Blood Transfusion and Transfusion Reactions: Life Threatening Process

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BLOOD TRANSFUSION

AND TRANSFUSION
REACTIONS
Life Saving

Life Threatening Process


LEARNING
OUTCOMES
Atthe e n d of this topic, you should able to:
• Understand concept of Whole blood and blood components
• Discuss types and indications of blood transfusion
• Enlist tests tu b e performed prior to blood transfusion
• Understand transfusion reactions and their managements.
Blood Transfusion
• Proce ss of transfe rrin g b lood-b ase d p roducts from on e p e rson into the
circulatory system of another through an intravenous line.
• The appropriate use of blood means the transfusion of safe blood products only to treat a
condition leading to significant morbidity or mortality that cannot b e prevented or managed
effectively by other means.
• Transfusion carries the risk of adverse reactions and transfusion- transmitted infection.
Plasma can transmit most of the infections present in whole blood and there are very few
indications for its
PURPOSE OFBLOOD
TRANSFUSION THERAPY
* REPLACEMENT
* THERAPEUTIC
1.To restore intravascular volume with whole blood or albumin.
2.To restore the oxygen capacity of blood by replacing red blood
cells.
3.To replace clotting factor and correction of anemia
Blood safety
 transfusion-transmissible infection
 window period : is the period during the development of a new infection i n a previously non-infected person i n
which the person’s blood may b e very infectious, but the detectable antibody has not yet appeared.

WHOLE BLOOD AND BLOOD


COMPONENTS
• 350ml /450 ml of blood is collected from a donor into a plastic bag containing an
anticoagulant
• This is called 1 “unit” of whole blood

• Types of blood components:-


• R e d blood cell concentrate (packed red blood cells)
• Platelet concentrate
• Fresh frozen plasma
• Cryoprecipitate
Plasma or platelets collected by apheresis.
Apheresis: a method of collecting plasma or platelets directly from the donor, usually
by a mechanical met hod
Platelets 2nd centrifugation Platelets
rich concentrate
WWhh plasma
oollee
bbllooo
odd FFP for
clinical use
1
s Red
t Fresh plasma FFP for
fractionation
c Cell
e concent
n Optimal additive rate Cryoprecipitate
t solution
r
i
f
u
Red cells
g in
OAS a
t Dr. Salwa Hindawi
Effects of storage on whole blood
■ Reduction i n the p H (blood b e c o m e s m o r e acidic)
■ Rise i n plasma potassium concentration (extracellular K+)
■ Progressive reduction i n the red cell content of 2,3 diphosphoglycerate (2,3 DPG) which may reduce the release of oxygen attissue level until 2,3 DPG is restored
■ Loss of alplatelet function i n whole blood within 48 hours of donation
■ Reduction i n Factor VIII to10–20% of normal within 48 hours of donation. Coagulation factors such as VII and IX are relatively stable i n storage

TYPES OF BLOOD
TRANSFUSION
• FRESH BLOOD TRANSFUSION
Blood less than 24 hours old from the time of collection

• AUTOLOGOUS TRANSFUSION
Blood collected from a patient for re-transfusion at a later time into the same individual

• MASSIVE TRANSFUSION
N u m b e r of units transfused in a 24 hours period exceeds the recipient’s blood volume

• MULTIPLE TRANSFUSION
Repeated transfusion of blood over a long period of time (months or year)
INDICATIONS OF BLOOD
TRANSFUSION
• Whole Blood:
Storage -4° for up to 35 days
• Acute blood loss (trauma )
• Shock
• Exchange transfusion in neonate
• Considerations
• Use filter as platelets and coagulation factors will not b e active after 3-5 days
• Packed red blood cells:
Storage -2– 6O C
• Chronic severe Anemia
• Leukemia
• Thalassemia
• Platelets concentrate:
Platelet viability is optimal at 22° C but storage is limited to
4-5 days .
1 unit/10 kg of body weight increases Plt count by 50,000
• Thrombocytopenia <15,000
• Bleeding due to platelet dysfunction
• Malignancy
• Major surgery
• Fresh frozen plasma:
Storage FFP-12 months at –18 degrees or colder
• Liver disorders
• DIC
• Coagulation
factor
deficiency (V,
VII)
Cryoprecipitate:
Descriptio
n
Precipit
ate
formed/
collecte
d when
FFP is
thawed
at 4°
Storage
After
collectio
n,
refroze
n and
PRE-TRANSFUSION
TESTING
• ABO and Rh (D) blood
grouping :
• Patient’s and donor’s blood sample

• Cross matching
• Major of blood
cross match- sample:
Pt’s serum + Donor cells
• Minor cross match- pt’s cells + Donor serum
BLOOD
GROUPING
PRE-TRANSFUSION TESTING
• Screening
(contd.) for Transfusion transmitted diseases
(Donor Sample)
HIV 1 and
2 HBsAg
HCV AIDS
Treponema Hepatitis
pallidum B
Plasmodium Hepatitis C
species Syphilis
Malaria
Transfusion Reactions
• Infectious
• Viral
CAUSES OF TRANSFUSION
• Bacterial REACTIONS
• Clerical errors:
• Inadequate labeling
• Noninfectious • Wrong blood issued
• Reaction to RBC • Technical errors:
Antigens
• Acute Hemolytic Transfusion Reactions (AHTR) • Error in blood grouping & cross matching
• Incorrect interpretation of test results
• Delayed Hemolytic Transfusion Reactions
• Reactions
(DHTR)to Donor • Others:
• Blood contamination during phlebotomy
Proteins
• Minor Allergic Reactions • Blood infusion thr’ small bore needle
• Anaphylactic Reactions • Blood cooler to -30⁰C or warmed to > 42⁰ C
• White Cell-Related Transfusion • Concomitant administration blood & drugs thr’ c o m m o n set
Reactions
• Febrile Reactions
• Transfusion-Related Acute Lung Injury (TRALI)
How to Prevent Errors in the Transfusion Chain

 Where in the process do errors occur?

Sample Error Technical Error

Wrong
Storage Error
Blood
Issued
Patient Administrativ
Misidentificatio e Error
n

 Who is making the errors?

 Why are the errors occuring – which elements of good transfusion practice are failing
CLASSIFICATION

Transfusion reaction

acute delayed

Immunologic Non Immunologic Non i m m unologic


immunologic
Acute Transfusion Reactions
• Hemolytic Reactions (AHTR)
• Febrile Reactions (FNHTR)
• Allergic Reactions
• TRALI(Transfusion related acute lung injury)
• Coagulopathy with Massive transfusions
• Bacteremia
Febrile (non haemolytic) Transfusion Reaction
(FNHTR)
 Rise i n patient temperature >1°C (associated with transfusion without other fever precipitating factors

 On se t d uring or with in 4 hours following tran sfusion ,Re action induced by cytokines.

 Occurs with approx 1% of PRBC transfusions and approx 20% of Plt transfusions

Mild: unexplained fever ≥38°C and a temperature rise of at least 1°C but <1.5°C from pre-transfusion baseline,
occurring in the absence of chills, rigors, respiratory distress and hemodynamics instability
• Moderate: unexplained fever ≥38°C and a temperature rise of at least 1°C but not meeting criteria for either mild
or severe FNHTR
Severe: unexplained fever >39°C and a temperature rise ≥2.0°C from pre-transfusion baseline and chills/rigors .
• STOP TRANSFUSION
• Check label and recipient identity

•  Slow the transfusion if reaction is mild and MO elects to continue transfusion


•  Antipyretic Paracetamol 1g po and monitor closely
•  Steroids are not appropriate treatment for minor reactions
Acute Hemolytic Transfusion Reactions
(AHTR)
• Occurs when incompatible RBC’s are transfused into a recipient who has pre- formed antibodies (usually ABO or
Rh)
• Antibodies activate the complement system, causing intravascular hemolysis
• Symptoms occur within minutes of starting the transfusion
• This hemolytic reaction can occur with as little as 1-2 cc of RBC’s
• Labeling error is most common problem
• Can be fatal
• Fever , Chills, rigors
Signs and


Nausea and vomiting
Hypotension and tachycardia (bradykinin) Symptoms
• Flushed and dyspneic (histamine)
• Chest, abdominal or low back pain (cytokine release)
• Headache
• Hemoglobinemia and hemoglobinuria 
• Oliguria with dark urine or anuria Pallor, jaundice - Bleeding (due to DIC) Stop transfusion
• Check label and recipient identify
• Replace IV set and start normal saline

• Treat shock and maintain blood pressure with IV saline infusion

• Investigate possible DIC and treat if clinically significant bleeding


• Diuretic, eg Frusemide 1-2 mg/kg IV and/or Mannitol, may help maintain urine flow
Hydrocortisone may b e considered

Samples to assess renal and liver function, DIC and hemolysis, e.g full blood count, unconjugated bilirubin, LDH and haptoglobin
Send Hemovigilance notification to Blood Bank
Delayed Hemolytic Transfusion Reactions
• Onset usually 1-7 days post transfusion but may b e up to 28 days.
• Worsening anaemia and jaundice from destruction of red cells
 Often asymptomatic but rarely splenomegaly, haemoglobinaemia and
haemoglobinuria .
• Renal impairment may occur in severe cases
Investigate haemolysis:
 Full blood count with film comment
 direct antiglobulin test (may b e negative when most red cells cleared)
 Blood group antibody screen (may b e negative until red cells cleared)
 Liver function tests
 Haptoglobin concentration falls while haemolysis is occurring
Allergic Transfusion
Reactions
Allergic Reaction (minor)
Frequency: 1:100 - 1:500 More c o m m o n with Plasma and Platelet Components .
Onset: from c o m m e n c e m e n t to 4 hours after transfusion
 Recipient may have an antibody reacting with an antigen i n the transfused product .
Minor or localised reaction:
 Flushed skin  Morbilliform rash with itching
 Urticaria (hives)  Angioedema
 Periorbital itch, erythema and o e d e m a  Conjunctival o e d e m a
 Minor o e d e m a of lips, tongue and uvula
Management
 Slow transfusion
 Check label and recipient identity
 Antihistamine, e g Loratadine 10mg or Cetirizine 10mg po if symptoms are troublesome
 If symptoms mild and transient, transfusion may r e s u m e
 Continue transfusion ata slower rate with increased monitoring, e g BP/TPR 15 – 30min
 Send Haemovigilance notification toBlood Bank
 If symptoms increase treat asa moderate or severe reaction
Allergic Reaction (moderate)
Frequency: 1:500–1:5,000

 Onset usually within first 50-100 m L infused and within 4 hours of transfusion .
Moderate or widespread reaction:
 Symptoms as for minor reactions, and –
 Cough
 Hypotension and tachycardia
 Dyspnoea and oxygen desaturation are c o m m o n
 Chills and rigors
 Loin pain and angina
 Severe anxiety
Management
• Stop transfusion
• Check label and recipient identity
• Replace IV set and give saline to k e e p vein o p e n and/or maintain BP
• Monitor closely and treat symptomatically as required with IV fluids, oxygen and antihistamine, eg Promethazine 25-50 m g IV
(max rate 25 m g / m i n ) or Loratadine 10mg or Cetirizine 10mg po. Hydrocortisone may b e considered
• Send Haemovigilance notification to Blood Bank
• Discuss with TMS promptly if m o d - severe reaction present
Anaphylactic / Anaphylactoid Allergic Reaction (severe)
Frequency: 1:20,000 – 1:50,000

Rapid onset :

-- May
IgA b e due to an antibody in the recipient reacting with a plasma protein in a blood component
- Haptoglobin o Other plasma protein.
Life-threatening reaction:
 Symptoms as for moderate reactions, and
 Severe hypotension, shock and tachycardia
 Widespread urticaria with skin flushing and itching
 Wheezing, stridor, change in voice
 Severe anxiety
Management
 Stop transfusion
 Check label and recipient identity
 Follow Anaphylaxis Guidelines:
• Adrenalin 1:1000 IM and repeat at 5- 10 m i n intervals if required: - Adult: 0.5mg / 0.5 mL - Children
0.01mg/kg IM; m i n dose 0.1mL, max dose 0.5mL
Replace IV set and give rapid IV colloid or saline, eg adults 2 L, children 20 mL/kg, until SBP>90
• m m H g , then titrate
• Consider Hydrocortisone 4mg/kg (200- 400 m g IV)
Consider H1-antihistamine, eg Loratadine or Cetirizine 10 m g po for itch or angioedema.
• H2-antihistamine, eg Ranitidine may b e added for severe reactions. Note: Sedating
• antihistamines,• eg Promethazine contraindicated
 CPAP ventilation, chest X-ray
 ICU liaison
 Discuss severe reactions with TMS
TRALI: Transfusion Associated Lung Injury
• Frequency: <1:5,000
• Onset within 6 hours following transfusion of plasma or plasma-
containing cellular components
• A complex group of disorders indistinguishable clinically from
ARDS
• One recognised mechanism involves a donor antibody reacting
with recipient neutrophil- or HLA-antigens causing cell activation that
results in acute severe microvascular lung injury .
• Onset of severe dyspnoea and cyanosis proceeding to
respiratory failure with bilateral infiltrates on CXR within 6
hours of transfusion .
•Absence of left atrial hypertension (circulatory overload)
Distinguish from:
 cardiovascular overload (TACO) o
other causes of acute respiratory distress syndrome (ARDS)
or less severe acute lung injury (ALI)
Management
- Intensive care management for
respiratory failure
- Diuretics are not usually helpful
TACO: Transfusion Associated
Circulatory Overload
• Rapid onset after infusion of a volume of fluid that is clinically
significant for the affected recipient.
• Main risk factors: premature/ new borne or Elderly patients
recipient with impaired cardiovascular state or renal impairment o
Infusion too rapid for recipient o Volume infused too great, especially
if normovolaemic.
• Clinics: Acute heart failure
Prophylaxis: Slow infusion rate, low volume of transfusion
 Increased blood pressure
 Rapid bounding pulse
Respiratory distress with raised resp. rate, dyspnoea, cough, pink
frothy sputum, crepitations and oxygen desaturation consistent with
pulmonary oedema
 Raised JVP and CVP
 Nausea
 Acute or worsening pulmonary oedema on CXR
Restlessness, anxiety
Management
 Stop transfusion
 Seek urgent
medical assessment

Sit recipient upright with legs over side of bed, administer
oxygen, diuretic (Frusemide 1-2 mg/kg IV), CPAP ventilation.
TRALI versus TACO

Kim et al.
2015.
Bacterial Contamination(Bacterial Sepsis)
• More common and more severe with platelet transfusion (platelets are stored at room
temperature)
• Organisms
• Platelets—Gram (+) organisms, ie Staph/Strep
• RBC’s—Yersinia, enterobacter
Symptoms :
- Rigor, chills, fever
-Shock, usually within minutes of starting transfusion 
-Respiratory distress, wheezing and oxygen desaturation
-Pain up arm , Chest and back / loin pain Nausea,
Give antibiotics: a broad-spectrum penicillin or cephalosporin and gentamicin
5mg/kg.
Cooling
 Progressive onset during rapid infusion of large
volumes of cold fluids, including blood products (more
than 50 mL/kg/h in adults or 15 mL/kg/h in children.
Signs And Symptoms
• Reduced temperature
• May b e associated with cardiac rhythm irregularity and
a negative inotropic effect
• Impaired platelet function and coagulation
Limit heat loss from the recipient and monitor BP/TPR
 If further blood components required, infuse through a
warmer
Chronic Transfusion Reactions
o Alloimmunization

o Transfusion Associated Graft Verses Host Disease (GVHD)

o Iron Overload

o Transfusion Transmitted Infection

o Post Transfusion Purpura :


(Onset about 5-12 days after transfusion of cellular blood components ,
• Severe thrombocytopenia often with purpura and possibly other
bleeding .
• Thrombocytopenia will persist for 1-2 weeks
Transfusion Related Graft- versus
-Host Disease
General managements of Acute transfusion reactions

• category 1: Mild reactions


• Urticaria and itching are not uncommon reactions following transfusion. They arise as a result of
hypersensitivity with local histamine release to proteins, probably in the donor plasma.
• Signs and symptoms
• Localised cutaneous reactions (urticaria and rash), often accompanied by pruritus (intense itching), occur
within minutes of commencing the transfusion. The symptoms usually subside if the transfusion is slowed
and antihistamine is given .
Management
1- Slow the transfusion.
2 -Give an antihistamine: e.g. chlorpheniramine 0.1 mg/kg by intramuscular injection.
3 Continue the transfusion at the normal rate if there is no progression of symptoms after 30 minutes.
4 If there is no clinical improvement within 30 minutes or if signs and symptoms worsen, treat the reaction as
a Category 2 reaction.
Category 2: Moderately severe reactions

Signs and symptoms usually occur 30–60 minutes after the start of the transfusion.
Signs
■ Flushing ■ Urticaria
■ Rigor ■ Fever
■ Restlessness ■ Tachycardia
Symptoms
■ Anxiety ■ Pruritus (itching)
■ Palpitation ■ Mild dyspnoea
■ Headache
1- Stop the transfusion. Replace the infusion set and k e e p the IV
line open with normal saline.
3- Administer antihistamine IV or IM (e.g. chlorpheniramine
0.01 mg/kg or equivalent) and an oral or rectal antipyretic (e.g.
paracetamol 10 mg/kg: 500 m g – 1 g in adults). Avoid aspirin in
thrombocytopenic patients.
4 Give IV corticosteroids and bronchodilators if there are
anaphylactoid features (e.g. broncospasm, stridor).
5 Collect urine for the next 24 hours for evidence of haemolysis
and send to the laboratory.
6 If there is a clinical improvement, restart the transfusion
slowly with a new unit of blood and observe carefully.
Category 3: Life-threatening
reactions
The most common causes of life-threatening transfusion reactions are:
■ Acute intravascular haemolysis
■ Bacterial contamination and septic shock
■ Fluid overload
■ Anaphylactic shock
■ Transfusion-associated lung injury (TRALI)
Signs
• Rigor
• s
• Fever
• Restle
Shock
• ssness
Tachycardia
• Haemoglobinuria (red
• urine) Unexplained
bleeding (DIC)
Symptoms
■ Anxiety
■ Chest pain
■ Respiratory distress/shortness of breath
■ Loin/back pain
■ Headache
■Dyspnoea
M anagem e
nt
1- Stop the
transfusion
and Check
label and
recipient
identity
- Replace the infusion set and k e e p IV line open with normal
saline. 2- Infuse normal saline to maintain systolic BP (initial 20–30
4 -Give 1:1000 adrenaline 0.01 mg/kg body weight by
intramuscular injection.- Children 0.01mg/kg IM;
m i n dose 0.1mL, max dose 0.5mL
5- Give IV corticosteroids ( Consider iv Hydrocortisone
4mg/kg (200- 400 m g ) and bronchodilators if there
are anaphylactoid features (e.g. broncospasm,
stridor).
6 -Give diuretic: e.g. frusemide 1 mg/kg IV
or equivalent
7- Consider H1-antihistamine, eg Loratadine or
Cetirizine 10 m g po for itch or angioedema.
o H2-antihistamine, eg Ranitidine may b e added
for severe reactions.
Reference
• American Society of Hematology 2021 L Street NW, Suite 900
Washington, DC 20036
• www.hematology.org
• 2012 Clinical Practice Guide on Red Blood Cell Transfusion
• Handbook of Transfusion Medicine. Fourth
Edition. www.transfusionguidelines.org.uk
T h A n k You!
Hope you
learned
something!
Case 1
Mr gulled is a 14 year old male is brought to the ER
after a motor vehicle accident. He is in pain,
tachycardic to 120s, but normotensive.
• Given his acute blood loss, transfusion of 1u PRBC
is initiated (after appropriate type and cross-
matching revealing no antibodies, and compatibility
with donor blood).
• During transfusion, he develops a fever but
otherwise has no new signs or symptoms.
• What is the diagnosis?
Febrile Nonhemolytic
Transfusion Reaction
Case 1 (continued)
• Mr gulled does well following discharge. Fifteen years
later (age 29 ), however, h e is unfortunately in a second
MVA. H e is brought to the ER, again requiring blood
products.
• H e is type and cross-matched, found to have no
antibodies. H e is pre-treated with
acetaminophen, and transfused 2 units PRBC
without issue.
• The remainder of his hospital course is
unremarkable and the pt is discharged home.
• Ten days after the accident h e follows up at his PCP’s
office with a complaint of fatigue, fevers, and
yellowing of his skin.
• What is the diagnosis?
Delayed Hemolytic Transfusion Reaction
Case 1 (continued)
• Mr gulled is now 78 years old. Since we
last saw h i m , h e has b e e n diagnosed
with diabetes, complicated by ESRD 2/2
diabetic nephropathy for which h e
is dialyzed three times per week.
• H e is admitted for a suspected GI
bleed
for which h e is transfused 2 units
PRBC.
An hour after transfusion, h e starts to
complain of shortness of breath and
chest tightness. HR 120s, BP 180/90,
an
S3 gallop is noted, and new bibasilar
crackles are heard on pulmonary
exam.
Post-transfusion CXR is shown (was https://
previously normal). www.med-ed.virginia.edu/courses/
rad/cxr/pathology2chest.html
• What is the diagnosis?
CXR w/ Sudden SOB.
What is The Most Likely Diagnosis
A) Pulmonary Embolism
B) Transfusion Related Acute Lung Injury
C) Transfusion Associated Circulatory Overload
D) Anaphylaxis
E) Acute Respiratory Distress Syndrome

More common than TRALI (1 in 100 vs 1 in 10,000). This case was


confirmed to b e TACO.
PE usually causes respiratory alkalosis with hypoxia on ABG.
Anaphylaxis should b e considered but TACO is more likely in this scenario.
ARDS is less likely given no evidence of infection or inflammation prior to
the sudden event.
Transfusion-Associated
Circulatory Overload (TACO)
Case 3. Back to Mr gulled…
• Mr gulled is now 80 years old and is admitted after a fall during which
h e sustained a left hip fracture. Following surgery, h e requires 1 unit
PRBC. H e is appropriately type and crossmatched, pretreated with
acetaminophen, and a slow transfusion is initiated during dialysis.
During the transfusion, h e develops diffuse urticaria but is otherwise
stable.
• What is the diagnosis?

umm.ed
Allergic Reactions and Anaphylaxis

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