Transfusion Medicine

Blood Products

Component therapy: principles and classifications

Modern transfusion practice uses component therapy rather than whole blood, allowing targeted replacement of oxygen-carrying capacity, haemostasis, or plasma proteins while limiting volume and donor exposure. In the UK, cellular components are universally leucodepleted to reduce febrile reactions, HLA alloimmunisation and CMV transmission risk; residual leucocyte count is typically <1 × 10⁶ per unit. Products may be modified further: irradiated components prevent transfusion-associated graft-versus-host disease by inactivating donor lymphocytes; washed components reduce plasma proteins, useful in recurrent severe allergic reactions or IgA deficiency; CMV-seronegative components are reserved for selected high-risk groups, though leucodepletion substantially reduces CMV risk.

Product	Typical adult dose	Expected effect	Storage/shelf-life	Key indications
Red cell concentrate	1 unit, reassess; approximately 250–300 mL	Hb rise ~10 g/L per unit in a 70 kg adult	2–6°C; up to 35 days depending on additive solution	Symptomatic anaemia, acute blood loss, peri-operative optimisation
Platelets	1 adult therapeutic dose: pooled or apheresis, usually ≥2.4 × 1011 platelets	Increment 20–40 × 109/L at 1 hour if not consumed	20–24°C with agitation; usually 5–7 days	Bleeding or prophylaxis in severe thrombocytopenia; platelet dysfunction
Fresh frozen plasma	12–15 mL/kg, often 4 units in adult	Replaces multiple coagulation factors; larger volumes needed for meaningful INR correction	Frozen ≤−25°C; after thawing usually 24 h at 2–6°C	Bleeding with multiple factor deficiency, massive haemorrhage, DIC with bleeding
Cryoprecipitate	2 adult pools, commonly equivalent to 10 donor units	Raises fibrinogen by ~1 g/L in adult	Frozen; use soon after thawing	Hypofibrinogenaemia, dysfibrinogenaemia with bleeding

Red cell transfusion

Red cells provide haemoglobin-mediated oxygen delivery; the decision to transfuse should integrate haemoglobin, active bleeding, cardiopulmonary reserve, symptoms and trajectory rather than a single value. Restrictive transfusion strategies are standard in stable adults. The landmark TRICC trial demonstrated that a restrictive threshold of Hb <70 g/L was at least as safe as a liberal threshold of 100 g/L in critically ill patients, with possible mortality benefit in less severely ill patients. NICE and AABB guidance generally support transfusion at Hb <70 g/L with a post-transfusion target 70–90 g/L in stable non-bleeding adults; in acute coronary syndrome, many guidelines use a higher threshold, commonly 80 g/L, reflecting limited and mixed trial data.

One unit should be prescribed at a time in stable non-bleeding patients, followed by clinical and laboratory reassessment. Red cells contain minimal viable platelets or coagulation factors; massive red cell-only transfusion therefore causes dilutional coagulopathy unless balanced component replacement is used.

Platelet components

Platelets may be pooled from buffy coats or collected by apheresis; apheresis reduces donor exposure and facilitates HLA/HPA-matched support in refractory patients. Platelet increments are impaired by sepsis, splenomegaly, DIC, fever, bleeding, drugs and immune alloimmunisation. The corrected count increment measured 10–60 minutes and at 18–24 hours helps distinguish immune from non-immune refractoriness.

• Prophylaxis: stable haematology patients commonly receive platelets at <10 × 10⁹/L; use <20 × 10⁹/L with sepsis, fever, mucositis or rapid fall.
• Procedures: many invasive procedures require >50 × 10⁹/L; central venous catheter insertion may be safe at lower thresholds in experienced hands; neurosurgery or posterior eye surgery usually requires >100 × 10⁹/L.
• Bleeding: therapeutic transfusion is guided by severity, platelet count and platelet function, including antiplatelet drugs and uraemia.

Plasma, cryoprecipitate and factor concentrates

Fresh frozen plasma contains all soluble coagulation factors but has relatively low factor concentration, making it inefficient for mild INR prolongation. It should not be used merely to “correct” an abnormal INR in a non-bleeding patient before low-risk procedures. Clinically meaningful correction is unlikely when the INR is only mildly prolonged, for example <1.5. In major haemorrhage, plasma is given early as part of protocolised resuscitation, commonly approximating a 1:1 to 1:2 plasma:red cell ratio until coagulation tests or viscoelastic assays guide therapy.

Cryoprecipitate is enriched in fibrinogen, factor VIII, factor XIII, von Willebrand factor and fibronectin. In major bleeding, fibrinogen is often the first coagulation factor to reach critically low levels. Targets vary by context: maintain fibrinogen >1.5 g/L in major haemorrhage and >2.0 g/L in obstetric haemorrhage, where low fibrinogen predicts severe progression. Fibrinogen concentrate is an alternative in some centres, offering standardised dosing and rapid reconstitution.

Prothrombin complex concentrate contains vitamin K-dependent factors, especially II, IX and X, with variable factor VII depending on preparation. Four-factor PCC is preferred for urgent warfarin reversal with major bleeding or emergency surgery, given with intravenous vitamin K; dosing is often weight- and INR-based, commonly 25–50 IU/kg. It is not a substitute for plasma in global factor depletion unrelated to vitamin K antagonism unless specifically indicated.

Special products and modifications

Irradiated red cells and platelets are indicated for congenital cellular immunodeficiency, Hodgkin lymphoma, purine analogue or alemtuzumab exposure, intrauterine transfusion and donations from first- or second-degree relatives. Irradiation shortens red cell shelf-life and increases extracellular potassium, relevant in neonates and large-volume transfusion. Washed red cells or platelets are used for recurrent severe allergic reactions or anti-IgA-associated anaphylaxis. Granulocyte transfusions are rarely used, reserved for life-threatening infection with profound neutropenia or neutrophil dysfunction unresponsive to antimicrobials and expected marrow recovery.

Cross-Matching

Cross-matching is the final laboratory compatibility process intended to prevent transfusion of red cells carrying antigens against which the recipient has clinically significant antibodies. In modern practice it sits within a broader pre-transfusion compatibility pathway: unequivocal patient identification, ABO/RhD grouping, antibody screening, antibody identification where positive, selection of antigen-negative units, and either serological or electronic issue. Most catastrophic haemolytic transfusion events arise not from failure of immunohaematology but from wrong blood in tube or bedside misidentification; hence the emphasis in UK practice on two independent patient identifiers and, for first-time patients without a historical group, a second independently collected sample before non-emergency ABO-compatible red cells are issued.

Immunohaematological basis

The most clinically important incompatibility is ABO mismatch. Naturally occurring anti-A and anti-B are predominantly IgM, fix complement efficiently, and may cause rapid intravascular haemolysis. Rh, Kell, Duffy, Kidd and MNS antibodies are usually IgG, react optimally at 37°C, cross the placenta, and are detected by the indirect antiglobulin test (IAT). The IAT incubates patient plasma with reagent or donor red cells; after washing, antihuman globulin is added to bridge IgG-coated cells or complement-coated cells, producing visible agglutination. Enhancement media such as low ionic strength solution and polyethylene glycol accelerate antibody uptake and improve sensitivity. Clinically significant antibodies are those associated with haemolytic transfusion reactions or haemolytic disease of the fetus and newborn; examples include anti-D, anti-c, anti-E, anti-K, anti-Fya, anti-Jka and anti-S.

Group and screen, antibody identification, and unit selection

A group and screen determines ABO/RhD type and screens plasma against a panel, usually 2–3 reagent red cells expressing the major clinically relevant antigens. If the antibody screen is negative and there is no historical clinically significant antibody, red cells may usually be issued by electronic crossmatch where validated. If the screen is positive, antibody specificity must be identified using an extended panel, and units lacking the corresponding antigen are selected and crossmatched serologically. A patient with any historical clinically significant alloantibody should continue to receive antigen-negative blood even if the antibody is no longer detectable, because an anamnestic response may produce delayed haemolysis.

Stage	Purpose	Key examination points
ABO/RhD group	Defines essential compatibility	ABO-incompatible red cell transfusion is the classic cause of fatal acute haemolysis; RhD-negative patients should receive RhD-negative red cells where feasible.
Antibody screen	Detects unexpected alloantibodies	Performed at 37°C using IAT; positive screen mandates antibody identification and antigen-negative units.
Crossmatch	Tests patient plasma against donor red cells or validates electronic compatibility	Does not compensate for wrong sample labelling or failure of bedside checks.

Types of crossmatch

Method	Principle	Use	Limitations
Immediate-spin crossmatch	Recipient plasma and donor red cells mixed at room temperature, centrifuged, inspected for agglutination	Primarily detects ABO incompatibility	Does not reliably detect IgG antibodies reacting only at 37°C; largely superseded where electronic systems exist.
IAT/AHG crossmatch	Donor red cells incubated with recipient plasma at 37°C, washed, then antihuman globulin added	Required when antibody screen is positive, there is historical alloantibody, recent incompatible history, or electronic issue is not permitted	Takes longer, commonly 30–60 minutes once suitable units are available; may be delayed substantially if rare antigen-negative units are needed.
Electronic crossmatch	Computer algorithm confirms ABO/RhD compatibility using validated laboratory information system and negative antibody screen	Routine issue in low-risk patients with current negative antibody screen and no historical clinically significant antibodies	Requires robust IT validation, two determinations of ABO group according to local policy, and complete transfusion history.

The traditional terms major and minor crossmatch are still examinable. The major crossmatch tests recipient plasma against donor red cells and remains the clinically relevant red cell compatibility test. The minor crossmatch tested donor plasma against recipient red cells; it is not routinely performed for red cell components because donor plasma volume is small and components are separated, but donor plasma antibodies remain relevant for plasma-rich products.

Sample validity and timing

Compatibility samples must be current because alloantibodies may appear rapidly after antigen exposure. If the patient has been transfused or pregnant within the preceding 3 months, most UK and international guidance limits sample validity to 72 hours from collection. In patients without recent transfusion or pregnancy, longer validity may be permitted by local policy, often up to 7 days. Elective surgery commonly uses a maximum surgical blood ordering schedule; efficient systems aim for a crossmatch-to-transfusion ratio below approximately 2:1, reducing wastage while maintaining safety.

Emergency compatibility

In life-threatening haemorrhage, transfusion must not be delayed for full compatibility testing. If no group is available, emergency group O red cells are issued: O RhD-negative for females of childbearing potential and children where stock allows; many protocols use O RhD-positive for adult males and post-menopausal females to preserve O-negative inventory. Once ABO/RhD grouping is complete, group-specific uncrossmatched blood may be issued, followed by fully crossmatched units when available. A pre-transfusion sample should be taken before emergency blood is infused, as transfused donor cells may complicate subsequent serology.

Special compatibility considerations

• Females of childbearing potential: avoid RhD sensitisation and, where possible, provide Kell-negative red cells, as anti-K may cause severe fetal anaemia by erythroid suppression.
• Chronically transfused patients: extended phenotype or genotype matching for Rh variants and Kell, and sometimes Duffy/Kidd/MNS, reduces alloimmunisation, especially in sickle cell disease and thalassaemia.
• Autoimmune haemolytic anaemia: warm autoantibodies may make all units serologically incompatible; transfusion decisions rely on excluding underlying alloantibodies and providing the least incompatible, phenotype-matched blood when clinically necessary.
• Massive transfusion: after replacement of approximately one blood volume, serological findings may reflect donor cells and dilution; nevertheless, compatibility testing should continue and historical antibodies must be honoured.

For MRCP purposes, the key discriminator is that a negative crossmatch does not guarantee transfusion safety: it excludes detectable serological incompatibility under test conditions, but it cannot prevent clerical error, bacterial contamination, non-immune reactions, or antibodies below detection thresholds that later produce an anamnestic response.

Transfusion Reactions

Classification and immediate approach

Transfusion reactions are conventionally classified by timing (acute: during or within 24 hours; delayed: >24 hours to weeks) and mechanism (immune, non-immune, infectious, metabolic). In examination scenarios, any new fever, rigors, dyspnoea, hypotension, pain, urticaria, haemoglobinuria or bleeding during transfusion is a reaction until proven otherwise.

1. Stop the transfusion immediately; maintain intravenous access with 0.9% saline using a new giving set.
2. Assess airway, breathing, circulation; check observations including temperature, oxygen saturation and urine output.
3. Reconfirm patient identity against wristband, compatibility label and prescription.
4. Inform the transfusion laboratory and senior clinician; return the implicated unit and giving set.
5. Send post-reaction bloods: FBC, U&E, LFT, coagulation, group and screen, direct antiglobulin test, plasma free haemoglobin, bilirubin, LDH, haptoglobin; blood cultures if febrile or septic.

Major acute transfusion reactions

Reaction	Mechanism	Key clinical features	Management points
Acute haemolytic transfusion reaction	Usually ABO incompatibility causing complement-mediated intravascular haemolysis; most often clerical/sample error.	Fever, rigors, loin/back pain, chest pain, hypotension, haemoglobinuria, DIC, AKI; may present as unexplained bleeding under anaesthesia.	Stop transfusion; aggressive supportive care, 0.9% saline, maintain urine output approximately >0.5–1 mL/kg/hour; treat shock and DIC. Avoid empiric diuretics before adequate intravascular filling.
Febrile non-haemolytic transfusion reaction	Recipient antibodies to donor leucocytes or cytokines accumulated during storage; reduced by universal leucodepletion.	Temperature rise ≥1°C, chills/rigors without haemolysis or sepsis.	Exclude haemolysis and bacterial contamination. Paracetamol may be used; routine prophylaxis is not recommended.
Allergic/anaphylactic reaction	Hypersensitivity to donor plasma proteins; severe reactions classically in IgA deficiency with anti-IgA antibodies.	Urticaria/pruritus to bronchospasm, angio-oedema, hypotension and collapse.	Mild urticaria: antihistamine and may restart cautiously if symptoms resolve. Anaphylaxis: IM adrenaline 500 micrograms of 1:1000 in adults, repeat every 5 minutes as needed; oxygen, IV fluids, chlorphenamine and hydrocortisone adjunctively. Future transfusion may require washed cellular components.
TRALI	Non-cardiogenic pulmonary oedema due to donor anti-HLA/HNA antibodies or biological response modifiers causing neutrophil activation in pulmonary microvasculature.	Acute hypoxaemia and bilateral pulmonary infiltrates during or within 6 hours of transfusion; no circulatory overload.	Supportive oxygen/ventilation; avoid diuretics unless overload coexists. Plasma-rich components are typical triggers; risk reduced by male-predominant plasma policies.
TACO	Hydrostatic pulmonary oedema from excessive rate/volume relative to cardiac, renal or age-related reserve.	Dyspnoea, hypertension, raised JVP, pulmonary oedema, positive fluid balance, elevated BNP/NT-proBNP; usually within 6 hours.	Stop transfusion, sit upright, oxygen, IV furosemide commonly 20–40 mg in adults if not hypovolaemic. Prevention: single-unit transfusion policy, slow rate, pre-emptive diuretic in high-risk patients.
Bacterial contamination/septic reaction	Contaminated component; platelets higher risk because stored at 20–24°C.	High fever, rigors, hypotension, shock, DIC, often rapidly progressive.	Blood cultures from patient and component; broad-spectrum IV antibiotics immediately after cultures if possible; critical care support.

Distinguishing TRALI from TACO

This distinction is a common MRCP discriminator. Both cause acute respiratory deterioration after transfusion, but the haemodynamics differ. TRALI is permeability oedema: hypotension and fever are common, BNP is usually not markedly elevated, and echocardiography does not show fluid overload. TACO is circulatory overload: hypertension, raised venous pressure, S3 gallop, positive fluid balance and response to diuresis support the diagnosis. Modern haemovigilance definitions often use onset within 6 hours for both, so timing alone is insufficient.

Delayed reactions

Reaction	Timing	Mechanism and examination clues
Delayed haemolytic transfusion reaction	Typically 3–14 days	Anamnestic IgG response to red-cell antigens, especially Kidd, Rh, Duffy or Kell; extravascular haemolysis with falling Hb, jaundice, raised bilirubin/LDH and positive DAT. Kidd antibodies may become undetectable, explaining apparently compatible cross-match.
Post-transfusion purpura	5–10 days	Severe thrombocytopenia often <10 × 109/L due to alloantibody, classically anti-HPA-1a, destroying transfused and autologous platelets. Treat with IVIG 1 g/kg daily for 2 days; avoid platelet transfusion unless life-threatening bleeding.
Transfusion-associated graft-versus-host disease	4–30 days	Viable donor T lymphocytes engraft and attack host tissues; fever, rash, diarrhoea, hepatitis and marrow aplasia. Mortality >90%. Prevent with irradiated cellular components delivering approximately 25 Gy to the mid-plane.
Transfusion-transmitted infection	Days to years	Residual risks in developed systems are very low after donor selection and NAT screening, but bacterial platelet sepsis remains clinically important.
Iron overload	Chronic	Each red-cell unit contains approximately 200–250 mg iron; risk rises after repeated transfusion, particularly in marrow failure syndromes. Monitor ferritin and organ iron by MRI where relevant.

Metabolic and massive transfusion complications

Large-volume transfusion can produce hypocalcaemia from citrate binding, particularly with plasma and platelets or hepatic impairment; monitor ionised calcium and treat symptomatic hypocalcaemia with IV calcium gluconate. Hyperkalaemia may occur with older stored red cells, rapid transfusion, neonates or renal failure. Hypothermia worsens coagulopathy and arrhythmia risk; blood warmers are indicated for rapid transfusion, cold agglutinins or neonatal exchange. Dilutional coagulopathy and thrombocytopenia are managed using major haemorrhage protocols with laboratory or viscoelastic guidance.

Severity grading principles

Reactions are clinically graded by consequence: mild isolated urticaria or low-grade fever; moderate reactions requiring interruption and treatment; severe reactions causing hypoxia, hypotension, renal impairment, DIC, ICU admission or prolonged admission; and fatal reactions where transfusion is implicated. For MRCP, prioritise recognising ABO haemolysis, TRALI, TACO, anaphylaxis and bacterial sepsis, because immediate treatment differs and delay is dangerous.

Haemovigilance

Definition, scope and purpose

Haemovigilance is the structured surveillance of the entire transfusion chain, from donor selection and component manufacture to prescription, administration, monitoring and post-transfusion follow-up. Its purpose is not merely passive reporting but active risk reduction: detection of serious adverse reactions, identification of preventable system failures, denominator-based risk estimation, feedback into standards, and monitoring of corrective and preventive actions. In UK practice, haemovigilance is delivered through two complementary systems: statutory reporting to the MHRA via SABRE under the Blood Safety and Quality Regulations 2005, and confidential professional reporting to SHOT for learning and national benchmarking.

Regulatory architecture and traceability

Blood establishments and hospital transfusion laboratories must ensure full vein-to-vein traceability. For each component there must be documented linkage between donation number, processing history, issue, receipt, transfusion or final fate. Records must be retained for at least 30 years. This is central to donor look-back, recipient notification, recall of implicated components and investigation of transfusion-transmitted infection. Hospitals are expected to reconcile issued components, return unused units appropriately, and document transfusion start and completion, observations and adverse events.

System	Nature	Reportable events	Primary function
MHRA/SABRE	Statutory, regulatory	Serious adverse events affecting component quality/safety; serious adverse reactions causing death, life-threatening illness, disability, incapacity or prolonged hospitalisation	Legal compliance, inspection, enforcement and national safety regulation
SHOT	Confidential, professionally led	Adverse reactions, near misses, errors, delays, avoidable transfusion, transfusion-associated circulatory overload, transfusion-transmitted infection and component handling incidents	Education, system learning, benchmarking and national recommendations

Classification of haemovigilance events

Events should be classified by type, severity and imputability. Severity grading generally distinguishes non-severe morbidity, severe morbidity, life-threatening morbidity and death. Imputability assesses the probability that transfusion caused the event: excluded/unlikely, possible, probable/likely, certain, or not assessable. This distinction is crucial in examinations: a temporal association alone is insufficient; alternative explanations such as sepsis, cardiac failure, bleeding progression and drug reactions must be actively considered.

• Serious adverse reaction: an unintended response in donor or recipient associated with collection or transfusion that is fatal, life-threatening, disabling, incapacitating, or causes/prolongs hospitalisation.
• Serious adverse event: any untoward occurrence in collection, testing, processing, storage, distribution or issue that might affect component quality or safety.
• Near miss: an error detected before transfusion; these are highly valuable because they reveal system vulnerability without patient harm.
• Incorrect blood component transfused: includes ABO-incompatible transfusion, transfusion to the wrong patient, inappropriate component selection, failure of special requirements such as irradiated or CMV-negative components, and laboratory issue errors.

Key haemovigilance themes for MRCP

Modern UK haemovigilance repeatedly demonstrates that human factors and process failures, rather than intrinsic component defects, account for a large proportion of preventable harm. Errors cluster around patient identification, sample labelling, prescription, laboratory communication, collection from storage and bedside checking. “Wrong blood in tube” is particularly important because it may defeat subsequent compatibility testing; rates in observational systems are commonly of the order of 1 in 2,000 samples, though local rates vary with active surveillance intensity.

Among causes of transfusion-related death and major morbidity in high-income systems, transfusion-associated circulatory overload is consistently prominent, often exceeding classic immune complications such as haemolytic reactions or TRALI. Risk is highest in older patients, low body weight, renal impairment, cardiac dysfunction, hypoalbuminaemia, positive fluid balance and rapid multi-unit transfusion. Haemovigilance has therefore driven interventions such as single-unit red cell transfusion with reassessment, slower rates, pre-transfusion risk assessment, diuretic consideration, and avoidance of inappropriate transfusion.

Reporting thresholds and investigation

Any suspected serious reaction should trigger immediate clinical management and parallel haemovigilance actions: stop transfusion, maintain venous access, check patient identity and component compatibility, inform the transfusion laboratory, quarantine implicated units and giving sets, and obtain relevant samples. The laboratory investigation typically includes repeat ABO/RhD group, antibody screen, direct antiglobulin test, haemolysis markers, clerical audit and, where indicated, bacterial culture of patient and component. The haemovigilance report should state chronology, component type and volume, vital signs, differential diagnosis, treatment, outcome, severity and imputability.

Metric	Why it matters
Events per 100,000 components issued or transfused	Allows comparison across hospitals and over time; preferable to crude counts
Near misses per adverse event	High reporting may indicate a mature safety culture rather than poor practice
Time from event to reporting	Assesses responsiveness and supports timely recall/look-back
Completion of corrective and preventive actions	Determines whether learning has translated into risk reduction

Governance and prevention

Effective haemovigilance requires a hospital transfusion committee, transfusion practitioner input, competency-based training, electronic positive patient identification where available, robust policies for emergency release, major haemorrhage activation and special requirements, and regular audit against national standards. The most important conceptual point is that haemovigilance is a closed-loop safety system: detection, analysis, feedback, intervention and re-audit. For examination purposes, link haemovigilance to patient blood management, restrictive transfusion thresholds, single-unit policies and meticulous identification procedures; these are the interventions that convert surveillance data into reduced mortality and morbidity.