Transfusion Reactions

Adverse reactions to allogenic blood can be classified by:

Reactions specific to infusion of vast volumes of blood product are covered under Critical Bleeding.

• Immunological vs. non-immunological
• Acute vs. delayed

As patients receiving blood transfusion are typically unwell, there can be uncertainty as to whether the deterioration was caused by transfusion or incidental to it.

Complications likely to be multifactorial include:

• ARDS
• Storage lesions
• VTE
• TACO
• TRALI
• CMV infection

Classification of Transfusion Reactions

	Immunological	Non-Immunological
Acute	ABO mismatch Rapid intravascular haemolysis. Acute haemolysis Type II hypersensitivity. Anaphylaxis Type I hypersensitivity. TRALI Febrile, non-haemolytic Mild, benign ≥1ºC temperature ↑. Acute haemolysis should be excluded. Urticaria	TACO Cardiac failure due to ↑ intravascular blood volume. Non-immune mediated haemolysis Physicochemical RBC destruction. Infections Massive transfusion complications Air embolism Hypothermia ↑ K+ ↓ Citrate Causing: ↓ Mg2+ ↓ Ca2+
Delayed	Delayed haemolysis Sensitisation 2-14 days after exposure, typically to minor antibodies. Transfusion-Associated GvHD Infused lymphocytes attack a (usually) immunocompromised host. Alloimmunisation Transfusion-related Immune Modulation Generalised immunosuppression occurring post allogenic transfusion. Post-transfusion purpura	Iron overload

Acute Immunological

Fever

Mild fevers are common (~1%) and unconcerning.

Acute Haemolysis

Features:

The most severe form of acute haemolytic reactions are due to ABO incompatibility.

• Anaemia
  • Pain
    Including ischaemia.
  • Nausea, vomiting
  • Shock
• Immune activation
  • Rigors
  • Hypotension → Shock → Circulatory collapse
• AKI
  • Pre-renal due to volume loss
  • Intra-renal due to myoglobinuria
• Coagulopathy
  May be identified by worsening of existing bleeding despite transfusion.

Hypersensitivity Reactions

Blood (particularly non-cellular blood) contains large numbers of potentially antigenic compounds. Reactions may occur due to donor product:

• Antigen
  Recipient reacts to donor antigens.
• Antibody
  Donor antibodies react with recipient blood or plasma proteins.
• Contaminants
  Including:
  • Chemical additives
  • Medications
    Recipient allergy to medication in donor sample.
  • Microorganisms

Features are consistent with hypersensitivity reactions, and include:

Features and management of severe hypersensitivity reactions are covered in more detail under Anaphylaxis.

• Skin manifestations
  • Rash
• Gastrointestinal distress
• Hypotension
• Bronchospasm
• Arrest
  Cardiac or respiratory.

Transfusion Related Acute lung Injury

TRALI is defined as acute respiratory distress that:

• Occurs within 6 hours of transfusion
• Results in hypoxaemia
• Does not have another course

TRALI is:

• Characterised by:
  • Fever
  • Haemodynamic lability
  • Dyspnoea
  • Hypoxaemia
• Due to interstitial oedema, generally lasting <48 hours
• The major cause of transfusion-related mortality
• Due to leukoagglutininins in donor plasma promoting neutrophil activation
  • Neutrophils are sequestered in lung microcirculation
    • Subsequent endothelial injury and activation ↑ degree of sequestration
      More common in:
      • Critically ill
      • Smokers
      • Shock states
      • High ventilator pressures
  • Leukoagglutinins are also more common in multiparous women

Delayed Immunological

Transfusion-Associated Graft-Versus-Host Disease

Classically an immunocompromised recipient displays:

GvHD is covered in detail under Graft versus Host Disease.

• 3-30 days following transfusion
• ↓ Risk with treating blood products to neutralise lymphocytes:
  • Leukoreduction
  • Gamma irradiation

Acute Non-Immunological

Infections

Bacterial:

• Rapid occurrence of septic shock
• More likely with platelet transfusion due to room-temperature storage

CMV:

Blood film expected to show atypical lymphocytes with ↑ cytoplasm (hence the name CMV, irregular contours of the nucleus, and intranuclear inclusions.

• Suggested by:
  • Swinging fevers
  • Mononucleotic blood film
  • 7-10 days post transfusion
• Rarely significant outside of immunocompromised patients

HIV and Hepatitis:

• Post-transfusion hepatitis and HIV are potential complications
• Extensive donor selection and testing excludes infective donors
• HIV and Hepatitis B and C are almost totally preventable transfusion-transmitted disease

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References

1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.