GC049 Fever After A Blood Transfusion
A febrile reaction occurring during or shortly after a blood transfusion, most commonly caused by recipient antibodies against donor leukocyte antigens or cytokines accumulated in stored blood products.
This lecture by Dr. YY Hwang (Haematology, QMH) is a critical GC lecture covering everything that can go wrong when you give someone blood products. The framing is clinical and practical: a patient on the ward spikes a fever mid-transfusion — what do you do? From that common scenario, the lecture radiates outward to cover all blood products, acute reactions (febrile, haemolytic, allergic, TRALI, TACO), delayed/chronic complications (delayed haemolytic reactions, TA-GVHD, iron overload, infections), massive transfusion complications, and prevention strategies including Patient Blood Management. [1]
Why this matters for exams: Transfusion reactions are a perennial SAQ/MCQ favourite. The 2025 Fourth Summative SAQ directly asked about risks and complications of blood transfusion and massive transfusion. [2] Past MCQs test irradiated blood products, CMV-negative products, and the distinction between TACO and TRALI. [3]
Learning Objectives (from the lecture): [1]
- Different kinds of blood products
- Acute adverse reactions after transfusion
- Chronic complications from transfusion
- How to prevent complications from transfusion
Blood products listed in the lecture: Red cells, Platelet concentrates, Fresh Frozen Plasma, Cryoprecipitate, Cryoprecipitate-reduced plasma, Leucocytes (buffy coat). [1]
| Product | Storage Temp | Shelf Life | Volume/Unit | Key Points |
|---|---|---|---|---|
| Packed Red Cells | 2–6°C (slide: 4°C) | Up to 42 days | ~330 mL | Anticoagulant-preservative/additive system varies by service |
| Platelet Concentrates | Room temp (20–24°C) | 4–5 days | Variable | Requires constant agitation; highest risk of bacterial contamination (stored at RT) |
| Fresh Frozen Plasma (FFP) | −30°C | Months (frozen) | ~250 mL | Contains ALL coagulation factors; must be thawed before use |
| Cryoprecipitate | −30°C | Months (frozen) | ~15–20 mL | Rich in fibrinogen, Factor VIII, vWF, Factor XIII |
| Granulocyte concentrate (slide: “leucocytes/buffy coat”) | 20–24°C | Transfuse as soon as possible (slide: 8 h) | Variable | Specialist component; must be irradiated |
The product photographs are also a practical recognition exercise: red cells are a dark red packed-cell bag; platelets are a smaller straw-yellow cellular suspension kept moving on an agitator; frozen plasma appears pale yellow and partly solid before thawing; and a granulocyte unit looks red because it contains substantial red-cell contamination. The printed ABO/Rh label, donation number, expiry and special-modification labels (for example, irradiated) must be checked rather than inferring compatibility from bag appearance.
Scope note: the volumes, shelf lives and temperatures above reproduce the 2022 Hong Kong slides. Component preparation and post-thaw expiry vary by blood service, so the unit label and local transfusion policy are authoritative. “Cryoprecipitate-reduced plasma” and “buffy-coat leucocytes” are service-specific/legacy terms rather than components a junior doctor should request without transfusion-medicine advice.
Why storage temperature matters: Platelets stored at room temperature support bacterial growth far more than red cells at 4°C — this is why bacterial contamination is most common in platelet transfusion. [1][4]
Why agitation matters for platelets: Gentle continuous agitation supports gas exchange and preserves platelet quality. The short shelf life further limits supply and increases wastage.
Why FFP must be thawed: Coagulation factors are preserved in the frozen state. Thawing introduces a clinically important delay in an emergency; the allowable post-thaw storage time is product- and service-specific.
FFP is the acellular component of blood — it contains no cells, only plasma proteins and all coagulation factors. [1]
High Yield: Platelet Contamination
Bacterial contamination is most strongly associated with platelet transfusion because platelets are stored at room temperature (20–24°C), which is permissive for bacterial growth. A cloudy, discoloured or clumped unit in the slide is a warning sign, but a contaminated unit can look normal: never use visual inspection to rule out sepsis. [1][4][10]
Historical opening image: why symptoms are not diagnoses
The deck recounts the 17th-century transfusion of calf blood to Antoine Mauroy: after a second exposure he developed fever, tachycardia, sweating, loin pain, nausea and dark urine — a pattern visually reminiscent of acute intravascular haemolysis. He later died, but the account also records arsenic poisoning by his wife. The teaching point is not that this proves a transfusion death; it is that the same visible syndrome can have competing causes, so a modern reaction must be stopped and investigated rather than labelled from one symptom.
The categories of risk from the lecture: Volume, Infections, Immunological, Electrolytes, Vascular, Iron load. [1]
This is a clean framework for any exam question asking "what are the risks of blood transfusion" — memorize these six categories.
Historical relative-risk graphic (Carson et al., NEJM 2017): the slide places HIV/HCV/HBV at the rare end; haemolytic reactions and TRALI in the middle; and FNHTR, allergic reactions and TACO at the more frequent end of a logarithmic axis, alongside everyday mortality comparisons. Read it as a relative-scale visual, not a source of current Hong Kong absolute risks: testing, component processing and surveillance definitions change over time. [1]
A patient receiving red cell transfusion develops a kick of fever, now 38.5°C, with half a unit remaining. Doctor, what should you do? [1]
This is the clinical anchor of the lecture. The three differential diagnoses for fever during/after transfusion are: [1]
- Infection — bacterial contamination of the blood product
- Haemolytic reaction — ABO incompatibility
- Febrile non-haemolytic transfusion reaction (FNHTR)
Immediate Management Algorithm (current safety framing) [1][4][5][10]
- STOP the transfusion immediately. Activate the rapid-response/emergency pathway if the patient is unstable.
- Assess ABC and monitor observations — temperature, pulse, BP, respiratory rate and oxygen saturation; give oxygen/resuscitation appropriate to the syndrome.
- Maintain IV access, but do not flush the implicated component through the existing line. Use a new line with 0.9% saline if ongoing access/resuscitation is required.
- Recheck identity and inspect the pack — wristband, compatibility label, prescription and unit number; look for clots, haemolysis, cloudiness, leaks or discolouration.
- Notify the responsible clinician and transfusion laboratory immediately. Preserve the bag and giving set; send these and fresh blood/urine samples exactly as local policy directs.
- Target the workup to severity: repeat group/screen and DAT; FBC/film, LDH, bilirubin, haptoglobin, electrolytes/creatinine and urinalysis; PT/aPTT/fibrinogen/D-dimer if severe; patient blood cultures and component culture when sepsis is possible.
- Do not restart a moderate/severe reaction or the implicated unit after suspected sepsis, haemolysis, anaphylaxis, TACO or TRALI. Restarting is considered only for a fully resolved isolated mild febrile or minor allergic reaction after serious causes have been excluded and a clinician/local protocol authorises it. [10]
Exam Tip: SAQ Management Steps
The management of acute transfusion reaction is a classic SAQ. The steps above (stop, vitals, recheck, save, workup) are the markscheme backbone. [5]
Acute Adverse Reactions: Detailed Breakdown
Usually a preventable wrong-blood event and potentially fatal. The slide's “always a medical error” refers specifically to transfusing ABO-incompatible red cells; AHTR can also be caused by non-ABO red-cell antibodies or non-immune haemolysis. [1][11]
Pathophysiology (from first principles): [1]
- Recipient has naturally occurring IgM and IgG anti-A and anti-B antibodies
- These are complement-fixing antibodies → when they bind transfused incompatible red cells, the classical complement pathway is activated → intravascular haemolysis
- Free haemoglobin released into plasma:
- Activates platelets
- Induces vascular inflammation
- Binds nitric oxide → causes smooth muscle dystonia (vasoconstriction/vasodilation disturbance)
- Complement activation liberates potent anaphylatoxins (C3a, C5a) → degranulates mast cells → histamine release → vasodilation, hypotension
- Cytokines released from phagocytes (TNF, IL-6, IL-8) → systemic inflammatory response
- Activates the coagulation system → DIC
Kidney injury is multifactorial: shock/hypoperfusion, renal vasoconstriction, DIC and haem-pigment tubular injury may coexist. The slide strongly emphasizes the haemodynamic and coagulopathic mechanisms; do not turn its “not free haemoglobin itself” wording into an absolute exclusion.
Clinical Features: [1]
- Abrupt onset of "sense of impending doom"
- Flushing, fever, rigors
- Loin/back pain (renal capsule distension from vasoconstriction)
- Vomiting, shock
- Haemoglobinuria ("coca-cola urine") [4]
- May develop DIC and acute renal failure
Management — current practice: [1][10][11][12]
- STOP the transfusion
- Urgent senior/haematology and critical-care input; support airway and blood pressure
- Use haemodynamically guided IV fluids and, where appropriate, a diuretic to maintain urine output while avoiding overload; monitor urine output, creatinine, potassium and coagulation
- Treat shock and DIC according to current institutional protocols; seek nephrology support if AKI progresses
- Do not restart the implicated unit or give further components until cleared by the transfusion service/haematologist
Historical correction: the 2022 slide lists alkaline diuresis and a dopamine infusion. These are not routine kidney-protective treatment. Current haemovigilance guidance focuses on stopping transfusion and supporting BP/urine output; KDIGO recommends against low-dose dopamine for prevention or treatment of AKI because it provides no renal benefit and may cause harm. [11][12]
Prevention: [1]
- ALWAYS do Type and Screen properly
- Give ABO-compatible blood; use emergency group O red cells when the group is unknown, then switch according to the transfusion laboratory/local policy
- This is a systems/human error — bedside identity checks are the final safety net
ABO-Incompatible Red Cells = Preventable Wrong-Blood Event
An ABO-incompatible red-cell transfusion usually reflects wrong patient identification, wrong sample/label, or wrong component selection and can be fatal. The safe rule is ABO-compatible, not “group-specific at all costs”: uncrossmatched group O red cells are deliberately used when life-threatening haemorrhage cannot wait for blood grouping. [1][13]
- Most common in platelet transfusion (room temperature storage) [1]
- Patient will be very septic, extremely ill [4]
- Common organisms: Pseudomonas fluorescens, Yersinia (psychrophilic organisms that can grow at 4°C in red cell units), Gram-negatives [5]
What to do: [1]
- Inspect the blood product for any visible damage or discolouration
- Microbiological workup of the patient (blood cultures from patient)
- Send the remaining blood product for culture + alert blood bank
- After cultures are obtained when feasible, start broad-spectrum IV antibiotics promptly if bacterial contamination is suspected; do not delay treatment in shock. [10]
Differentiating from other febrile reactions: high fever or a rise ≥1.5°C, rigors, tachycardia, BP change, respiratory distress, pain or nausea/vomiting are red flags for sepsis or haemolysis. A smaller isolated temperature rise may be FNHTR, but FNHTR is a diagnosis of exclusion and appearance alone cannot rule out a life-threatening reaction. [10]
Lecture-era incidence: Red cells 1–12.4%; platelets up to 30%. [1] These wide historical figures depend heavily on component processing and should not be quoted as a current local rate after modern prestorage leucoreduction.
Definition: Rise of body temperature by 1°C or more during or within several hours of transfusion. [1]
Mechanism: [1]
- Leucoagglutinins in the recipient bind to transfused leucocytes, activating monocytes → release of cytokines with pyrogenic properties
- Leucoagglutinins could be anti-HLA class I or granulocyte-specific antibodies
- Additionally, plasma factors (cytokines: TNF-α, IL-1α/β, IL-6) accumulate during storage in the blood bag
- Correlates with: number of residual leucocytes, storage time, storage temperature, rate of infusion
- Highest in platelet concentrates [1]
- Fever with chills/rigors and no evidence of haemolysis or infection
- Usually 30 min–2 hr after starting transfusion
- Mild fever, usually 1–2°C rise
- Dyspnoea, hypo/hypertension, shock or focal pain should trigger evaluation for a more serious diagnosis rather than being accepted as “just FNHTR.”
- FNHTR is the most common cause of transfusion fever
- Stop the unit first and exclude haemolysis, bacterial contamination, TRALI and other serious causes.
- Give an antipyretic for symptoms. A fully resolved, isolated mild reaction may be restarted slowly only after clinical review and according to local policy; moderate/severe reactions are not restarted.
- Prevention: leucocyte-reduced (leucodepleted) blood products
FNHTR: Most Common Cause of Post-Transfusion Fever
Incidence: mild allergic reactions 3%; anaphylaxis 1 in 20,000 transfusions. [1]
- Range from urticaria to anaphylaxis
- Allergic reactions towards transfused proteins
- Some are IgE-mediated; transfusion-associated allergic reactions have several possible plasma-protein/allergen mechanisms
- Severe reactions can occur in selected patients with IgA deficiency plus anti-IgA, or with antibodies to other plasma proteins such as haptoglobin. Most people with IgA deficiency do not have anti-IgA. [1][14]
IgA nuance: do not label every IgA-deficient patient as requiring special components. Anti-IgA testing is reserved for selected patients with an anaphylactic or recurrent severe allergic transfusion history. If IgA deficiency with anti-IgA is confirmed, a transfusion-medicine specialist may arrange washed red cells and/or IgA-deficient plasma/platelets. [14]
Management: Stop first. Isolated minor urticaria/pruritus → antihistamine; restart only after symptoms resolve, no systemic feature is present, and local policy/clinical review permits. Anaphylaxis → IM adrenaline immediately, oxygen/airway and IV-fluid support; antihistamines and corticosteroids are adjuncts, not substitutes for adrenaline. Consult transfusion medicine before future components. [10][14]
Hypotension and vasodilation due to reactions towards bradykinins or prekallikrein activator in plasma products. [1]
- Bedside filtration of blood products exposes plasma to charged synthetic surfaces → activates the contact pathway → generates bradykinin
- Mainly a concern in patients on ACEI — ACE normally degrades bradykinin, so patients on ACEI cannot clear the excess bradykinin → exaggerated hypotension [1]
This is a subtle but testable point. If an exam stem mentions a patient on ACEI developing isolated hypotension during transfusion without other features, think hypotensive transfusion reaction.
TACO was the leading pulmonary cause in the historical SHOT 2010–2017 chart shown in the deck. It remains a major cause of reported transfusion-related death, but surveillance rankings and rates vary by jurisdiction and year. [1][15]
The slide quotes 1–8% of transfusions. [1] Treat this as a broad lecture-era estimate rather than a current local incidence.
Why it happens: Blood products are essentially a volume load. If the patient's cardiovascular system cannot handle the extra volume (elderly, heart failure, renal impairment), they develop pulmonary oedema.
Reading the TACO radiograph in the slide: the chest film shows diffuse bilateral air-space oedema with an enlarged cardiac silhouette and vascular congestion. In practice, cardiomegaly, pleural effusions, raised JVP, hypertension/positive fluid balance and a raised NT-proBNP support hydrostatic overload, but no single sign is diagnostic.
At-risk groups: [1]
- Elderly
- Renal impairment
- Heart failure
Prevention (from the lecture): [1]
- Avoid unnecessary transfusion
- Transfuse ONE unit of red cells and reassess (restrictive approach)
- Control transfusion rate
- Judicious use of diuretics (e.g., furosemide between units)
- Close monitoring of haemodynamic and fluid status
FFP and TACO: [1]
- Plasma volume in adult ≈ 40 mL/kg
- To achieve haemostasis, 25–30% factor level is adequate → replacing 1/3 to 1/4 of plasma volume is enough
- Typical dose of FFP: 10–15 mL/kg → about 700–1,050 mL (roughly 3–4 × 250 mL units) in a 70 kg adult, not the “2 units” stated on the slide
- This represents a significant volume challenge
- Infusion rate and any prophylactic diuretic must be individualized to urgency, bleeding and TACO risk under local policy
Historical SHOT 2018 mortality data (from the lecture, not a current risk estimate): [1] Of 136 transfusion-related deaths (2010–2017):
- Pulmonary complications: 73 — of which TACO: 60, TAD (transfusion-associated dyspnoea): 8, TRALI: 5
- Delays: 31
- Other: 16 (includes 1 each of transfusion-transmitted infection, post-transfusion purpura, TA-GVHD, anti-D related event; 5 avoidable over-/under-transfusion; 7 unclassified)
- HTR: 11
- Febrile/allergic reactions: 5
In that 2010–2017 dataset, TACO accounted for 60/136 deaths (~44%). Do not transplant that percentage into a current consent discussion or use it as an individual patient's absolute risk.
Lecture-era incidence: 1 in 65,000 FFP infusions. [1] Incidence depends on case definition, component and haemovigilance system.
- Non-cardiogenic pulmonary oedema — this is what differentiates it from TACO
- Chills, fever, dyspnoea, and hypotension within 1–2 hours of transfusion
- Onset of respiratory distress defined to be within 6 hours of initiation of transfusion [1]
- Radiological evidence of new bilateral pulmonary infiltrates in the absence of circulatory overload
- Pathogenesis: donor anti-HLA/HNA antibodies can activate recipient neutrophils in the pulmonary microvasculature → endothelial damage and capillary leak, but demonstrable donor antibodies are not required for a clinical TRALI diagnosis
Reading the TRALI radiograph in the slide: it shows new, symmetric bilateral perihilar/basal air-space opacification without the obvious cardiomegaly seen on the TACO slide. The image communicates non-cardiogenic pulmonary oedema, but CXR alone cannot distinguish TRALI from TACO or ARDS; integrate haemodynamics, fluid balance, cardiac assessment and the 6-hour temporal relationship.
TACO vs TRALI — Critical Exam Discriminator:
| Feature | TACO | TRALI |
|---|---|---|
| Mechanism | Volume overload (cardiogenic) | Donor antibodies vs recipient WBCs (non-cardiogenic) |
| BNP/NT-proBNP | Often elevated | Often not elevated; overlap exists |
| JVP | Often raised | Usually not raised |
| CXR | Oedema; cardiomegaly/effusions may support TACO | Bilateral oedema without clear hydrostatic features |
| Timing | During or up to 12 h after (usually 1–2 h) | During or within 6 h |
| Response to diuretics | Usually improves | No expected benefit; may worsen hypovolaemia |
| Fluid balance | Positive | May be neutral |
| Blood pressure | Hypertension common | Hypotension common |
| Management | Diuretics, slow/stop transfusion | Supportive, ventilatory support |
Prevention of TRALI: plasma-risk-reduction policies may use male donors, never-pregnant female donors, or antibody-screened female donors. “Male-only FFP” is the simplified policy shown in the deck, not a universal bedside rule. [1]
Delayed / Subacute Adverse Reactions
Usually due to minor blood group incompatibility, e.g., Kidd antigen. [1]
Mechanism: [1]
- Initial antibody titre is too low to be detected in the T&S
- Transfusion of incompatible red cells provokes an anamnestic (memory) immune response
- Over days, antibody titre rises → sensitizes transfused RBCs → extravascular haemolysis (mainly in spleen)
- The slide highlights onset around 4–5 days; current haemovigilance definitions recognize DHTR from 24 hours to 28 days after red-cell transfusion. [6][16]
Clinical features: [1]
- Fever, jaundice, and rapid drop in Hb
- Often clinically silent (< 10% clinically diagnosed) [6]
- Haemolysis is mainly extravascular; haemoglobinuria is unusual but can occur, and severe DHTR is possible.
Investigations: [1]
- CBP, reticulocyte count, manual blood film
- Haptoglobin, methaemalbumin, direct/indirect bilirubin, LDH
- Direct antiglobulin test (DAT), Indirect antiglobulin test (IAT)
- Extended red cell phenotype (of pre-transfusion sample)
Management: Generally self-limiting. Avoid future transfusion with the implicated red cell antigen. [6]
Acute vs Delayed Haemolytic Reaction
Acute: often ABO incompatibility → complement-mediated intravascular haemolysis → haemoglobinuria, shock, DIC, renal failure. Delayed: non-ABO red-cell antibody (classically Kidd, also Duffy/Kell/MNS) → anamnestic response and mainly extravascular haemolysis → inadequate Hb increment, fever/jaundice and raised LDH 24 h–28 d later. [1][16]
Mortality: 90%. [1]
Mechanism: [1]
- Transfused allogeneic (donor) lymphocytes attack the recipient
- Causes marrow aplasia, diarrhoea, rash, and hepatitis
- 4 to 30 days after transfusion
Who is at risk: [1]
- Immunocompromised recipients: preterm infants, bone marrow transplant recipients, congenital immunodeficiency
- Immunocompetent recipients receiving blood from a donor who is HLA-homozygous at a locus shared with the recipient — the recipient's immune system fails to recognize the donor lymphocytes as foreign because they share one HLA haplotype, but the donor lymphocytes CAN recognize the recipient's "other" haplotype as foreign
Prevention: Irradiation of blood products — gamma irradiation (or X-irradiation) inactivates donor lymphocytes while preserving red cell and platelet function. [1]
Current correction: irradiation is for defined at-risk indications, not every immunocompromised patient. For example, HIV/AIDS alone and temporary viral T-cell suppression are not blanket indications under BSH guidance. Follow the Hong Kong/local transfusion service's current indication list. [17]
Indications for Irradiated Blood Products (from lecture slide): [1]
| Indication | Details |
|---|---|
| Intrauterine transfusion | Foetuses requiring intrauterine transfusion |
| Post-intrauterine transfusion neonates | Neonates who previously received intrauterine transfusion — irradiate top-up transfusions until 6 months of age |
| Severe congenital cellular immunodeficiency | All cellular blood components |
| Allogeneic haemopoietic stem cell transplant | All cellular blood components |
| Autologous HSCT / CAR T-cell therapy | From ≥ 7 days prior to harvest until 3 months post-transplant/therapy |
| Purine analogue drugs | e.g., fludarabine, cladribine, clofarabine, bendamustine — until 12 months after completion |
| Anti-T-cell treatment | e.g., ATG, alemtuzumab, other T-cell monoclonals (for aplastic anaemia or leukaemia) — from initiation until 12 months after completion |
| Transfusion from close relatives | HLA-haplotype sharing risk → always irradiate |
The indication names are high yield; the exact start/stop intervals in this table reproduce the 2022 Hong Kong slide and must be checked against current local policy for a real patient.
The slide states that life-saving transfusion should not be withheld if an irradiated component is unavailable. That is an exceptional, specialist risk decision, not permission to treat leucodepletion or “older blood” as equivalent: leucodepletion is not a substitute for irradiation in an at-risk recipient. Urgently involve the transfusion laboratory/haematologist and document any concessionary release. [17]
Past Paper: MCQ on Irradiated Blood Products
A 2023 MCQ asked: A post-allogeneic stem cell transplant patient needs transfusion. CMV seropositive but CMV antigen negative. What blood product? Answer: One unit of irradiated red cells (option C), because the stem-cell-transplant indication determines the need to prevent TA-GVHD; CMV-seronegative selection follows the separate local CMV policy. [3]
Massive Transfusion Complications
Massive transfusion = > 1 total blood volume in 24 hours (or > 10 units packed RBCs). [5]
Citrate is present in stored red cells as anticoagulant. [1]
- Massive rapid transfusion → citrate toxicity
- Risk is higher in infants and patients with liver impairment (liver metabolizes citrate)
- Citrate chelates calcium → lowers ionized calcium → QT prolongation and arrhythmia
- Monitor ionized calcium during major haemorrhage and replace calcium according to the local massive-transfusion protocol and repeat measurements. The slide's fixed “10 mL of 10% calcium gluconate per litre” is a historical rule of thumb, not a universal prescription. [18]
Potassium is released from red cells with storage. [1]
- The slide quotes ~10.2 mmol extracellular potassium in one 28-day unit; this is illustrative because the load varies by component, storage, irradiation, washing and infusion conditions
- Risk of hyperkalaemia in infants and patients with renal impairment [1]
Why potassium leaks with storage: During storage, reduced membrane-pump activity allows K⁺ to accumulate in the supernatant. Risk is driven by the delivered extracellular potassium concentration, infusion rate/route and patient size/renal handling; do not independently demand “fresh blood” for every neonate—component selection is indication- and service-specific.
| Complication | Mechanism | Risk Groups | Prevention/Treatment |
|---|---|---|---|
| Hypothermia | Cold blood infused rapidly | All massive transfusion | Blood warmer |
| Citrate toxicity | Citrate chelates Ca²⁺ → ↓iCa → hypotension/arrhythmia | Rapid transfusion, shock, impaired citrate clearance | Serial ionized Ca²⁺; protocol-guided calcium |
| Hyperkalaemia | K⁺ leaks from stored RBCs | Infants, renal impairment, rapid central infusion | Monitor K⁺/ECG; request an appropriate modified product only under transfusion-service guidance |
| Dilutional/consumptive coagulopathy | Haemorrhage plus factor/platelet dilution and consumption | Critical bleeding | Activate the local massive-haemorrhage protocol; repeat platelets, PT/aPTT, fibrinogen and/or viscoelastic testing |
Long-Term / Chronic Complications
The image collage deliberately spans viruses (HBV, HCV, HIV, HTLV, CMV, West Nile and Zika), parasites (malaria), bacteria such as Treponema pallidum, and prion disease (vCJD). It is a hazard map, not a current Hong Kong incidence chart: actual residual risks depend on local epidemiology, donor deferral, testing and component processing. [1]
Prevention: [1]
- Voluntary donation and donor deferral (screening questionnaires, travel history, risk behaviour)
- Pathogen reduction for components where a validated technology and local policy exist; no single process covers every component or transfusion-transmitted pathogen
- Nucleic acid testing (NAT) for HIV, HBV, HCV to shorten the "window period"
CMV specifically: [1]
- Prevention of transfusion-transmitted CMV infection — use of CMV-negative products
- Leucodepletion also reduces CMV risk (CMV resides in leucocytes)
- Irradiation prevents TA-GVHD but does not make a component CMV-safe; these modifications answer different questions.
Indications for CMV-negative cellular components shown in the 2022 Hong Kong slide: [1]
| Indication | Notes |
|---|---|
| Elective transfusions during pregnancy | Not during labour, delivery, miscarriage, or termination of pregnancy |
| CMV-antibody-negative recipients of allogeneic stem cell grafts | If unavailable, leucodepleted components may be substituted |
| Intrauterine transfusions | — |
| Neonates with birth weight < 1.5 kg | — |
In emergency situations where CMV-negative components are unavailable, life-saving transfusion should not be withheld — leucodepleted blood components can be used as an alternative. [1]
The exact groups requiring CMV-seronegative rather than leucodepleted components differ across jurisdictions and change over time; follow the current local blood-service policy rather than memorizing this 2022 table as universal.
1 unit of blood = 200 mg iron. Daily excretion of iron = 1 mg. [1]
This means the body has essentially no mechanism to actively excrete excess iron. A chronically transfused patient (e.g., thalassaemia major) accumulates iron relentlessly.
Consequences of iron overload: [1]
- Iron accumulation in liver → liver fibrosis and HCC
- Heart → heart failure
- Endocrine organs → diabetes mellitus
- Growth retardation and hypogonadism (pituitary gonadotroph iron deposition → hypogonadotrophic hypogonadism) [7]
The slide's four-quadrant diagram links site to consequence: myocardial iron → cardiomyopathy/heart failure; hepatic iron → fibrosis/cirrhosis and HCC risk; pancreatic iron → diabetes; pituitary/gonadal iron → impaired growth and hypogonadism. The adjacent steel-coil photograph is a visual mnemonic for the cumulative load: each red-cell unit adds about 200–250 mg of iron, while physiological iron excretion is minimal.
Monitoring: [1]
- Serum ferritin
- MRI T2 of liver and heart* (gold standard for quantifying organ iron)
- Liver biopsy (rarely needed now with MRI)
Treatment: Iron chelation therapy [1]
- Deferoxamine (subcutaneous/IV), deferasirox (oral), deferiprone (oral)
The safest transfusion is not to transfuse at all. [1]
The lecture lists these prevention strategies: [1]
- Voluntary donation, donor deferral and mandatory testing → reduce infection transmission risk
- Pathogen reduction for components where a validated technology and local policy exist; there is no single universal method covering every component/pathogen
- Prestorage leucocyte reduction (aim: < 0.5 × 10⁹ leucocytes per unit) → reduces FNHTR, CMV transmission, HLA alloimmunization
- Prefer standardized prestorage leucoreduction; bedside leucocyte filtration is a legacy/service-specific approach and is not equivalent to irradiation
- Do not give routine blanket paracetamol/antihistamine/steroid premedication: evidence is weak, and it may be considered case by case for recurrent reactions under specialist/local guidance [19]
- Plasma-donor risk reduction (for example male/never-pregnant or antibody-screened donors) → reduces TRALI risk
- Irradiation of cellular components for defined at-risk indications → prevents TA-GVHD; it is not required for every form of immunosuppression [17]
- Alternatives to allogeneic blood:
- Iron supplementation (treat iron deficiency before resorting to transfusion)
- Acellular volume replacement where indicated (usually crystalloids); this restores circulating volume but does not replace oxygen-carrying capacity, and colloids have their own indication-specific harms
Historical QMH trend chart (2017–2019): iron use rose while red-cell use fell. This is consistent with the first PBM pillar, but the dual-axis ecological chart has no comparator and does not prove that iron caused the reduction; changes in case mix, thresholds and other PBM measures could contribute. [1]
Patient Blood Management (PBM) — Three Pillars [1]
| Pillar | Strategy |
|---|---|
| 1st Pillar: Optimize Haematopoiesis | Treat iron/B12/folate deficiency, use EPO, address underlying cause of anaemia |
| 2nd Pillar: Minimize Blood Loss | Surgical haemostasis, cell salvage, antifibrinolytics (tranexamic acid), restrictive phlebotomy |
| 3rd Pillar: Optimize Patient-Specific Tolerance of Anaemia | Restrictive transfusion thresholds, optimize cardiopulmonary reserve, timely decision-making |
Patient Blood Management - Three Pillars
The three pillars of Patient Blood Management: (1) Optimize haematopoiesis, (2) Minimize blood loss, (3) Optimize patient-specific tolerance of anaemia. This is the modern framework to reduce unnecessary transfusion. "The safest transfusion is not to transfuse at all." [1]
The slide's PBM message is appropriate, but a haemoglobin number is a consideration, not an automatic prescription. Current AABB guidance states: [20][21]
- In most haemodynamically stable hospitalized adults, consider a restrictive strategy when Hb is < 7 g/dL, incorporating symptoms, active/ongoing bleeding, comorbidity, trajectory and patient preferences.
- Common trial thresholds include 7.5 g/dL after cardiac surgery and 8 g/dL after orthopaedic surgery or with pre-existing cardiovascular disease.
- Acute myocardial infarction is now a distinct exception: the 2025 AABB guideline conditionally favours a liberal strategy when Hb is < 10 g/dL, while emphasizing individual clinical context. Do not apply the older note's blanket “ACS 8–9” rule.
- These thresholds do not replace a major-haemorrhage protocol in haemodynamic instability, and they do not automatically apply to chronic transfusion-dependent anaemias.
The lecture/senior note describes a Hong Kong “type-and-screen” workflow. A compatible unit is still selected and checked: eligible patients with a negative screen may use validated electronic issue/crossmatch, whereas a positive antibody screen generally requires antibody identification, antigen-negative units and serological compatibility testing. [9]
| Step | What It Does | Why |
|---|---|---|
| Type | ABO and Rh typing of patient's red cells | Ensures group-compatible blood |
| Screen | Check patient's serum against panel of RBCs with known antigens by indirect Coombs test | Detects unexpected antibodies (e.g., anti-Kidd, anti-Duffy) |
| Compatibility/issue step | Electronic issue may be used when eligibility criteria are met; otherwise serological crossmatch | Confirms that the selected donor unit is appropriate; exact workflow is laboratory-specific |
- T&S is only valid for 3 days (new antibodies can form) [5][9]
- If screen is positive → "ALERT" symbol on blood bank system → additional testing needed before issuing RBCs [9]
| Reaction | Timing | Mechanism | Key Features | Management | Prevention |
|---|---|---|---|---|---|
| AHTR | Immediate (min–h) | Often ABO mismatch; complement-mediated intravascular haemolysis | Pain, shock, haemoglobinuria, DIC, AKI | Stop; urgent ABC/BP/renal support; specialist/ICU; do not restart | Compatibility + identity systems |
| Bacterial sepsis | During/immediately after | Contaminated product | Fever/rigors, tachycardia, hypotension/shock | Stop; cultures (patient + component); broad-spectrum IV antibiotics | Donor/processing controls; inspect pack (normal appearance does not exclude) |
| FNHTR | During–4 h | Recipient antibodies/cytokines; diagnosis of exclusion | Isolated fever (≥1°C), chills/rigors | Stop and exclude danger; antipyretic; restart only if mild, resolved and authorised | Prestorage leucoreduction |
| Allergic | During–4 h | Reaction to plasma proteins/allergens | Urticaria → anaphylaxis | Antihistamine if minor; IM adrenaline for anaphylaxis | Specialist-selected washed/IgA-deficient product for defined recurrent/severe cases |
| Hypotensive | During transfusion | Bradykinin (esp. ACEI patients) | Isolated hypotension | Stop; exclude other serious reactions; supportive care | Follow local policy; review the ACE-inhibitor/filter context with the transfusion service |
| TACO | During–12 h | Hydrostatic volume overload | APO, raised JVP, hypertension/positive balance, often ↑BNP | Stop; sit upright, oxygen, diuretics/cardiac support | Risk assess, slow rate, 1 unit then reassess; consider diuretic |
| TRALI | Within 6 h | Inflammatory non-cardiogenic lung injury; sometimes donor HLA/HNA Ab | Hypoxaemia + bilateral oedema without dominant overload | Stop; oxygen/ventilation; no routine diuresis | Plasma donor risk-reduction policy |
| DHTR | 24 h–28 d | Anamnestic non-ABO red-cell Ab, mainly extravascular haemolysis | Inadequate Hb rise, fever/jaundice, ↑LDH, +DAT | Supportive; antigen-negative blood if needed | Antibody history + phenotype/genotype matching where indicated |
| TA-GVHD | 4–30 days | Donor lymphocytes attack recipient | Rash, diarrhoea, hepatitis, marrow aplasia, 90% mortality | Largely untreatable | Irradiation |
| Haemosiderosis | Chronic | Iron accumulation (200mg/unit) | Heart failure, cirrhosis/HCC, DM, hypogonadism | Iron chelation | Minimize transfusion |
High Yield Summary
- Fever during transfusion
- Think infection (bacterial contamination), ABO haemolytic reaction, or FNHTR.
- Always stop, check identity, and work up.
- ABO-incompatible red-cell AHTR is usually a preventable wrong-blood event; stop and urgently support ABC, BP and renal perfusion. Do not use renal-dose dopamine.
- AKI in severe haemolysis is multifactorial: shock, vasoconstriction, DIC and haem-pigment injury can contribute.
- FNHTR is a diagnosis of exclusion; only a resolved isolated mild reaction may be restarted after clinical review/local authorisation.
- TACO dominated the historical SHOT pulmonary-mortality chart and remains a major preventable hazard; risk assess, transfuse slowly, and use one unit then reassess in stable non-bleeding adults.
- TRALI is non-cardiogenic pulmonary oedema within 6 hours; plasma-donor mitigation follows blood-service policy.
- TA-GVHD is usually fatal — prevent with irradiation for defined at-risk indications; leucodepletion is not a substitute.
- Massive transfusion complications: hypothermia, hypocalcaemia/citrate toxicity, potassium disturbance and coagulopathy — monitor serially and treat via the local protocol.
- Iron overload: 200 mg iron per unit, 1 mg/day excretion — monitor with ferritin and MRI T2*, treat with chelation.
- The safest transfusion is not to transfuse at all — Patient Blood Management: optimize haematopoiesis, minimize blood loss, optimize tolerance of anaemia.
Active Recall - Fever After a Blood Transfusion
[1] Lecture slides: GC 049. Fever after a blood transfusion.pdf (all pages) [2] Past papers: 2025 Fourth Summative SAQ.pdf (Q2, p4) [3] Past papers: 2023 Fourth Summative MCQ.pdf (Q45, p17) [4] Senior notes: Block A - Fever after a blood transfusion_ transfusion and related problems.pdf (pp1, 8, 9) [5] Senior notes: Maksim Medicine Notes.pdf (p184) [6] Senior notes: Ryan Ho Haemtology.pdf (p147) [7] Senior notes: Block A - I keep on bumping into people on my side_ pituitary tumours; hypopituitarism.pdf (p18) [8] Senior notes: Block A - Coffee ground vomitus tarry stool upper GI bleeding.pdf (pp13–14) [9] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf (pp24–25) [10] Australian Red Cross Lifeblood: Management of suspected transfusion reactions (updated October 2025) [11] Australian Red Cross Lifeblood: Acute haemolytic reactions (updated June 2026) [12] KDIGO: 2012 Clinical Practice Guideline for Acute Kidney Injury, recommendation 3.5.1 (do not use low-dose dopamine to prevent or treat AKI) [13] Australian Red Cross Lifeblood: Use of red cells [14] Australian Red Cross Lifeblood: Severe allergic reactions (updated June 2025) [15] Australian Red Cross Lifeblood: Transfusion-associated circulatory overload [16] Australian Red Cross Lifeblood: Delayed haemolytic transfusion reactions [17] British Society for Haematology: Guidelines on the use of irradiated blood components (2020) [18] Australian Red Cross Lifeblood: Massive transfusion complications [19] Canadian Blood Services: Transfusion reactions — Clinical Guide (2022) [20] AABB: Updates in Red Blood Cell Transfusion Thresholds (2023 international guideline summary) [21] AABB: Red-cell transfusion in acute myocardial infarction (2025 conditional recommendation)
GC048 Fever
Fever is an elevation of body temperature above the normal range, typically exceeding 38°C (100.4°F), resulting from a resetting of the hypothalamic thermoregulatory set point in response to pyrogenic stimuli.
GC050 Fever And A Murmur
A clinical presentation of fever accompanied by a cardiac murmur, raising concern for infective endocarditis until proven otherwise.