2. THE FORMAT
Context / definitions / theory
Resuscitation process / trials / monitoring our therapy / MTP / the
practical things
I WILL be asking questions, please don’t fall asleep
If you give ANY answer, you get chocolate
If you give the correct answer, you won’t get more chocolate, you just
look smarter
5. HAEMOSTATIC RESUSCITATION
Rapid correction of haemostasis-impairing factors such as:
Hypothermia
Hypocalcaemia
Acidosis
Resuscitation with a balanced combination of blood products, which
in combination, resembles whole blood, so as to avoid the dilutional
coagulopathy observed in the “traditional methods”
The goal is to ensure adequate tissue perfusion without worsening
coagulopathy
Component of ”Damage Control Resuscitation”
Also permissive hypotension
Also damage control surgery
6. THE THEORY SIDE OF
THINGS
Not only because “exams”,
but sometimes it’s nice
when things at least have
the appearance of making
sense.
7. WHAT’S IN THE BLOOD?
Cells
Red cells
White cells
Platelets
Plasma proteins
Alpha globulins
Beta globulins
Gamma globulins
Coagulation factors
Water and electrolytes
9. PLATELETS
Functions:
1. Vascular constriction
a. Autocoid factors
2. Formation of platelet plug
a. Adhesion
b. Secretion
c. Aggregation
d. Procoagulant activity
3. Coagulation process
a. Clot retraction
b. Fibrin stabilizing factor
14. HOW DO WE REPLACE
THESE PRODUCTS?
Does anyone really know?
15. QUESTIONS TO ASK OURSELVES.
What products should we use?
How much do we need?
How quickly do we need to replace it?
What ratio of products is best?
How do we know we’re correcting anything?
What are the down sides?
16. PACKED RED CELLS
Each 250ml bag has a HCT of 0.6
ACPD additives
Stored at 4 degree celcius
28 day storage
Biochemical changes
2,3 – DPG
17. FRESH FROZEN PLASMA
Plasma from a single donation
Rapidly frozen to -30 degrees
celsius after separation from red
cells
200 – 300mls containing all
plasma proteins (>0.7IU/ml of
factor VIII)
Needs thawing before
transfusing
10 – 20mls/kg will raise
coagulation factor levels 12 –
15%
18. PLATELETS
Either derived from multiple
donors or apheresis from a
single donor
200 – 300mls of plasma
containing around 240 x 109 per
unit of platelets
Stored at 22 degrees for 5 days
Expected increment > 20 x
109/L
19. CRYOPRECIPITATE
Thawing FFP at 4 degrees then
frozen
Comes from a pool of 4 – 5
donors
Thawed to 37 degrees right
before use
100 – 250mls of fibrinogen at
>140mg/unit, factor VIII
>70IU/unit and vWF in high
concentrations
Each unit is 20 – 40mls
10 units of cryoprecipitate
expected to raise fibrinogen
20. FIBRINOGEN CONCENTRATE
Freeze dried lyophilized
preparations of fibrinogen
(number of brands)
900 – 1400mg per vial
Quickly reconstituted
No crossmatch required
4g (eg 4 vials) usually increases
fibrinogen levels 1g/L
21. NOVO SEVEN
Indicated for the use in the
context of surgery for patients
with:
Haemophilia A or B with inhibitors
Congenital Factor VII (FVII) deficiency
Glanzmann’s thrombasthenia who have
decreased or absent response to
platelet transfusions
Adults with acquired haemophilia
Off label use in all other cases
Incidence of thrombosis:
0.2% in patients with congenital
haemophilia
4% in people with acquired
haemophilia
22. COLLOIDS
Colloid solution as 4% or 20%
Prepared from pooled human
plasma
40g/L or 200g/L
Is expensive in other countries
but “free” in Australia
SAFE trial and head injuries
23. CRYSTALLOIDS
Haemodilution decreases
concentration of clotting factors
and leads to coagulopathy
75% of crystalloid volume
distributes to interstitial space
No contribution to oxygen
transport
Exacerbation of acidosis with
saline
24. TRANEXAMIC ACID
Aminocaproic acid analogue
Competitively inhibits
plasminogen activation
Intravascular thrombosis
Use in trauma
Use in obstetrics
25. CALCIUM
Many blood products contain citrate
Essential co-factor in coagulation
cascade
Excitation contraction coupling
Aim for ionized calcium
>1.1mmol/L
28. PROMMTT STUDY (2013)
Multi-centered prospective cohort study with 905 patients
Early death of patients receiving more red cells than platelets /
plasma within the first 6 hours (mortality increased 3 – 4x)
Those receiving 1:1 transfusion of plasma/platelets to red cells
tended to survive
Survival benefit was concentrated on first 6 hours
Of those who survived beyond 24 hours, no mortality difference at 30
days
29. PROPPR TRIAL (2015)
Multi-centered RCT
680 patients randomized to 1:1:1 or 1:1:2 (plasma: platelets: red
cells)
4% improvement in absolute mortality with 1:1:1, but underpowered
Statistically significant mortality improvement from exsanguination
within the first 24 hours with the 1:1:1 group (9.2% vs 14.6%)
30. CRASH 2 TRIAL (2010)
Multi-centered international RCT with 20,211 patients in total
1g of TXA given in first 3 hours of trauma followed by 1g over the
following 8 hours
All cause mortality improvement was significant but small (14.5% vs
16%)
Larger improvement in patients who received it within 1 hour of
trauma
Increase in mortality for those who received it AFTER 3 hours
TXA group had lower rate of thrombosis and myocardial infarction
32. INR / PROTHROMBIN TIME
Measures integrity of extrinsic and final common pathways of
coagulation cascade
Factors II, V, VII, X and Fibrinogen
Calcium and thromboplastin added
Time for fibrin clot formation measured
9.5 to 13.5 seconds usually
INR is lab dependent and is PT converted to a ratio
33. ACTIVATED PARTIAL
THROMBOPLASTIN TIME
A more sensitive version of thromboplastin time with narrower
reference range
Evaluates the intrinsic and common pathways
Factors II, V, VIII, IX, X, XI, XII and Fibrinogen
Calcium and phospholipid emulsion added to sample time to clot
formation observed
Reference range 30 – 40 seconds
35. PLATELET COUNT
Some suggestion of keeping platelet count >10 x 109/L for bleeding
prophylaxis
As part of MTP regardless of platelet count
>50 x 109/L for procedural cover or in DIC
>100 x 109/L in intracranial haemorrhage
Does not reflect platelet inactivation!
36. HAEMOGLOBIN
Late marker in the acutely bleeding patient
Not apt to wait for a Hb nor use Hb alone as a transfusion trigger
Generally keep >7g/dL in patients without IHD
If bleeding, keep >10g/dL
Higher targets may be necessary if continuous haemodynamic
compromise until definitive surgical haemostasis achieved
37. DIRECT ORAL ANTICOAGULANTS
Levels are available for all 3 DOACs
Perhaps more relevance now that Idarucizumab exists
Prothrombinex is an option
Call the haematologists
38. TEG / ROTEM
Thromboelastography and rotational thromboelastometry
Global tests of haemostasis performed on whole blood as a POC
Assesses kinetics of clot formation, strength and dissolution
Used to manage bleeding and assess response to interventions made
Cup rotates vs pin rotates
46. WHAT NEEDS TO HAPPEN?
Airway, breathing and circulation; primary survey
Large central venous access for massive transfusions
Arterial access for repeated ABGs and ROTEMs
FAST scan and trauma survey
Designated communicator with the laboratory
Designated runner to obtain blood products
Lots of checking of blood products
Managing traffic with presence of inpatient teams
47. THE CONSIDERATIONS
Pre-allocated trauma team roles
Badges with team member’s name and said role
Limited physical space around the patient available
Communication barrier with high decibels and unfamiliar faces
Decision on when the patient is ”stable enough” to get to CT / OT /
NIISWA / ICU
48. PEOPLE TO NOT FORGET
When things start to look
like they’re getting under
control.
Mention white cells and talk about leukodeplelted blood at the end of this slide.
Adenine: prolongs shelf life to 35 days (energy substrate)
Citrate: decrease calcium to anticoagulate blood
Phosphate: buffers the pH
Glucose/dextrose: for Ebden-Myerhoff glycolysis pathway
Biochemical changes:
Decreased ATP
Increased potassium: impaired Na/K/ATPase
Increased lactate
Decreased sodium
Decreased calcium: essentially zero due to citrate
Decreased glucose
Decreased pH (6.8 at 28 days)
Increased free haemoglobin due to RBC lysis in storage
Factor VIIa
Recombinant protein
Tissue factor + factor VIIa + platelets leads to platelet aggregation and production of platelet-fibrin matrix, thus affording haemostatis (therapeutic end goal)
Needs to be dosed twice, 20 minutes apart and is very expensive, also needs platelets to function
Consider when patient has already had:
10 units of red cells / 8 units of FFP / 2 units of platelets / 2 units of cryoprecipitate
Warfarin / heparin reversed
TXA has been considered or given
Warmed > 35, pH . 7.2, platelets > 100, ad Fib greater than 1
Adverse effects: DVT / PE and other thromboembolic disease including coronary
Andexanet alpha coming soon – direct Xa inhibitors
Warfarin – prothrombinex / FFP / Vit K
Aspirin / ticagrelor – give platelets, ?role of desmopressin
Protamine for heparins
Survivor bias
American study with 33% penetrating trauma rate – not your everyday SCGH trauma call
The one RCT (PROPPR) was underpowered, unblinded, and of the groups the majority never even achieved their transfusion ratio targets.
Reduction of fibrinolysis was the proposed goal, but no attempt to measure fibrinolysis was made.
Tranexamic acid has an anti-inflammatory effect, which may account for some of the mortality difference (Volpi et al, 2015).
In the CRASH-2 trial, doctors could choose to randomize or not randomize based on treatment certainty. Also, of the dead patients, only approximately 5% had bleeding as a cause of death. Approximately half of the patients in the trial did not even require a transfusion. in short, there are serious methodology concerns.
Much of the trial intervention occurred in the pre-hospital environment, which makes it difficult to generalise the findings.
Very good for detecting hyperfibrinolysis which no other test can detect
Systematic review in 2011 only 9 RCTs, 8 in cardiac surgery, 1 in liver tnrasplants, none in trauma
Between TEG and ROTEM, different transfusions can occur depending on which algorithm is used
MCF reproducible with correlation to Plt counts and APTT -> transfusion requirements and mortality
If the patient arrests, they almost certainly need to be intubated and have bilateral chest drains to decompress any potential pneumothoraces