Mednotes

L2 Blood Blood transfusion 2

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aliasesL2 Blood Blood transfusion 2

14 min read

Overview

This lecture covers the safety side of blood transfusion: how donors are selected and screened, which transfusion-transmitted infectious diseases (TTID) are tested for and why, how leucodepletion reduces risk, and the spectrum of transfusion reactions (from common/mild to rare/serious) including their recognition, causes and prevention.

Donor selection

First principle: do no harm to donors or patients.

  • Whole blood donors can donate 450 mL at 3-monthly intervals; fewer donations recommended for menstruating women.
  • Eligibility criteria:
    • Age 16-70 (new donors) or 16-80 (repeat donors).
    • Weight ≥50 kg and height ≥150 cm.
    • Haemoglobin ≥120 g/L (females), ≥130 g/L (males).
    • In general good health, assessed by questionnaire.
    • Not pregnant in the last 9 months.

Sexual activity screening changes

  • NZBS moved to “individualized donor assessment”: all donors, regardless of gender, are asked the same questions about sexual activity, and the men-who-have-sex-with-men-specific questions have been retired.
  • New questions (all genders): new or multiple sexual partners in the past 3 months, and anal sex with any of these partners. If YES to both, defer for 3 months.
  • Impact: eligibility of gay and bisexual men rose from 13% (old rules) to 41% (new rules). Framed as a fairer assessment: accurately identifies high-risk donors, avoids excluding low-risk donors, and bases decisions on risk rather than identity.

Testing blood donors

Every unit of blood is tested for:

  • ABO and RhD blood groups.
  • Unexpected red cell antibodies.
  • Transfusion-transmitted infectious diseases (TTID).
  • Other tests as required.

Other, situational testing examples:

  • Malaria testing for donors who have travelled to a malaria-endemic area.
  • CMV antibody testing on components for at-risk patients.
  • Extended red cell phenotyping to stock units for patients with unexpected antibodies.
  • Ferritin testing for donors failing the screening haemoglobin test.

Transfusion-transmitted infectious diseases (TTID)

Bacteria, viruses, parasites and prions can be transmitted via red cells, plasma and platelet donations. All NZ donors are tested at every donation for:

  • HIV (antibody/antigen and Nucleic Acid Testing, NAT)
  • Hepatitis A (NAT)
  • Hepatitis B (HBsAg and NAT)
  • Hepatitis C (anti-HCV and NAT)
  • Syphilis (anti-Treponema pallidum testing)
  • Parvovirus B19 (NAT)

The agents

  • HIV: a retrovirus; possesses reverse transcriptase, allowing it to make a DNA copy of its RNA genome. Bloodborne; transmitted by sexual contact (heterosexual and homosexual), infected blood or blood products, artificial insemination with infected semen, shared infected needles, or mother to unborn baby.
  • Hepatitis A (HAV): waterborne DNA virus; blood transmission is rarer.
  • Hepatitis B (HBV): bloodborne DNA virus. 2% of the NZ population carry HBV. Can progress to chronic hepatitis and liver cancer. Presence of hepatitis B surface antigen (HBsAg) indicates acute HBV infection.
  • Hepatitis C (HCV): RNA bloodborne virus. 1% of New Zealanders are HCV positive. Historically harder to treat than HBV, but new drugs can now eliminate it. Presence of anti-HCV or HCV RNA in plasma is diagnostic.
  • Syphilis: caused by the bacterial spirochete Treponema pallidum. Treponemes can survive in refrigerated stored red cells for up to 120 hours. Cases are increasing in all age groups in NZ.
  • Parvovirus B19: mostly causes disease in children (classic cause of fifth disease, a childhood rash). A risk for pregnancy and immunocompromised patients. Spreads respiratorily as well as by blood.

Historical context and current risk

The 2022 BBC report “1 in 3 infected with HIV in blood scandal was a child” (UK contaminated blood inquiry) is cited as a past tragedy motivating current screening rigour.

Since the 1980s, risk per unit for HCV, HBV and HIV has fallen steeply (log scale, roughly 1:100 down to about 1:1,000,000) as successive interventions were introduced: revised donor deferral criteria (pre-1984), HBsAg screening (1984), HIV antibody screening (1986), NANB hepatitis surrogate testing, HCV antibody screening (1990), p24 antigen testing (1996), HCV and HIV NAT (1998-2000), vCJD deferral criteria, WNV NAT (2002), T. cruzi antibody screening, and HBV NAT (2008-2010). Over the same period, new emerging infectious threats have continued to appear (e.g. ICL, bacteria, vCJD, Trypanosoma cruzi, PTLVs, SFV, WNV, SARS, monkeypox, leishmania, influenza, DENV, rubella, CHIKV, XMRV).

NZ’s blood supply is considered one of the safest in the world. Current risk of acquiring a viral infection from transfusion in NZ (NZBS, February 2023):

  • HIV: 1 in 13.48 million
  • HCV: 1 in 9.97 million
  • HBV: 1 in 1.1 million

Minimising the risk of TTID

In addition to testing, NZBS uses:

  • No financial incentives to donate.
  • A donor eligibility quiz and detailed questionnaire (e.g. asking about recent tattoos/piercings, which can trigger a deferral, such as a 3-month wait, or only 12 hours if performed by a registered health professional).
  • Donor deferral, both self-deferral and deferral by NZBS.
  • Self-sufficiency: NZ donations used for NZ patients wherever possible.

Pre-storage leucodepletion

All blood components (red cells, plasma, platelets) are depleted of white cells before storage, reducing white cell count to very low levels, achieved by filtration.

Process flow: Whole blood → filtration → leucodepleted whole blood → centrifugation → splits into red cells and plasma. Red cells are combined with resuspending fluid to give resuspended red cells; plasma becomes fresh frozen plasma.

Why leucodeplete?

Known benefits:

  • Reduces non-haemolytic febrile transfusion reactions caused by leucocyte antibody-antigen reactions.
  • Reduces alloimmunisation to leucocyte antigens.
  • Reduces risk of cytomegalovirus (CMV) transmission.
  • Reduces platelet refractoriness.

Postulated benefits:

  • Reduces other infections where infectious agents reside in white cells (e.g. HTLV, bacteria).
  • Reduces Transfusion Related Immunomodulation (TRIM).

Transfusion reactions: overview

Reactions are grouped by frequency and severity:

  • Infrequent, but serious: ABO incompatible transfusion, Transfusion Related Acute Lung Injury (TRALI), anaphylactic reactions, TTID.
  • Common, but less serious: febrile non-haemolytic transfusion reaction (FNHTR), mild allergic reactions.
  • Serious, and too common: Transfusion Associated Circulatory Overload (TACO).

Recognising and responding to acute reactions

Approach: Recognise. Respond. Report.

When a patient shows signs/symptoms suggestive of a potential transfusion reaction:

  1. STOP the transfusion immediately.
  2. Assess: rapid clinical assessment.
  3. Check: confirm the patient’s ID band matches the blood unit label details. [flag: word illegible in source — possibly “bag” or “unit”]
  4. Inspect: visual check of the unit for turbidity, clots or abnormal appearance.
  5. Talk with the patient: establish status, inform and comfort.

An ATR (Acute Transfusion Reaction) Notification to Blood Bank form is used to report reactions, recording patient identifiers, whether the patient was under general anaesthesia/ventilated, transfusion timing, volume transfused, the implicated unit number(s), and which blood component was administered (red cells, fresh frozen plasma, platelets, cryoprecipitate, or other, with a separate form 111F003 for fractionated plasma products such as IVIg).

ABO incompatible transfusion

Results from error(s), most commonly Wrong Blood in Tube (WBIT): blood collected from one individual but labelled with another individual’s identifying details. Consequences can include non-indicated treatment, lack of treatment, or an incompatible blood transfusion. 43 WBIT incidents were detected around New Zealand in 2021.

Case example (2022 Annual Report, AHTR/IBCT): an 84-year-old O RhD-positive man admitted with sepsis, for whom blood was not required or prescribed, was given approximately 100 mL of a unit of A RhD-negative red cells intended for another patient in the same room. He developed abdominal pain and hypertension, was transferred to ICU, and subsequently developed dark urine, a positive direct antiglobulin test, and haemolysed blood samples. He was recovering and had been transferred to a medical ward at the time of reporting.

The lecture also references an educational case (“Strange Case of Penny Allison,” a UK Blood Transfusion Service video) and draws an analogy between distraction while transfusing and distraction while driving (a driver is four times more likely to have an accident while on a mobile phone, as it is hard to concentrate on two things at once).

TACO (Transfusion Associated Circulatory Overload)

  • Acute pulmonary oedema occurring within 12 hours of transfusion, resulting from volume overload.
  • 8 deaths from TACO over a 9-year period (2013-2022).
  • TACO accounts for 72% of all fatalities resulting from blood transfusion.
  • Higher-risk patients: age greater than 60, small body size, compensated cardiac dysfunction, chronic renal failure.
  • The reported annual rate of TACO reactions (per 10,000 units transfused, with 95% CI) fluctuated around a baseline near 1.5 from 2013-2021 (with a low around 0.7-0.9 near 2016-2017), then rose sharply to approximately 2.3 in 2022 with a wide confidence interval. [flag: the source page also contains the text “Non-severe / Severe / Life-threatening / Death” per a cross-check against extracted text, but this severity-scale labelling was not clearly legible in the rendered image]

TACO prevention

  • Single unit transfusion.
  • Choose the right blood component or alternative for the patient.
  • Monitor fluid balance and patient signs/symptoms during transfusion.
  • Slow the transfusion.
  • Prophylactic diuretics.
  • New acute lung injury occurring within 6 hours of transfusion.
  • Caused by HLA or neutrophil antibodies in the donor; these antibodies bind to the patient’s white cells, which then adhere to pulmonary epithelium and initiate an inflammatory response.
  • One case in 2021, zero in 2022; cases have been reducing over the years due to practice changes including collecting plasma only from male donors and screening donors for HLA antibodies.

FNHTR (Febrile Non-Haemolytic Transfusion Reaction)

  • A common reaction, though less common since leucodepletion was introduced.
  • Occurs when the patient has a white cell antibody that reacts with residual white cells in the blood component.
  • Usually not severe.

Allergic reactions and anaphylaxis

Mild allergic reactions:

  • Common, presenting with urticaria and itching.
  • A type 1 hypersensitivity immune response to an allergen in the donation.

Anaphylaxis:

  • Rare.
  • The allergic reaction progresses to a life-threatening state.
  • Associated with patients who have protein deficiencies and a corresponding antibody, for example patients with IgA deficiency and anti-IgA reacting to IgA present in donor plasma (and red cells).

2022 adverse transfusion reaction data (by type and severity)

NZBS 2022 data (Grade 1 / Grade 2 / Grade 3 / Grade 4 / Total):

  • FNHTR: 135 / 14 / - / - / 149
  • Allergic: 66 / 6 / 3 / - / 75
  • TACO: 13 / 17 / 2 / - / 32
  • DSTR: 30 / 1 / - / - / 31
  • TAD: 12 / 3 / - / - / 15
  • UCT: 12 / 3 / - / - / 15
  • TAH: 5 / 3 / - / - / 8
  • AHTR: 1 / - / 1 / - / 2
  • Total: 274 / 47 / 6 / - / 327 (83.8% / 14.4% / 1.8% / - of all reactions)

NZBS (ISBT) severity grade definitions:

  • Grade 1, Non-severe: the recipient may have required treatment, but lack of treatment would not have caused permanent damage or impairment of a body function.
  • Grade 2, Severe: required hospitalisation or prolonged hospitalisation directly attributable to the event, and/or resulted in persistent or significant disability/incapacity, or required medical/surgical intervention to prevent permanent damage or impairment of a body function.
  • Grade 3, Life-threatening: required major intervention following transfusion (e.g. vasopressors, intubation, transfer to intensive care) to prevent death.
  • Grade 4, Death: the recipient died following an adverse transfusion reaction, and death is probably or definitely related to the transfusion (if the patient died of another cause, the event is graded 1, 2 or 3 instead).

Self-test

  1. List the donor eligibility criteria for age, weight, height and haemoglobin level for whole blood donation.
  2. Describe how NZBS’s sexual activity screening approach changed, and what the new questions ask.
  3. List the four categories of tests performed on every unit of donated blood.
  4. Distinguish HBV from HCV in terms of genome type, population prevalence in NZ, and the diagnostic marker used for each.
  5. Explain why syphilis remains a transfusion risk despite refrigerated storage of red cells.
  6. List four measures NZBS uses (beyond laboratory testing) to minimise the risk of transfusion-transmitted infectious disease.
  7. Describe the process of pre-storage leucodepletion, from whole blood to its final components.
  8. List the known benefits of leucodepletion.
  9. Describe the five steps to take when a patient shows signs or symptoms suggestive of a transfusion reaction.
  10. What is Wrong Blood in Tube (WBIT), and what consequences can it cause?
  11. Define TACO, including its typical time of onset and underlying mechanism, and list two patient groups at higher risk.
  12. List two measures used to prevent TACO.
  13. Describe the mechanism of TRALI and explain why its incidence has fallen in recent years.
  14. Distinguish FNHTR from mild allergic transfusion reactions in terms of underlying mechanism.
  15. Explain why patients with IgA deficiency are at particular risk of anaphylaxis during transfusion.
  16. A 65-year-old man with chronic renal failure develops acute breathlessness and hypertension 8 hours after a red cell transfusion. Which reaction is most likely, and what features point to it?

Answers

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