BLOOD TRANSFUSION IN ICU

By
Dr.Sherif Badrawy
Critical Care Registrar

HISTORY OF TRANSFUSION
Important dates:
1665: first recorded transfusion; between dogs
In 1667, blood transfusron from sheep to male
1795 first human-to-human transfusion
1901. description of blood groups
World War 1: development of blood banks
1960s-1970s: methods to separate whole blood,
prevent
antibody formation, and detect infections

EVOLUTION OF TRANSFUSION

SOME FACTS ABOUT BLOOD

TRANSFUSION
Only absolute indication is to increase oxygen delivery
to Tissues in anaemic patients- to increase oxygen
carrying capacity.
It is a tissue transplantation procedure
Blood should not be used for intravascular volume
expansion

BLOOD TRANSFUSION

FACTORS THAT MAY RESULT IN A PATIENT BEING

POTENTIALLY CLOSER TO THE CRITICAL POINT
THAN NORMAL

Reduced oxygen delivery.

(a) Decreased cardiac output:
(i) Pre-morbid disease e.g.,IHD, valvular heart disease.
(ii) Hypovolaemia e.g., increased capillary leak.
(iii) Arrhythmias e.g., atrial fibrillation.
(iv) Pulmonary embolism.
(v) Specific heart muscle disease e.g., systemic inflammatory
response syndrome (SIRS) related cardiomyopathy.

(b) Hypoxaemia secondary to acute

respiratory failure.-(ALI)/ (ARDS).

FACTORS THAT MAY RESULT IN A PATIENT BEING

POTENTIALLY CLOSER TO THE CRITICAL POINT
THAN NORMAL
Increased oxygen consumption
Pain, stress, anxiety.
Shivering.
Fever.
Severe infection.
Sepsis/(SIRS).
Trauma

Surgery.
Burns.
Adrenergic drug infusions.
Work of breathing e.g., during weaning.
Convulsions.

Anemia VS blood transfusion

in ICU

 Anemia Frequency

>60% of ICU patients upon admission

90% of ICU patients by day 3 in ICU
97% of ICU patients by day 8
Thomas J, Jensen L, Nahirniak S, Gibney RT. Anemia and blood transfusion practices in
the critically ill: a prospective cohort review. Heart Lung. 2010;39(3):217-225.

3a

 Anemia morbidity and mortality

Associated with increased 90-day mortality in patients
with chronic obstructive pulmonary disease
Associated with adverse outcomes in patients with
congestive heart failure, acute myocardial infarction,
and chronic kidney disease

Rasmussen L, Christensen S, Lenler-Petersen P, Johnsen SP.Anemia and 90-day mortality

3b
in COPD patients requiring invasive mechanical ventilation. Clin Epidemiol. 2011;3:1-5.

 Anemia Cost
Associated with >twice inpatient costs in patients with
chronic conditions
Associated with increased length of stay in patients
with heart failure

Nissenson AR, Wade S, Goodnough T, Knight K, Dubois RW. Economic burden of

anemia in an insured population. J Manag Care Pharm. 2005;11(7):565-574.

4a

 Blood transfusion Frequency

20% to 62% of ICU patients receive 1 or more units
of blood

Taylor RW, O'Brien J, Trottier SJ, et al. Red blood cell transfusions and nosocomial
infections in critically ill patients. Crit Care Med. 2006;34(9):2302-2308.

4b

 Blood transfusion morbidity and mortality

Associated with as much as a 40% increase in 30-day
morbidity Associated with as much as a 38% increase in 30-day
mortality

Bernard AC, Davenport DL, Chang PK, Vaughan TB, ZwischenbergerJB. Intraoperative transfusion of 1 U to 2 U packed
red blood cells is associated with increased 30-day mortality, surgical- site infection, pneumonia, and sepsis in general
surgery patients. J Am Coll Surg. 2009;208(5):931-937.

 Blood transfusion Cost

Associated with around 2 day increase in length of stay per
transfusion

Hill SR, Carless PA, Henry DA, et al. Transfusion thresholds and other strategies for guiding allogeneic
red blood cell transfusion. Cochrane Database Syst Rev. 2002(2):CD002042.

DOES OLD BLOOD IMPROVE

OXYGEN CONTENT?

STORAGE DEFECTS AND MICROVASCULAR

PERFUSION

Decreased 2,3DPG, ADP,NO

Build-up of
cytokines, Free
Hb, K+, debris
Poor deformability

Will they improve

oxygen content and
delivery ?
Immune
suppression

Clinical and animal studies report contradictory findings about the

oxygenation capacity of

Infections

stored RBCs

TRANSFUSION TRIGGER
Risk
Risk of
of low
low hemoglobin
hemoglobin
Risk of
of blood
blood transfusion
transfusion Risk

Acceptable hemoglobin concentration

TRANSFUSION TRIGGER CONTROVERSY

10/30?

8/24?
7/21?
Transfusion paradigms

Transfusion trigger:
hemoglobin or
hematocrit level
below which a blood
transfusion was to be
given. Most trials
compared outcomes
in patients
transfused at Hgb
thresholds between
7 and 10g/dL

TRANSFUSION LITERATURE
The current paradigm of the transfusion trigger of Hb 7
g/dL comes from the TRICC trial
It challenged the solid belief that high hemoglobin
values are safe, effective, and necessary in the critically
ill.
It triggered a more focused look at the physiology of
oxygen transport in the context of haemoglobin
availability
It raised the question of whether transfusion has
problems in its own right

TRANSFUSION TRIGGERS IN NON-BLEEDING

PATIENTS

STUDY DESIGN
The patients included were >16 years old, critically ill,
normovolaemic, non-bleeding, Hb <90 within 72 h of ICU
admission

MC RCT involving 25 centers over 3 years with n = 838

The comparison groups had different Hb target ranges these

were restrictive (70-90g/L) vs liberal groups (100-120g/L), with
the lower value as the transfusion threshold

FINDINGS
no difference in the the primary endpoint of mortality @ 30 days
increased complications in liberal strategy group
significant reduction in blood exposure in the more restrictive
group
significantly lower in-hospital mortality in the less sick (APACHE
20 OR LESS: 8.7 percent in the
restrictive-strategy group and 16.1 percent in the liberal-strategy
group, p = 0.03) and those aged <55y
in the restrictive transfusion strategy group

 The mortality rate during hospitalization was significantly

lower in the restrictive-strategy group (22.2 percent vs.
28.1 percent, p = 0.05).

trend to decreased survival with a restrictive strategy for

patients with cardiovascular disease
no differences in duration of MV or ventilator free days

QUESTIONS UNANSWERED IN TRICC

TRIAL
? Why liberal strategy group failed to improve mortality &
rates of organ failure in critically ill ??
Possible explanations :
a) greater no. of allogenic RBC units depressed
host immune responses.
[Hermans j et al circulation 1998]
b) altered microcirculatory flow as consequence
of prolonged storage times.

 A CANADIAN PAEDIATRIC STUDY

MIRRORED THE FINDINGS OF TRICC, BUT
WITH MODS AS THE PRIMARY OUTCOME

CURRENT GUIDELINES ON TRANSFUSION IN

SEPSIS

Maintain a haematocrit of > 30% in the presence of hypoperfusion in the

first 6 hours
Once tissue hypoperfusion has resolved and in the absence of extenuating
circumstances, such as myocardial ischemia, severe hypoxemia, acute
hemorrhage, or ischemic coronary artery disease, we recommend that red
blood cell transfusion occur when the hemoglobin concentration decreases to
< 7.0 g/dL to target a hemoglobin concentration of 7.0 to 9.0 g/dL in adults
Surviving Sepsis Campaign

TRANSFUSION REQUIREMENTS IN SEPTIC

SHOCK (TRISS)TRIAL
trial to evaluate the effects on mortality of leuko
reduced blood transfusion at a lower versus a higher
hemoglobin threshold among patients with septic
shock who are in the (ICU).
multicenter, parallel-group trial
when the hemoglobin level was 7 g /dl or less (lower
threshold) or when the level was 9 g /dl or less (higher
threshold) during the ICU stay. Pt receives 1 unit of
leuko reduced red cells

TRANSFUSION REQUIREMENTS IN SEPTIC

SHOCK (TRISS)TRIAL
Primary outcome- Death at 90 days post randomisation

A significant difference in mortality was not

found
43% in the lower threshold group
45% in the higher threshold group

There were no differences in ischemic events, duration

of vasopressor or mechanical ventilation, and length of
stay

TRANSFUSION REQUIREMENTS IN SEPTIC

SHOCK (TRISS)TRIAL
CONCLUSIONS: Among patients with septic shock,
mortality at 90 days and rates of ischemic events and
use of life support were similar among those assigned
to blood transfusion at a higher hemoglobin threshold
and those assigned to blood transfusion at a lower
threshold; the latter group received fewer transfusions

 Six-month mortality rates were higher in patients

receiving transfusion (28.1% vs 11.7%)
protective effect of transfusion in patients with nadir
hemoglobin < or =8 g/dL
transfusion was associated with increased mortality in
patients with nadir hemoglobin > 8 g/dL

 RCT with n = 502

HCT 30% vs HCT > 24%
no difference in mortality and severe morbidity
number of RBCs transfused was an independent risk
factor for clinical complications

TRANSFUSION TRIGGERS IN BLEEDING

PATIENTS

OUTCOMES
primary outcome was mortality at 45 days: 5% vs. 9%
in favour of restrictive approach
other secondary outcomes: further bleeding associated
with hemodynamic instability or Hgb drop 2
within 6 hours, number of RBCs transfused, cardiac
complications, transfusion reactions and mean LOS

COMMENTARY AND CRITICISMS

Patients with major haemorrhage or low rebleeding risk were
excluded
Patients had emergency upper GI endoscopy within a mean of 5
hours of admission unrealistic in most clinical settings
Subgroup analysis suggested benefit extends beyond those with
portal hypertension
the liberal arm may have benefited from hemostatic
resuscitation rather than simply RBC transfusion which may
cause dilutional coagulopathy

HARM FROM BLOOD TRANSFUSION

Conclusion
Blood transfusion is an independent risk factor for:
morbidity and mortality
ICU admission
Hospital LOS
Increased cost

 Sepsis Occurrence in Acutely Ill Patients study

was a multicenter, observational study followed
up to 60 days
Transfused patients were sicker and did worse,
but blood transfusion was not significantly
associated with death in multivariate analysis in
fact the opposite was found.

Massive Transfusion

MASSIVE TRANSFUSION
Settings

Trauma
Obstetric
Surgical

MASSIVE TRANSFUSION
Definitions
Replacement of one blood volume in a 24 hour period
Transfusion of >10 units RCC in 24 hours
Transfusion of 4 or more RCC within 1 hour when
ongoing need is foreseeable
Replacement of >50% of the total blood volume within
3 hours

BLOODY VICIOUS CYCLE

MASSIVE TRANSFUSION
Now recognised DIC is a significant contribution: loss
of localisation microvascular damage
depletion of coagulation factors
In the massively transfused patient, platelets and
impaired platelet function are the most consistent
significant haematological abnormalities. Factor
deficiency is initially confined to factors V and VIII

T SOME HELP.
Contact Key Personnel
surgeon/ obstetrician
Blood Bank
Haematologist
Shock/hypoperfusion is the key underlying problem fix
it!
Control bleeding:
Early surgery (vs pre-op stabilisation)

BLOOD TRANSFUSION RISKS

EARLY
TACO (transfusion associated circulatory overload)
TRALI (transfusion related acute lung injury)
haemolytic reactions (incompatibility ABO, Rh)
fever
allergy (mild -> anaphylaxis)
infection: bacterial contamination
air embolism
hypothermia

BLOOD TRANSFUSION RISKS

LATE
viral infection: hepatitis B (~1 in 750,000), HIV (<1 in a million), CMV
bacterial infection: Treponema pallidum, Salmonella, Yersinia,
Pseudomonas, Staphylococcus spp
parasitic infection: malaria (<1 in a million), toxoplasmosis, prion infection
GVHD (graft versus host disease)
immune sensitisation
TRIM (transfusion-related immunomodulation); leading to increased risk of:
infection, tumour
recurrence, activation of latent viral infections, recurrent miscarriages

TRALI

TRALI
hypoxia and bilateral pulmonary edema occurring during or within 6 h of
a transfusion in the absence of other causes such as cardiac failure or
intravascular volume overload
incidence is 1 in 5,000 U of plasma containing products (FFP, platelets
or whole blood)
Theories
(1) donor anti-granulocytic antibodies called leukoagglutinins in plasma
target recipient leucocyte antigens on neutrophils sequestered in the
lungs, resulting in an immune reaction
(2) biological response modifiers (BRMs) such as cytokines and
biologically active lipids (e.g. in aged cellular components) cause a lungmediated response

 MANAGEMENT OF TRALI
stop transfusion
respiratory support (may require NIV or intubation)
lung protective ventilation if intubated
haemodynamic support if needed e.g. noradrenaline
supportive care and monitoring
no evidence for steroids
inform blood bank and haematology

 PROGNOSIS OF TRALI
most recover within 48-96 hours
radiological changes often last 7 days
mortality 5%
PREVENTION of TRALI
limit transfusion of blood products
avoid donations (especially FFP) from multiparous women

TRANSFUSION OF OTHER BLOOD

PRODUCTS
Transfusion of platelets

Prophylaxis:
< 10 without associated risk or < 20 with additional risk factors
Keep > 50 in patients undergoing surgery or invasive procedures
< 50 in massive haemorrhage and < 100 in diffuse microvascular bleeding

Not appropriate if:

Thrombocytopenia is due to immune mediated destruction
In TTP and HUS except if continuous bleeding
In uncomplicated cardiac bypass surgery

TRANSFUSION OF OTHER BLOOD

PRODUCTS
Transfusion of Fresh frozen plasma
FFP has an INR of ~1.6 -> cannot lower below INR 1.7
FFP must be ABO compatible
10-20 cc/kg (4-6 units in adults) will increase factors by ~20%
FFP contains all coagulation factors in normal concentrations.
Rh factor need not be considered
there are no viable leukocytes so plasma does not carry a risk of CMV
transmission or GVHD

TRANSFUSION OF OTHER BLOOD PRODUCTS

Indications of Fresh frozen plasma
documented coagulation factor deficiencies and active bleeding, or
who are about to undergo an invasive procedure.
Deficiencies may be congenital or acquired secondary to liver
disease, warfarin anticoagulation,DIC.
Recombinant or Factor VIII concentrates should be used to replace
Factor VIII.
Reversal of warfarin anticoagulation with plasma is indicated only if
significant bleeding or risk is present.
Rapid reversal for life threatening bleeding may be achieved with
recombinant Factor VIIa (Novo7)

FACTOR VIIA
recombinant protein
MECHANISM OF ACTION tissue factor + VIIa +
platelets -> platelet aggregation
production of platelet-fibrin matrix haemostasis
used in massive transfusion senarios to attempt to
control intractable haemorrhage
expensive
need platelets for rFVIIa to be effective

EVIDENCE OF FACTOR VIIA

initially developed for haemophilia
encouraging case reports from use in trauma
may avoid problems with ongoing transfusion disease
transmission, acute lung injury, TRALI, hypothermia, acid-base
disturbance, volume overload
probable publication bias -> tendency to publish cases where it
has produced successful results
massive transfusion and trauma -> off licence use

 Multicentre RCT
n = 399 with acute intracerebral haemorrhage
single IV injection of recombinant factor VIIa (40, 80 or 160mcg/kg)
VS placebo within 1 hour of their base line CT head scan.
-> significant reduction in volume of haematoma on CT @ 24 hours
with therapy proportional to dose.
-> significant reduction in 30 day mortality without increase in
severely disabled patients.
-> no statistically significant increase in thromboembolic events
although there was a trend

TYPES OF RBC PRODUCTS

WHOLE BLOOD : RBC+platelets+plasma proteins
- indicated in hemorrhage & anemia
- autologous donation prior to surgery
PACKED RBCS : 200ml of RBCS + preservatives
- each bag has Hct of 60% & approx
200 mg elemental iron.
GAMMA IRRADIATED : destruction of donor T-lym.
for GVHD prevention in immunocom.,
stem cell recepient.

- CMV antibody neg : used in transplant & pregnancy(high risk of

CMV complications)

- Leukocyte depleted : in febrile reactions,to avoid leucocyte

immunization in hema tological malignancy.
- Washed RBCS : washed with NS to remove donor serum,
-used in IgA def & those at high risk for
anaphylaxis,
- in PNH pt ( to deplete complement)

GRANULOCYTES
- Used in profound & prolonged neutropenia secondary to
marrow suppression.
- Collected by : 1) filtration leukapheresis
-

2) continuous flow centrifugation

- Usefulness is doubted d/t :

1) inability to collect sufficient cells
2) early development of allo-immuniz.

CRYOPRECIPITATE
contains fibrinogen,v-Wfactor,VIII,XIII,fibronectin,
- conc. of fibrinogen in cryo > 10 times of FFP
Indications : 1) DIC, along with FFP
2) isolated
hypofibrinogenemia(<100mg/dl)
3) platelet dysfunction not
responding
to DDAVP/dialysis.
Dose : ~ one bag / 10 kg body weight

ANTI-THROMBIN CONCENTRATES :
- used in anti-thrombin deficiency
thrombophilia
GAMMA-GLOBULINS :
- in hypogammaglobulinemia,
- in high doses in autoimmune diseases
- SPECIFIC IMMUNOGLOBULINS :
- for prophylaxis in rhesus,tetanus,zoster,
Hep B.

CRASH-2 TRIAL : EFFECT OF TRANEXAMIC ACID ON

DEATH,VASC. OCCLUSIVE EVENTS & BLOOD
TRANSFUSION IN TRAUMA PATIENTS.
- Early administration of tranexamic acid,an antifibrinolytic agent,to trauma
patients,with or at risk of significant bleeding reduces the risk of death from
hemorrhage with no apparent increase in fatal or non-fatal vascular occlusive
events.(with no stastically significant difference in transfusion requirements)

- DOSAGE : 1gm loading dose in 10 mins f/b infusion of 1gm over 8hrs.
[lancet- 2010]