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
Sources