Blood Groups and Transfusion Reactions

Blood Group Systems

ABO System

• The ABO system is the most clinically significant blood group system, discovered by Karl Landsteiner in 1900.
• It is based on the presence or absence of A and B antigens on red blood cell membranes and corresponding naturally occurring antibodies in plasma.

Antigen Structure:

• A and B antigens are glycoproteins consisting of a basic precursor (H antigen) modified by specific glycosyltransferases
• Type A individuals have N-acetylgalactosamine added to H antigen
• Type B individuals have galactose added to H antigen
• Type O individuals have H antigen only (no further modification)
• Type AB individuals express both modifications

Antibody Formation:

• Anti-A and anti-B are naturally occurring IgM antibodies
• Develop in first 6 months of life through exposure to environmental antigens
• Do not require prior sensitization
• Capable of complement activation and intravascular haemolysis
• Present in plasma when corresponding antigen absent from red cells

Blood Group Distribution:

• Type O: ~45% (universal donor for red cells)
• Type A: ~40%
• Type B: ~11%
• Type AB: ~4% (universal recipient)

Inheritance:

• Codominant alleles A and B; recessive allele O
• Both A and B are dominant over O
• ABO genes located on chromosome 9

Rhesus System

The Rh system comprises over 50 antigens, with the D antigen being most immunogenic and clinically important.

D Antigen Characteristics:

• Protein antigen embedded in red cell membrane
• Present in 85% of Caucasian population (Rh positive)
• Highly immunogenic; approximately 80% of Rh-negative individuals develop anti-D after single exposure to Rh-positive blood
• No naturally occurring anti-D antibodies
• Antibodies develop only after exposure (transfusion or pregnancy)

Anti-D Antibodies:

• Predominantly IgG class
• Cross placenta
• Cause delayed haemolytic transfusion reactions
• Responsible for haemolytic disease of the newborn
• Cannot activate complement efficiently
• Cause extravascular haemolysis via splenic macrophages

Other Rh Antigens:

• C, c, E, e are less immunogenic but clinically significant
• May cause transfusion reactions in sensitized individuals
• Important in multiply transfused patients

Other Blood Group Systems

Kell System:

• K antigen highly immunogenic (third most important after ABO and D)
• Anti-Kell antibodies cause severe haemolytic disease of newborn
• IgG antibodies develop after transfusion or pregnancy

Duffy System:

• Clinically significant in multiply transfused patients
• Duffy-negative phenotype provides resistance to Plasmodium vivax malaria

Kidd System:

• Antibodies may cause delayed haemolytic transfusion reactions
• Antibody levels may fall below detection, then rapidly increase upon re-exposure

MNS System:

• Usually clinically insignificant
• Rarely cause transfusion reactions

Transfusion Reactions Classification

Acute Haemolytic Transfusion Reactions

Pathophysiology:

• Most commonly due to ABO incompatibility (clerical error)
• IgM antibodies bind to incompatible red cells
• Complement activation cascade initiated
• Formation of membrane attack complex (C5b-C9)
• Intravascular haemolysis with release of free haemoglobin
• Activation of coagulation cascade and inflammatory mediators

Clinical Features:

• Onset within minutes to hours
• Fever, chills, rigors (cytokine release)
• Hypotension (anaphylatoxins C3a and C5a)
• Tachycardia, dyspnoea
• Chest and back pain
• Haemoglobinuria (red/brown urine)
• Signs may be masked under general anaesthesia
• Unexplained bleeding, oozing from surgical sites (DIC)

Complications:

• Disseminated intravascular coagulation
• Acute kidney injury (haemoglobin precipitation in tubules, hypotension)
• Acute respiratory distress syndrome
• Mortality rate 10-50% if not recognized and treated promptly

Laboratory Findings:

• Positive direct antiglobulin test (DAT/Coombs)
• Elevated unconjugated bilirubin
• Decreased haptoglobin
• Elevated lactate dehydrogenase
• Free plasma haemoglobin
• Coagulation abnormalities (prolonged PT, APTT, low fibrinogen, elevated D-dimer)

Delayed Haemolytic Transfusion Reactions

Mechanism:

• Occurs 3-14 days post-transfusion
• Due to anamnestic response to minor blood group antigens
• Previous sensitization not detected in pre-transfusion testing
• Antibody levels were below detection threshold
• Re-exposure triggers rapid IgG antibody production
• Predominantly extravascular haemolysis by reticuloendothelial system

Clinical Features:

• Generally less severe than acute reactions
• Fever, jaundice
• Falling haemoglobin concentration
• May be asymptomatic with laboratory findings only
• Rarely causes renal failure

Common Antibodies:

• Kidd (Jka, Jkb)
• Rh (E, c, C)
• Duffy (Fya)
• Kell (K)

Febrile Non-Haemolytic Transfusion Reactions

Mechanism:

• Most common transfusion reaction (1-3% of transfusions)
• Cytokine-mediated response
• Cytokines accumulate during blood storage
• Recipient antibodies against donor leukocytes
• Release of inflammatory mediators

Clinical Features:

• Temperature rise ≥1°C during or within 4 hours of transfusion
• Chills, rigors
• No evidence of haemolysis
• Self-limiting

Prevention:

• Leukoreduction of blood products
• Pre-medication with paracetamol (limited efficacy)

Allergic Transfusion Reactions

Mechanism:

• Type I hypersensitivity reaction
• Recipient antibodies against donor plasma proteins
• Mast cell and basophil degranulation
• Histamine and mediator release

Clinical Features:

Mild (Most Common):

• Urticaria, pruritus
• No systemic symptoms
• Occurs in 1-3% of transfusions

Severe (Anaphylaxis):

• Bronchospasm, laryngeal oedema
• Hypotension, cardiovascular collapse
• May occur with IgA deficiency (anti-IgA antibodies)
• Incidence approximately 1:20,000-50,000 transfusions

Management:

• Mild: antihistamines, continue transfusion if symptoms resolve
• Severe: stop transfusion, adrenaline, resuscitation

Transfusion-Related Acute Lung Injury (TRALI)

Pathophysiology:

• Non-cardiogenic pulmonary oedema
• Two-hit hypothesis:
  • First hit: underlying patient condition (sepsis, surgery, inflammation)
  • Second hit: donor antibodies or bioactive lipids
• Most commonly due to donor anti-HLA or anti-neutrophil antibodies
• Neutrophil activation and sequestration in pulmonary capillaries
• Increased capillary permeability

Clinical Features:

• Acute respiratory distress within 6 hours of transfusion
• Hypoxaemia (PaO₂/FiO₂ <300 mmHg)
• Bilateral pulmonary infiltrates on chest radiograph
• No evidence of cardiac failure or fluid overload
• Fever, hypotension, tachycardia may occur

Incidence and Mortality:

• Occurs in 1:5,000-10,000 transfusions
• Third leading cause of transfusion-related death
• Mortality 5-10%

Management:

• Supportive respiratory care
• Mechanical ventilation if required
• Usually resolves within 48-96 hours

Prevention:

• Use of male donor plasma preferentially
• Testing female donors for HLA antibodies

Transfusion-Associated Circulatory Overload (TACO)

Mechanism:

• Cardiogenic pulmonary oedema
• Volume overload from rapid or excessive transfusion
• Particularly in patients with cardiac dysfunction or renal failure

Clinical Features:

• Dyspnoea during or within 6 hours of transfusion
• Elevated jugular venous pressure
• Pulmonary oedema on chest radiograph
• Elevated B-type natriuretic peptide
• Hypertension (distinguishes from TRALI)

Risk Factors:

• Pre-existing cardiac disease
• Renal impairment
• Elderly patients
• Positive fluid balance
• Rapid transfusion rate

Management:

• Diuretics
• Oxygen therapy
• Slow transfusion rate
• May require non-invasive ventilation

Transfusion-Associated Graft-versus-Host Disease

Mechanism:

• Viable donor T lymphocytes engraft and proliferate
• Attack recipient tissues
• Occurs in immunocompromised recipients
• Donor cells not recognized as foreign

Clinical Features:

• Onset 1-4 weeks post-transfusion
• Fever, rash, diarrhoea
• Liver dysfunction
• Bone marrow aplasia
• Mortality >90%

Prevention:

• Irradiation of blood products for at-risk patients
• Dose: 25 Gy to blood component
• Indications: immunocompromised patients, directed donations from relatives, HLA-matched platelets

Bacterial Contamination

Sources:

• Skin flora during venepuncture
• Asymptomatic bacteraemia in donor
• More common in platelets (stored at room temperature)

Clinical Features:

• High fever (>2°C rise)
• Rigors, severe hypotension
• May progress to septic shock
• Can be rapidly fatal

Common Organisms:

• Red cells: Yersinia enterocolitica (grows at 4°C)
• Platelets: Staphylococcus species, Bacillus species

Pre-Transfusion Testing

Type and Screen

Blood Typing:

• Determination of ABO and Rh(D) status
• Forward typing: patient cells tested with anti-A and anti-B reagents
• Reverse typing: patient serum tested with known A and B cells
• Both must agree for valid result

Antibody Screen:

• Patient serum tested against panel of reagent red cells
• Detects clinically significant unexpected antibodies
• If negative, allows issue of blood without crossmatch in some systems

Crossmatch

Purpose:

• Final compatibility check before transfusion
• Detects ABO incompatibility and unexpected antibodies

Types:

Immediate Spin (IS):

• Room temperature phase
• Detects ABO incompatibility
• Rapid (5 minutes)

Antiglobulin Crossmatch:

• Full compatibility testing
• Includes 37°C incubation and antiglobulin phase
• Takes 45-60 minutes
• Detects IgG antibodies

Electronic/Computer Crossmatch:

• If antibody screen negative
• Patient ABO/Rh verified
• Computer verifies ABO compatibility
• Allows rapid issue of blood

Emergency Transfusion

Group O Red Cells:

• Universal donor for red cells
• O negative for females of childbearing age
• O positive acceptable for males and post-menopausal females
• Contains no A or B antigens

Group AB Plasma:

• Universal donor for plasma
• Contains no anti-A or anti-B antibodies

Uncrossmatched Blood:

• Risk of incompatibility approximately 1:1,000
• Use when life-threatening haemorrhage and cannot wait for crossmatch
• Switch to type-specific blood as soon as available

Clinical Relevance

Anaesthetic Implications

Pre-operative Assessment:

• Review transfusion history and previous reactions
• Patients with antibodies may require extended crossmatch time
• Rare blood types may necessitate ordering blood well in advance
• Document blood group for emergency reference

Intraoperative Management:

• Most transfusion reactions manifest differently under general anaesthesia
• Unexplained hypotension, tachycardia, or bleeding may be only signs
• High index of suspicion required
• Monitor urine output and colour
• Regular observation of surgical field for abnormal bleeding

Massive Transfusion:

• Risk of TACO increases with rapid administration
• Hyperkalaemia from stored blood (potassium leaks from red cells during storage)
• Hypocalcaemia from citrate in stored blood (binds calcium)
• Hypothermia from cold blood products
• Coagulopathy from dilution and consumption

Transfusion Reaction Management:

• Stop transfusion immediately if reaction suspected
• Maintain IV access with new line
• Support airway, breathing, circulation
• Notify blood bank immediately
• Return blood unit and obtain fresh samples for repeat crossmatch
• Collect urine sample to check for haemoglobinuria
• Send blood for FBC, coagulation, biochemistry, blood cultures
• Document all clinical observations

Prevention Strategies:

• Strict adherence to patient identification protocols
• Two-person verification at bedside
• Leukoreduction reduces FNHTR and HLA alloimmunization
• Irradiation prevents TA-GVHD in immunocompromised
• Appropriate transfusion triggers (restrictive strategy for most patients)
• Use blood warmers for rapid or large volume transfusions

Special Populations:

• Patients with multiple antibodies require specialized blood products
• May need rare donor panels or autologous transfusion
• Jehovah's Witnesses: cell salvage, acute normovolaemic haemodilution
• Consideration of alternatives: tranexamic acid, iron therapy, erythropoietin