive-Transfusion-Protocol-2017.pdf

44. Summary …
 Early recognition and appropriate resuscitation
 Varies according to individual and injuries
 Involve all relevant specialities early-Early definitive Mx of haemorrhage
 Damage control resuscitation
 Use ROTEM/ continue to monitor – Clinical, BA, Lactate, Ca
 Tranexamic acid < 3 hours
 Modifications in-Head injury , Spinal injury
 Complications of MT

45.  Thank you !