Adverse Effects of

Blood Transfusion
 Adverse Effects of
Blood Transfusion

 ANY unfavorable consequence is

considered an adverse effect of blood
transfusion. It is also referred to as a
Transfusion Reaction.

 The risks of transfusion must be weighed

against the expected therapeutic benefits.
Complications of blood transfusion

EARLY

 Circulatory overload

 Febrile non-haemolytic reactions

 Allergic reactions

 Haemolytic reactions: immediate or delayed

 Bacterial infections from contamination

 Effects of massive blood transfusions
 Complications (2)

LATE
 Transfusion transmitted infections (TTI)
– Viruses: Hepatitis B, C; HIV I & II; HTLV I & II; CMV
– Bacteria: Treponema pallidum (Syphilis); Salmonella
– Parasites: Malaria; Toxoplasma; Microfilaria

 Immune sensitisation
– Transfusion associated lung injury (TRALI)
– Post-transfusion purpura (PTP)
– Transfusion associated graft-versus-host disease (TA-GvHD)
 Iron overload
 Adverse Effects of Blood Transfusion

1. Acute (<24 hours) Transfusion Reactions - Immunologic

– Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic;
Non Cardiogenic Pulmonary Edema (NCPE)Acute
Transfusion Reactions - Nonimmunologic
– Circulatory overload; Hemolytic (Physical or Chemical destruction of
RBC); Air embolus; Hypocalcemia; Hypothermia
2. Delayed (>24 Hours) Transfusion Reaction - Immunologic
– Hemolytic (Anamnestic response); Graft vs. Host Disease;
Posttransfusion Purpura
– Delayed Transfusion Reactions - Nonimmunologic
– Iron Overload
– Infectious Complications of Blood Transfusion
 Transfusion Reactions

Most common causes of transfusion

related DEATHS:
1. Improper specimen identification
2. Improper patient identification
3. Antibody identification error
4. Crossmatch procedure error
 Most transfusion reactions (not all) are
the result of human error. As you work
through this lecture, consider what could
be done to prevent each outcome.
 Acute Transfusion Reactions
Immunologic

Immediate or Acute Hemolytic Transfusion

Reaction
 Onset within minutes to hours (<24 hours)
 Associated with Intravascular Hemolysis
 Etiology: Antibodies that activate complement to
completion in the vasculature: ABO antibodies
are predominant but not the only ones
implicated.
 Prevention: Give ABO compatible blood.
Intravascular Hemolysis

Signs may include:

Characteristics
 Pain along vein of
 Reaction begins within
infusion site
minutes of infusion
 IgM &/or IgG antibody
 Shock
 RBC Lysis within  Abnormal bleeding
vasculature  Release of cytokines:
 Complement activation to fever, hypotension
completion  Patient apprehension
 Release of histamine and  Renal failure due to Hgb
serotonin
and RBC stroma
Intravascular Hemolysis

Signs & Symptoms continued…

1. Fever or fever & chills
2. Oliguria, may progress to…anuria
3. Sustained hypotension
4. Coagulopathy: May progress to
Disseminated Intravascular Coagulopathy
(DIC)
5. Free hemoglobin in serum & urine
 Acute Transfusion Reactions
Immunologic

Febrile Transfusion Reactions

 Etiology: An INCREASE in temperature of
1OC during infusion of blood component
– Associated with transfusion
– Usually “mild & benign” = not life threatening
– Can have more severe symptoms, not usually
 Non-hemolytic
 Cause: Recipient antibodies to donor
leukocyte antigens
Febrile Transfusion Reactions

Seen in…
 Multiply transfused patients
 Multiple pregnancies
 Previously transplanted
Must rule out…
 Hemolytic transfusion reaction
 Bacterial contamination of unit
Prevention
 Leukocyte reduction or depletion of component.
Acute Transfusion Reactions
Immunologic

Allergic (Urticarial-Hives)
Transfusion Reactions
 Etiology: Form of cutaneous hypersensitivity
triggered by recipient antibodies directed against:
– Donor plasma proteins or
– Other allergens (food, medicines) in donor plasma
 Begins within minutes of infusion
 Characterized by rash and/or hives and itching
 Usually involves release of histamine.
Allergic (Urticarial) Reactions

 MUST be sure that the only reaction is the

development of urticaria
 Must rule out more severe symptoms that
could lead to anaphylaxis:
– angioneurotic edema
– laryngeal edema
– bronchial asthma
 Prevention: Can pre-treat recipient with anti-
histamines before transfusion.
 Acute Transfusion Reactions
Immunologic

Anaphylaxis
 Life threatening!!
 Etiology:
– Recipient is IgA deficient & has anti-IgA in serum
– Recipient anti-IgA can react to even small amounts of
donor IgA in the plasma in any blood component
 Reaction may occur within minutes of beginning
transfusion: Onset of symptoms is SUDDEN
 Prevention: Wash blood components to remove
plasma.
 Anaphylaxis

Symptoms
 Burning sensation at infusion site
 Coughing, difficulty in breathing, and
bronchospasms can lead to cyanosis
 Nausea, vomiting, severe abdominal cramps,
diarrhea
 Hypotension which can lead to shock, loss of
consciousness, & death
 MUST STOP TX’N IMMEDIATELY
 Acute Transfusion Reactions
Immunologic

Non-Cardiogenic Pulmonary Edema

Etiology:
 When transfusion recipient experiences acute respiratory
insufficiency and/or evidence of pulmonary edema without
evidence of cardiac failure.
Mechanism’s
 Primary Suspect: Donor antibodies to recipient WBCs
 Another cause: WBC emboli aggregate in the lungs causing
edema
 Also called TRALI: Transfusion Related Acute Lung Injury
Non-Cardiogenic Pulmonary
Edema (NCPE)

 Symptoms
 Chills, fever, cough, cyanosis, hypotension, increased
difficulty breathing
 Frequently associated with multiple transfusions over a
short period of time
 Prevention: For recipient antibody, give leukoreduced
blood products. For donor antibody, may limit future
donations of that donor.
Acute Transfusion Reactions
NONimmunologic

Circulatory Overload
 Etiology: Rapid increases in blood volume to patient
with compromised cardiac or pulmonary status. (Most
at risk are elderly and pediatric patients) Infusion of
25% albumin is also a cause.
Signs and Symptoms
 Dyspnea, cyanosis, severe headaches, hypertension
or CHF (congestive heart failure).
 Prevention: Stop infusion and place patient in sitting
position. Slow down future infusions.
 Acute Transfusion Reactions
NONimmunologic

Physically or Chemically Induced

Red Cell Destruction
Etiology:
 Destruction of red blood cells in the collection bag
and infusion of free hemoglobin, etc.
Improper temperatures: High or Low
 Microwave blood bag, malfunctioning blood warmer or
water bath, inadvertent freezing of blood.
 Physically or Chemically Induced
Red Cell Destruction

Osmotic Hemolysis
 Addition of drugs or hypotonic solutions (5%
dextrose, deionized water, etc.) to transfusion.
Mechanical Hemolysis
 Caused by rollers in blood pump
 Pressure infusion pumps
 Small bore needles
 Prevention: Adherence to procedures for all
aspects of procuring, processing, issuing and
administering red blood cell transfusions.
Acute Transfusion Reactions
NONimmunologic

Hypocalcemia
 Excess citrate: When plasma (or platelets) are infused
at rate >100 mL/minute or individuals with impaired liver
function:
– Citrate is broken down by liver.
 Seen more in pediatric and elderly patients
 Signs and Symptoms: Facial tingling, nausea, vomiting.
 Prevention: Slowing or discontinuing infusion.
Administration of Calcium is not usually necessary.
Acute Transfusion Reactions
NONimmunologic

Hypothermia
 Etiology: Drop in core body temperature due to
rapid infusion of large volumes of cold blood.
Especially if using central cardiac catheter.
 Symptoms: Decreased body temperature and
ventricular arrhythmias.
 Seen in small infants or massive transfusion
 Prevention: Reduce rate of infusion or use
blood warmers. Pull catheter away from heart.
Acute Transfusion Reactions
NONimmunologic

Air Embolism
 Etiology: If blood in an open system is infused
under pressure or if air enters the system while
container or blood administration sets are being
changed. Infusion of air.

 Treatment: Place patient on left side with head

down to displace air bubble from pulmonic valve.
Delayed Transfusion Reactions
Immunologic

Delayed Hemolytic Transfusion

Reaction
 Onset within days (Anamnestic response,
>24 hours)
 Associated with Extravascular Hemolysis
 Etiology: Antibodies that usually do NOT
activate Complement to completion: Rh,
Kell, etc.
 Prevention: Give antigen negative blood.
 Extravascular Hemolysis

Characteristics
Signs may include:
 Reaction within hours to  No release of free Hgb,
days
RBC stroma, or enzymes
 Antibody attaches to RBC: into circulation
RBC destroyed in spleen or
liver, etc.
 May be immediate (hours)
or delayed (days)
 Commonly IgG
 May have bilirubinemia or
 May or may not activate
Complement
bilirubinuria
Extravascular Hemolysis

Signs & Symptoms continued…

1. Fever or fever & chills
2. Jaundice
3. Unexpected anemia
• Some may present as an ABSENCE of an
anticipated increase in Hemoglobin and
hematocrit.
 Delayed Transfusion Reaction
Immunolgic

Graft vs Host Disease (GVHD)

 Etiology Donor T-Lymphocytes attack recipient
(host) tissues.
 Groups at risk:
– Immunocompromised patients(Cancer, fetus, neonatal,
bone marrow transplant and HIV).
 Signs: Fever, dermatitis, or erythroderma,
hepatitis, diarrhea, pancytopenia, etc.
 Prevention: Irradiation of blood products.
 Delayed Transfusion Reaction Immunolgic

Post-transfusion Purpura
 Etiology: Antibodies to platelet antigens causes
abrupt onset of severe thrombocytopenia (platelet
count <10,000/l) 5-10 days following transfusion.
 Signs: Purpura, bleeding, fall in platelet count
 Prevention: High dose intravenous
immunoglobulin (IVIG)
 Delayed Transfusion Reaction
NONimmunolgic

Iron Overload
 Etiology: Excess iron resulting from chronically
transfused patients such as hemoglobinopathies, chronic
renal failure, etc.
 Signs: Muscle weakness, fatigue, weight loss, mild
jaundice, anemia, etc.
 Treatment: Removal of iron without reducing patients
circulating hemoglobin. Infusion of deferoxamine - an iron
chelating agent has been useful.
 Infectious Complication of Blood
Transfusion

Bacterial Contamination
 Etiology: At what point is the bacteria introduced
into the donor unit?
– At time of collection: either from the donor or the
venipuncture site.
– During component preparation, etc.
 Usually involves endotoxins
– Pseudomonas, Escherichia coli, Yersinia
enterocolitica
Bacterial Contamination

 Components: Most often from platelet

components (room temp). Red cell units will look
dark.
 Symptoms: Rapid onset
– Fever, hypotension, shaking chills, muscle pain
– Vomiting, abdominal cramps, bloody diarrhea,
hemoglobinuria, shock, renal failure, & DIC.
 Bacterial Contamination

Transfusion must be stopped immediately

 Gram stain & blood cultures should be done
on the unit, patient and all infusion sets
associated with the patient at the time of
transfusion.
 Broad-spectrum antibiotics should be given
immediately intravenously
 Prevention: Maintain standards of donor
selection, blood collection and proper
maintenance of collected blood components.
Massive blood loss

 Medical emergency
– Loss of one blood volume within 24 hour period
– 50% blood volume loss within 3 hours
– Rate of blood loss  150ml/min
 Any blood loss >2L (SGH)
 Usually occurs in A&E, operating theatre or
obstetric department
 High morbidity & mortality
 Massive Blood Loss (2)

 Ensure adequate venous access

 Attempt to maintain blood volume with saline,
plasma expanders
 ‘Flying squad’ blood (O Rh Neg, CMV neg)
available if blood required in 15 minutes
Massive Blood Loss:
A Vicious Cycle

Haemorrhage

Dilution of clotting
factors/DIC
and
thrombocytopenia

Massive Blood
Transfusion
Massive Blood Loss (3)

 Call Blood Bank for :

“Code Red”
“Code Blue” – Obstetrics

 Blood products issued automatically

 First Stage
– 6 units blood
– 1 litre FFP
– 2 pools platelets
 Massive Transfusion: complications

 Hypothermia  acidosis
 Hyperkalaemia: K+ leaks out of red cells during
storage
 Citrate toxicity additive solution (SAG-M)
 Hypocalcaemia: Ca2+ ions bound by citrate
 Depletion of platelets and coagulation factors :
red blood cells kept in citrate plus
 Fluid overload  acute respiratory distress
syndrome (ARDS)
Transfusion Reaction
Follow-up

Clinical Information Needed:

 Recipient diagnosis
 Medical history of pregnancy &/or
transfusion
 Current medications
 Signs & symptoms during transfusion
reaction
 How many mL’s of RBC’s or plasma were
transfused?
Clinical Information Needed

 Were rbc’s cold or warm when transfused?

– Was a blood warmer used?
– Was component manipulated in any way? Water bath,
refrigerator, freezer, etc.
 Were red cells infused under pressure?
 What was the size of the needle used?
 Were other solutions given through the IV line at the
same time? If so what?
 Were any other drugs given at the time of
transfusion? If so, what?
 What were pre- & post- transfusion vital signs?
 Transfusion Reaction Follow-up
Post Transfusion Reaction blood samples to be collected
from the recipient:

 Clotted specimen  Repeat ABO, Rh, IAT and

Crossmatch. Visual check for
 EDTA specimen hemolysis and compare with pre
transfusion sample.
 Clotted specimen
 DAT (Direct Antiglobulin Test)
 1st voided urine
 Collect 5-7 hours post
specimen post-tx’n transfusion to check for
bilirubin
 Free hemoglobin determination
 Transfusion Reaction Workup

CLERICAL CHECKS SPECIMEN CHECKS

1. Correct identification of  Visual inspection of post-
patient, specimen, and transfusion specimen
transfused unit.  Check of records for
hemolysis in pre-transfusion
2. Agreement of records and specimen:
history with current results – detectable at 20mg/dL
and interpretation of  Post transfusion bilirubin
results. monitoring
3. Correct labeling of  Visual inspection of Blood
transfused unit bag and lines
Post Transfusion Lab Testing

Direct Antiglobulin Test (DAT)

 Recipient post-tx’n spec. (DO THIS FIRST)
 Positive? Perform eluate and identify antibody

ABO Grouping and Rh Typing

 Recipient pretransfusion and posttransfusion specimen
 Donor segment and bag.
Post Transfusion Lab Testing

Crossmatch
 Recipient pre-transfusion sample with unit and pre-
transfusion sample with segment
 Recipient post-transfusion sample with unit and post-
transfusion sample with segment
Indirect Antiglobulin Test (IAT)
 Recipient Pre- & post-transfusion reaction
specimens
 Positive? Identify antibody and compare results of
serum panel with eluate panel.
THANK YOU