Adverse Effects

of
Blood
Transfusion
Dr. Dileetha Kuruppu
Consultant Transfusion Physician
TH Peradeniya
 Transfusion of Blood

Therapeutic Benefits Risks in blood Tx

of blood Tx
‫ ٭‬Improve O2 carrying capacity ‫ ٭‬Immunological risk
‫ ٭‬Ensure haemostasis ‫ ٭‬Infection risk
‫ ٭‬Enhance resistance against ‫ ٭‬Procedural risk
infection

Prescribe only when the benefits clearly overweigh risks

 Definition
• Any adverse outcome attributable to
transfusion of a blood component or
components.

• 10% of Tx recipients may suffer from adverse effects.

• Majority of Tx reactions are uneventful and
unnoticed.
Acute – during or within 24 hours of Tx
Delayed – after 24 hours
Immunological Transfusion
Reactions
 Immune Transfusion Reactions

• Classical “Transfusion Immune Reaction” →

interactions between the RECIPIENTS inherited or acquired
antibodies with their relevant antigens that are present in
the cellular or humoral components of the DONOR’s blood
products
➢ Due to Ab’s against donor Antigens
-RBC
-WBC
-Platelets
➢ Reaction due to plasma proteins
➢ Passively Transfused Abs in Donor plasma
Acute Haemolytic Transfusion Reaction

Causes for acute haemolysis

1. Red cell incompatibility - ABO incompatibility
2. Accidental freezing or heating of RBC
3. Red cells contact with water or 5% Dextrose
4. Bacterial contamination of red cells
5. Administration of RBC through narrow gauge needle
ABO Incompatibility –
• Most dangerous immunological complication
• Tx of incompatible donor RBC into a patient
• Antibodies fix compliments and cause
Intravascular Haemolysis

Causes
1. Clerical errors – Commonest cause (68%)

2. Technical errors (29%)

 Clinical Features
Symptoms Signs
Chills Fever
Chest / back/loin pain Rigors
Headache Flushing
Restlessness
Palpitation Hypotension
Dyspnoea Tachycardia
Nausea
Vomiting Haemoglobinurea
Pain at the infusion site Bleeding
• Investigation of AHTR
• Haematological Ix
- FBC/BP
- coagulation screening
• Biochemical Ix
-Collect first urine sample for haemoglobinurea
- urea & creatinine/ SE
- Haptoglobin, LDH
Management of AHTR
• Stop Tx immediately
• Maintain IV line with N Saline
• Check the blood pack and the patient identity(clerical check)
• Report the reaction immediately to the BB
• Monitor closely (PR, BP, RR, UOP)
• Provide cardio respiratory support
• Rx the reaction
Hypotension- N Saline 20-30 ml/kg
-Inotropics like Dopamine
Ensure diuresis maintain UOP 1ml/kg/h
- Frusemide 40-80 mg iv
- Expert Renal Advise if ARF → Dialysis
DIC – supportive therapy with blood components
Investigation at the Blood Bank

Record the type of reaction, length of Tx, volume, type of the

component, and unit number
• Collect 5cc clotted and 2cc EDTA blood samples send
remaining blood pack and tubing with reaction form to the
blood bank

• BB Ix
- Pre Tx sample→ ABO/Rh/XM
- Post Tx sample→ ABO/Rh/DAT/XM/Hb’aemia
- Donor pack→ ABO/Rh
Prevention

Maintain vain to vain quality

– Identification of pt before sampling
– Label sample at the bed side
– Good laboratory practice
– Correct identification of pt before Tx
– Careful monitoring of pt for first 20 min of each
unit of Tx
– Proper storage and handling of blood
 Febrile Non- Haemolytic
Transfusion Reactions
A. Chills followed by fever +/- Rigors
1. Most common symptom
2. Temperature increase of > 1°C from
baseline
3. Usually occurs during or within a few hours
of transfusion completion
B. Tachycardia
C. Mild dyspnoea
D. Headache, Flushing
• Temperature usually settles after stopping the
transfusion
• The reactions may cause significant discomfort
to patients, be frightening to patients and
caregivers, Refuse Tx
Severity of clinical symptoms depends on
i. No: of leucocytes/ Quantity of Cytokines
ii. Speed of Tx
iii. Titer of Anti-leucocyte antibodies
Pathogenesis
➢ Red Cell Transfusions

• Previous Tx &/or Pregnancies

• Antibodies to HLA , HNA antigens reacting with

donor leucocytes

Recipient Abs bind to Donor leucocyte Ags

↓
Activate recipients Leucocytes
↓
secrete Pyrogens (IL-1,TNF)
➢ Platelet Transfusion
• Without prior sensitization

• Due to presence of Pyrogenic Cytokines

IL-1β, IL-6 & TNF-α released from leucocytes
during the 5 day platelets storage

Theory supported by
a. Very high levels of Cytokines during storage
b. Not prevented by bedside filtration
c. No ↑ of Cytokines if pre-storage leucocyte
filtered
➢Management
• Acute Mx
– Stop transfusion, assure that it’s not an acute
hemolytic reaction – Signs/Symptoms
– Clerical Check – right patient, right unit,
- Give Paracetamol

If temperature < 1.50C /BB Ix negative & HTR

excluded can recommence the Tx
Start Tx slowly with regular monitoring
If the temperature > 1.50C do not start the Tx.
Send the pack, giving set & post Tx sample to BB.
➢Reaction to Platelet Tx
• Slow the Tx
• Keep the patient warm
• Give antipyretic
• Complete the transfusion if no progression of
the symptoms
➢ Prevention
• If recurrent febrile episodes or Pt on long-term Tx
support
• BCR→ 5 x108 WBC per unit will prevent FNHTR
• LD→ 5 x 106 WBC per unit will also prevent HLA
sensitization

a) Removal of Leucocytes from RCC/Plt

1. Differential sedimentation
2. Use of Leuco-depletion Filters
Pre-storage filtration of RCC & Platelet
3. Washing of RCC
Remove 90% of leucocytes
4. Freezing & Thawing of RCC
98% of leucocytes & 100% of plt & plasma
removed.
 Allergic & Anaphylactic Reactions
Signs & Symptoms
Urticaria, pruritis, Wheezing, Severe dyspnoea,
Angioedema, Hypotension, Anxiety, Shock, Cardiac
arrest

➢ Mainly due to patient’s Ab’s reacting with Plasma

proteins in the transfused product
➢ Common in patients with repeated plasma
component therapy
➢ IgA deficient more likely at risk (1:300 – 1:500)
Anaphylaxis
IgE bound to mast cells are present when previously
sensitized.

Mast cells contain histamine and circulate with bound

IgE.

Histamine
IgE
2-

A B C
Antigens from plasma Antigen binding causes Histamine is released
bind to pre-formed IgE activation of histamine from mast cells and
attached to mast cells release mechanism from causes increase in
mast cells. vascular permeability
Management
• Stop Tx immediately
• Rx Shock ( IV Crystalloids/Adrenaline/Anti-
Histamine/O2)
• Monitoring/ ICU

Prevention
• Washed/ Autologous/from IgA Deficient Donors
 Transfusion-related acute lung
injury: TRALI
• Acute dyspnoea with hypoxia and bilateral
pulmonary infiltrates during or within six hours of
transfusion, not due to circulatory overload or
other likely cause.
• Due to reaction between donor leucocyte
antibodies with recipient granulocytes
• Vascular damage & change in permeability of
pulmonary vasculature causes oedema
• TRALI is common after Tx of plasma rich
components such as WB, PC, FFP, Cryo
Clinical Features

– Fever with chills

– Chest pain
– Nonproductive cough
– Severe hypoxia
– cyanosis
– Severe bilateral pulmonary oedema
– Acute respiratory distress
– Hypotension
Pathophysiology
2 HIT Theory
• Leukocyte Antibodies
– Antibody to donor
leukocyte
– Ab to HLA I, II,
granulocyte, monocyte,
IgA
– Neutrophil in pulmonary
capillary → pulmonar
damage & capillary leak
– Transient leukopenia
• Biologically Active
Substance
– Patients condition
• Sepsis, Sx, Ck Rx,
Massive Tn
– Active substance
• Lipid & cytokines
• Abs C = complement; HLA = human leukocyte antigen; IL = interleukin; LPS = lysophosphatidil
choline; PAF = platelet activating factor; TNF = tumor necrosis factor; 5b, NA, NB = neutrophil
antigens
 D/D: think more before TRALI
1. Underlying pulmonary disease
2. Underlying cardiac disease such as CHF
3. Transfusion- associated circulatory overload (TACO)
4. Severe allergic or anaphylactic reactions
5. All risk factors for acute lung injury
• Direct Lung Injury
– Aspiration
– Pneumonia
– Toxic inhalation
– Lung contusion
– Near drowning
• Indirect Lung Injury
– Severe sepsis
– Shock
– Multiple trauma
– Burn injury
 LAB Diagnosis
Confirm diagnosis
• Chest X ray – peri-hilar, nodular shadowing in the mid
and lower zone
• Donor HLA & HNA Ab status
• Finding of specific Ag in patient
• Lymphocytotoxic Crossmatch
• Normal CVP, PW Pressure
• Normal ECHO
• Oxygen saturation is < 90% on room air
Treatment
– Prompt, Vigorous Respiratory Support
– Intubation, Mechanical Ventilation
– Critical Care Support
Prevention
– No further plasma-containing blood products from
the implicated donor
– Producing FFP, Apheresis platelets only from male
donors
– Screening previously pregnant and previously
transfused donors for HLA antibodies →plasma
rich components donors
– Improving tests for the detection of white blood
cell antibodies
– Removal of plasma from cellular blood products
→ Additives
 Delayed Hemolytic Transfusion Reaction
(DHTR)
DHTR defined as fever and other symptoms / signs of
haemolysis more than 24 hours after transfusion;
confirmed by one or more of: a fall in Hb or failure of
increment, rise in bilirubin, positive DAT and positive
cross-match not detectable pre-transfusion.
• Mechanism
– Antibodies that exist in low titers prior to the transfusion
– Typically to the Kidd, Duffy or Kell system
– 2ry Immune Response
– Resulting Extra vascular red cell destruction
– Usually occur 5-10 days after Tx
• Signs and Symptoms:
– Worsening of anaemia (fall in Hb)
– Fatigue/ Malaise, Fever, mild jaundice (Common)
– Haemoglobinemia,
– Renal failure (Rare)
• Investigations:
– BP→ Spherocytosis
– FBC, S. Bilirubin, LFT, RFT
– DAT + Usually IgG→ Elute; offending Antibody Sp.
– LDH & Haptoglobin
– Pre/ Post TX Samples (Pack?)- Serology
Management
• As long as clinically mild, no treatment necessary
• If Anemia →Tx antigen negative RCC
• Renal failure, Hypotension →Expert Advice

• PREVENT it from happening the next time –

REPORT TO THE BLOOD BANK, Antibody Card,
Good record maintenance
– Do IAT Ab screening prior to Tx especially for Tx dependent
Frequently transfused pt’s
– Do IAT Cx for all transfusions as much as possible
– Provide Ag negative blood for pt’s with clinically significant
Ab’s
ALMOST IMPOSSIBLE TO PREVENT……………………?
Non- Immunological Transfusion
Reactions
 Bacterial Contamination
Platelets Red Cells
• Staphylococcus epidermis/ •Yersinia enterocolitica
aureus •Pseudomonas fluorescens
• Serratia marcescens •Serratia liquefaciens
• Salmonella cholerae
• Bacillus cereus
• Streptococcus
Sources of Bacterial Contamination
◼Skin Surface Contamination
◼Donor Bacteraemia
◼Containers and Disposables
◼Environment
 Signs and Symptoms of Transfusion-Associated
Bacterial Sepsis

• Fever >20c • Nausea and vomiting

• Rigors (shaking chills)
• Tachycardia
• Change in systolic blood
pressure, Collapse &
Shock.
• Shortness of breath
• Lumber (lower back)
pain
• Hb’uria, Bleeding
manifestations
• Features of Renal
Failure
Investigation
• Inform the blood bank immediately
• Blood grouping- Pre, Post and Pack
• Examine the blood pack for haemolysis, discoloration,
air, clots and pin hole defects
• Gram stain of pack and tube contents, Blood culture
• Blood culture of the recipient
• FBC, BU/SE, S. Creatinine, Coagulation screening
Management
• Stop Tx immediately
• Start IV N. Saline
• Broad spectrum antibiotics
• Inotropes for hypotension
• Blood components for DIC

Prevention
1. Bacterial avoidance
2. Growth inhibition
3. Bacterial detection
4. Bacterial elimination
Transfusion Associated Circulatory
Overload (TACO)
• Rapid onset after a significant volume of fluid infused
• Infusion too rapid, volume infused too great or to
patients with impaired renal function.
• Results heart failure and pulmonary oedema

Clinical Features

• Rapid ↑ in BP, Rapid thready pulse

• ↑RR, dyspnoea, cough, pink frothy sputum
• ↑JVP & CVP
• Nausea, Vomiting
Management
• Stop Tx
• Prop up , administer O2, Diuretic (Frusemide 1-2mg/kg iv)
• Cardio- pulmonary support

Prevention
• Tx of required component only
• Monitor fluid balance (esp. in elderly, children and pt’s
with CVS or renal disease)
• Tx slowly with diuretics
• Avoid routine Tx at night
 Iron Overload
• One unit RCC will give 250 mg iron
• No physiological mechanism to eliminate excess iron
• In Tx dependent pt’s over long period of time
accumulate iron in the body resulting Haemosiderosis
• Excess iron deposition causes organ failure – heart,
liver, endocrine

Management and Prevention:

• Iron chelation therapy is usually commenced early in
the course of chronic Tx therapy
• Iron binding agents such as Desferrioxamine
Thank You………