This document outlines the pathophysiology of blood loss and massive transfusion. It discusses hemostasis, the body's response to blood loss, trauma-induced coagulopathy, assessment of blood loss, hemostatic monitoring including viscoelastic tests, definitions of massive transfusion, indications and management including massive transfusion protocols, component ratios, and targets. It also covers special considerations for pediatric, obstetric, and liver disease populations.

1. Pathophysiology of blood loss
and massive transfusion
Presenter: DR. Getaye S.(ACCPMR2)
9/8/2022 1

2. Outlines
Objectives
Introduction
 Hemostatic Monitoring
Massive blood transfusion and MTPs
Massive transfusion complications and their
managements
References
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3. Objectives
understand mechanism of blood loss and
hemostasis
Know indications MBT, associated complications
and their management.
Summarize the institutions protocols for massive
blood transfusion.
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4. Introduction
Hemostasis
an ordered enzymatic process involving cellular
and biochemical components
preserve the integrity of the circulatory system
after injury
The ultimate goal:
 limit blood loss,
 maintain intravascular blood flow,
promote revascularization after thrombosis.
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5. Cont,
is a constant balance between procoagulation
processes and inhibition of uncontrolled thrombus
propagation.
Vascular endothelium, platelets, and plasma
coagulation proteins play equally important roles
in this process.
Healthy endothelial cells possess antiplatelet,
anticoagulant, and profibrinolytic effects to inhibit
unprovoked clot formation
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6. Cont,
Vascular endothelial injury—mechanical or
biochemical—leads to:
a) Vascular constrictions
b) platelet deposition at the injury site… primary
hemostasis(platelet mediated).
 this initial platelet plug may prove adequate for a minor
injury,
c) control of more significant bleeding needs stable clot
formation crosslinked with fibrin… secondary
hemostasis
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7. Cont,
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8. Cont,
Intrinsic Anticoagulant Mechanisms
Once coagulation is activated, regulation of hemostasis
essential to limit clot propagation
Flowing blood and hemodilution…early
more robust counter-regulatory mechanisms
Derangements in this delicate system can lead to
either excessive bleeding or pathologic thrombus
formation.
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9. Cont,
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10. Cont,
Blood loss
Blood loss is effusion of blood from
cardiovascular structures
It may be to the external or internal
Classes of Hemorrhage….
For the purpose of early detection and intervention,
ACS developed 4 classes of hemorrhage based on the
volume of blood loss and the physiologic responses
that follow
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11. Cont,
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12. Cont,
significant hemorrhage will cause
Imbalance oxygen delivery and oxygen consumption.
hemodynamic instability
decreased oxygen delivery and cellular hypoxia.
Hemorrhagic shock is a common and treatable
cause of death in trauma & other critical care
setting
second only to traumatic brain injury as the leading
cause of death from trauma
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13. Cont,
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14. Cont,
Physiologic response to blood loss
Early compensatory responses to blood loss occurs at
macrocirculatory level
Mediated by neuroendocrine system w/c include
progressive vasoconstriction of cutaneous, muscular,
and visceral vessels
The usual response to acute circulating volume
depletion is an increase in heart rate in an attempt to
preserve CO.
tachycardia is the earliest measurable circulatory
sign of shock.
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15. Cont,
The release of endogenous catecholamines
increases SVR, which in turn increase DBP and
reduces pulse pressure.
However, this does little to increase organ
perfusion and tissue oxygenation.
 Pain, haemorrhage, and cortical perception lead
to the release of hormones and other
inflammatory mediators
 sets the stage for the microcirculatory response.
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16. Cont,
For patients in early hemorrhagic shock,
venous return is preserved to some degree.
But the compensatory responses &Volume
repletion will allow recovery from the shock
state only when the bleeding has stopped.
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17. Cont,
At the cellular level, inadequately perfused
and poorly oxygenated cells are deprived of
essential substrates for normal aerobic
metabolism.
shift to anaerobic metabolism.
 subsequent end-organ damage and multiple
organ dysfunction may result.
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18. Compensatory
sympathetic
discharge
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19. Cont,
Trauma-induced coagulopathy.
clinical syndrome caused by the imbalance between
the clotting, anticoagulation and fibrinolysis
processes
Characterized with early hypercoagulation state
followed by hyperfibrinolysis
Closely related to the outcome of trauma patients
(associated with at least a twofold to fourfold
increase in mortality)
Nearly 1/3rd of patients present with TIC
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20. Cont,
TIC is the sum of two distinct processes:
a) Acute coagulopathy of trauma
due to activation of endogenous coagulations factors
b) Resuscitation-induced coagulopathy
Due to resuscitation processes and metabolic changes
So Coagulopathy develops from:
Consumption/loss of coagulation factors via
hemorrhage,
 hemodilution with resuscitation fluids,
Coagul. dysfunction from acidosis and hypothermia.
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21. Cont,
Trauma-induced coagulopathy is acutely
worsened by the presence of acidosis and
hypothermia.
The activity of coagulation factors, fibrinogen, and
platelet quantity are all adversely affected by
acidosis
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22. Early response
Subsequent response
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23. Cont,
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24. Cont,
Measurement of Blood Loss
important for assessing the need for both the initial and
subsequent blood transfusions
A standard approach includes a combination of
visualization and gravimetric measurements based on
weight differences between dry and blood-soaked
gauze pads.
 The accuracy of measurements is not uniformly
consistent and no “gold standard” for blood loss
quantification exists
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25. Cont,
ASSESSMENT OF THE HEMOSTATIC function
Given the importance of coagulopathy in the bleeding pts,
assessment of the hemostatic system is essential
Includes
taking medical history,
doing targeted clinical evaluation,
standard laboratory-based coagulation tests,
and viscoelastic monitoring
Standard coagulation lab. tests typically include PT, INR,
aPTT, and platelet count(some settings fibrinog level and
TT)
Limitations?
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26. Cont,
A recent meta analysis concluded that standard
plasma coagulation tests are not supported by strong
evidence for the management of perioperative
coagulopathic bleeding.
This is where viscoelastic monitoring brings added
value.
Viscoelastic coagulation monitoring devices like
RapidTEG and ROTEM assess the whole coagulation
process
significantly improve the coagulation ass.t and mngmt of a
pt
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27. 9/8/2022 27

28. Cont,
Advantages viscoelastic testing
Short turnaround time
Can detect hyperfibrinolysis
Assess all phases of coagulation
Can be performed at the patients own
temperature
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29. Cont,
Bleeding will be called major if:
Result in drop of Hbn by>=2g/dl
Requires blood transfusion(>= 2u PRBC)
Bleeding into critical closed spaces
Bleeding that require surgical intervention
In general a bleeding resulting in
hemodynamic instability is major bleeding
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30. Definition of massive blood transfusion
Adult
Transfusion of >=10u of PRBC or
TBV over 24 hrs
>50% of TBV within 3hrs
>=4u PRBC within 1hr
>=4u of any components within
30 minutes
Transfusion support to loss of blood
>150ml/min
Pediatrics
Transfusion of >100% of
TBV over 24hrs
>50 TBV within 3hrs
Transfusion support to loss
of blood >10% of TBV/min
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31. Cont,
Indications
Trauma
Surgery
Cardiovascular
hepatic surgery
Obstetric hemorrhages
GI bleeding with liver diseases
Contraindications
no absolute contraindications for MT .
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32. Activate MTP if one or more of
the f/f:
1
• ABC score of two or more
2
• Persistent hemodynamic instability or
blood transfusion in the trauma bay
3
• Active bleeding requiring operation or
angioembolization
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33. Cont,
Assessment of blood consumption(ABC) score
Pulse rate>120bpm
SBP<90mmHg
Positive FAST scan
Penetrating injury to the Torso
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34. Cont,
Revised assessment of bleeding and
transfusion(RABT) score
Penetrating truncal trauma
Shock index>=1
Positive FAST
Pelvic fracture
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35. Cont,
If MT triggers are met:
 Begin universal blood product infusion rather
than crystalloid or colloid solutions
Transfuse RBC and plasma in a ratio between 1:1
and 1:2 (plasma to RBC)
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36. APPROACH TO VOLUME AND BLOOD
REPLACEMENT
requires careful and ongoing consideration of
complex physiologic relationships.
Priorities in MBT
Restoring blood volume and thereby improving
tissue perfusion and oxygenation
Secure hemostasis
Arrest any source of active bleeding
Treat coagulopathy with blood components
Correct hypothermia and acidosis
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37. Crystalloid versus blood products
Correction of a deficit in blood volume with
crystalloids and volume expanders works well for
most mildly and moderately ill or injured patients.
However, large volume resuscitation with
crystalloid alone in severe trauma with massive
blood loss can lead to
 dilutional coagulopathy
severe tissue edema
stiff lungs and abdominal compartment syndrome.
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38. Cont,
For more severely injured or massively
bleeding patients, there has been a shift to:
Early use of blood components for volume
resuscitation
 with avoidance of aggressive crystalloid
resuscitation.
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39. Whole blood vs components
 there is strong evidence from medical &
military experience demonstrating positive
outcomes when fresh WB is transfused to
trauma patients.
And transfusing with fresh WB would seem
ideal but the time required to conduct safety
tests on blood is long
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40. Ratio of component transfusion
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41. Cont,
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42. Key principles of management of
hemorrhage
• Control compressible active bleeding
1
• Minimize the use of intravenous IV fluid
2
• Transfuse as soon as the need is recognized
3
• Apply balanced component transfusion/use Whole blood
4
• Mobilize resources needed & apply point of care coagulation
assessment
5
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43. Cont,
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44. Massive transfusion protocol
Many institutions have created protocols for
massive transfusion using knowledge from
interprofessional teams.
Which facilitate ordering blood products and
receiving them expeditiously from the blood bank.
While these protocols vary between institutions,
many MTP focus on delivering PRBCs in addition
to plt and FFP.
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45. Cont,
Led to the concept of mimicking whole blood
during massive transfusion
still controversial regarding the best ratio
Many experts & studies advocate for a 1:1:1
ratio of FFP, platelets, and PRBCs.
The use of cryopr, fibrinogen conc., and rFVIIIa
have been used with mixed results.
Incorporation of TXA into MTP?
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49. 9/8/2022 49

50. Other haemostatic strategies
Activated factor VII:
The role is unclear.
can be considered as a rescue therapy in patients with
life-threatening bleeding that is unresponsive to
standard haemostatic therapy.
with dose is 35-70 μg/kg
 Antifibrinolytic agents:
useful in bleeding complicated by fibrinolysis such as
cardiac surgery, prostatectomy
Early administration of TXA in bleeding Pts has been
shown to significantly reduce mortality
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51. Cont,
Early use of tranexamic acid in severely
bleeding pts reduce mortality and cost
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52. Cont,
Autologous Blood transfusion:
First gained popularity because of the rising
risk of transfusion-transmitted viral infections.
 Includes :
a) preoperative autologous blood donation (PAD)
b) acute normovolemic hemodilution (ANH)
c) perioperative blood cell salvage
 useful in unanticipated blood loss and in pts with rare BGs.
 generally reserved for massive blood loss in OR
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53. Cont,
Targets of massive transfusion
• Mean arterial pressure (MAP) of >60 mm Hg
and SBP:80-100mmHg
• INR less than 1.5
• aPTT<1.5* normal value
• Hemoglobin 7 to 9 g/dL
• Fibrinogen greater than 1.5 to 2 g/L
• pH 7.35 to 7.45
• Platelets greater than 50K
• Core temperature greater than 35 C
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54. Pediatric MT
Limited data is available for pediatric MT
In majority of the institution a single MT protocol
is used for adult and paediatric
Balanced component transfusion is yet the choice,
Whole blood transfusion?
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55. Obstetric hemorrhage
Pregnancy and the postpartum period are
hypercoagulable states with compensatory
increased fibrinolysis.
When vascular disruption leads to massive
bleeding, those with low fibrinogen are at
increased risk for bleeding.
Most guidelines supports to maintain fibrinogen
≥200 mg/dL .
use of a 1:1:1 ratio for treating massive
hemorrhage in obstetric patients is suggested.
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56. Liver disease
Liver disease
reduced production of coagulation factors and
dysfunctional v.t K-dependent factors and fibrinog.
 reduced hepatic clearance of activation fragments
 In patients with severe liver disease and active
hemorrhage, attempts to normalize platelet
number and plasma coagulation factor conc.
1:1:1 ratio of blood component for treating
massive hemorrhage in pts.
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57. Blood Transfusion reactions
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58. Complications of massive transfusions
Non-fatal complications have been seen in more
than 50% of pts when more than 5 units of blood
products are transfused
Immediate
 secondary to volume resuscitation
 Inadequate resuscitation
Overzealous resuscitation
Dilutional problems:
Problems related to transfusion of large volume of
stored blood
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59. Cont,
Late complications
Transfusion related acute lung injury (TRALI)
SIRS, Sepsis,Thrombotic complication
Generally Specific complications to MT
Metabolic
Hemostatic
Hypothermia
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60. Metabolic complications
Citrate toxicity
 normally blood is anticoagulated with sodium
citrate and citric acid
Each 450 ml of blood contain 9mmol of citrate(too
much in the setting of MT)
Infusion of citrate can lead clinically significant fall
of ionized Ca
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61. Cont,
The liver metabilize 3gm of citrate every 5min
infusion of more than 1 unit of blood every 5
minutes can lead to decreasing ionized Ca2+
levels.
So risks for citrate toxicity increases in two
situations:
Rapid infusion of blood products
Impaired or immature liver functions
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62. Cont,
Ca is important for coagulation, platlet fun and
cardiac and smooth muscle activity
50% of hospital admissions and & 70-100% of
trauma patients have already low Ca(even before
transfusion)
And MT will worsen hypocalcemia thereby
dysrhythmia and hypotension
RXs: for those with hypocalcemia with
symptoms/ECG changes, for MT suppl, ionized
Ca<0.9mmol/L
With Cacl/Calcium gluconate
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63. Cont,
 Hypomagnesemia
 Due to infusion of magnesium poor fluid and high citrate content
during MT
 Hyperkalemia
 Due to hemolysis of RBCS and transfusion of RBCs of long storage
duration, infused through central access and at high speeds
 hyperkalemia results from high-volume transfusion, especially
when infusion rates exceed 100 to 150 mL/min.
 Neonates and pts with underlying cardiac and renal disease are prone
 Prevention:
• Use younger & washed RBCs
• Treatment based on the level
 Hypokalemia
 Due to entry to the transfused RBC
 the alkalosis
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64. Cont,
 Metabolic alkalosis
 Due to citrate overload
 Each unit of blood can generate a total of 23 mEq of bicarbonate
 This can result in a metabolic alkalosis if impaired kidneys fun.
 Acidosis
 Hypoperfusion and liver diseases risks
 Patients requiring a massive transfusion are often acidotic even
before transfusion begins.
 Prolonged states of hypoperfusion lead to acidosis.
 Once acidosis has set in, it further interferes with coagulation by
reducing the assembly of coagulation factors.
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65. .
Days of storage
0 7 14 21 35
% of viable cells 24 hours posttransfusion 100 98 85 80 79
Plasma pH at 37°C 7.20 7.00 6.89 6.84 6.80
2,3 DPG (% initial value) 100 99 80 44 <10
P50 (oxygen affinity) 23.5 23 20 17
Plasma Na+ 168 166 163 156 155
Plasma K+ 4.2 11.9 17.2 21 27.3
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66. Cont,
Hypothermia
Many patients with acute blood-loss susceptible
to hypothermia.
Infusion of cold fluid and blood products, wide
opening of body cavities, decreased heat
production and impaired thermal control
Lower ambient temperatures can further
exacerbate it
Infants and neonates are vulnerable
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67. Cont,
Transfusion of 6u of blood at a T0 of 4C0
reduce body temperature by 1C0
Transfusion of10u cold blood and 1 hr of
surgery leads 3 C0 body tempreture drops
management
Warm room tempreture
Using warm blanket or drapes
Warming iv fluids
High capacity blood warmer
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68. Cont,
Coagulopathy in MT
Due to massive bleeding, coagulation factors are often
being consumed in patients who require massive
transfusion.
 Additionally, dilution of the remaining coagulation
components in addition to hypothermia and acidosis
can lead to coagulopathy and altered hemostasis.
The decreased ability to stop bleeding leads to further
hypothermia and acidosis, creating a positive
feedback loop
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69. 9/8/2022 69

70. cont,
 Plasma(FFP)
 If the PT and/or aPTT are >1.5 times control due to
dilutional coagulopathy, 2 to 8 units of plasma should be
given.
 Each unit of plasma might be expected to increase the
clotting protein levels of 2.5 percent
 Cryoprecipitate/virally inactivated fibrinogen concenc.
 used when fibrinogen levels are critically low (<100 mg/dL)
 Platelets
 4-6u of WB-derived platelets or one apheresis unit should
be given if the platelet count is <50,000/microL.
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71. cont,
Trauma-associated coagulopathy
diagnosed when there is microvascular oozing,
prolongation of the PT and aPTT more than expected by
dilution, significant thrombocytopenia, low fibrinogen
levels, and increased D-dimer levels.
sometimes referred to as traumatic DIC, but it differs from
DIC by:
Is not truly disseminated, not truly intravascular, not truly
coagulation (it is bleeding)
Is effectively treated with antifibrinolytic agents
 No single laboratory test can definitively diagnose or exclude it
 Acidosis and hypothermia can both interfere with the
normal clotting and hemostasis
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72. Cont,
Transfusion related acute lung injury(TRALI)
The mechanism is poorly understood
 incidence of TRALI increases as the number of blood
products given.
rapid onset of hypoxemia within 6 hours of a
transfusion
Patients clinically will look very similar to those with
acute respiratory distress syndrome (ARDS)
Management: stop transfusion & provide supportive
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73. Cont,
Transfusion
associated circulatory
overload (TACO)
 Acute respiratory
distress within 6 hours of
transfusion with features
of left heart failure
including increased CVP
or increased BNP.
 Additional risks in MT
includes pts with CHF,
diuretic dependence,
and renal faillure
 Management: supportive
treatment + diuresis
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74. References
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75. Thank you!
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