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Transfusion reaction

Transfusion reactions may occur during blood transfusion. Most commonly caused by clerical errors, like giving the blood to the wrong patient, drawing the wrong blood specimen, failing proper patient identification, wrong labelling, performing the ABO test wrong, etc. Some are mild, some are life-threatening.

Classification of reactions

According to pathomechanism:

  • Immune-related complications
    • Antigen-antibody-mediated reactions
      • Acute haemolytic transfusion reaction
      • Delayed haemolytic transfusion reaction
      • Post-transfusion purpura
      • Transfusion-related acute lung injury (TRALI)
      • Anaphylaxis
    • Immune cell-mediated reactions
      • Transfusion-associated graft-versus-host disease (TA-GVHD)
      • Transfusion-related immunomodulation (TRIM)
  • Non-immune-related complications
    • Transfusion-related circulatory overload (TACO)
    • Transfusion of infected blood – sepsis
    • Hypothermia due to cold blood transfusion
    • Massive transfusion syndrome
    • Transfusion of haemolytic blood
    • Air embolism
    • Citrate intoxication – hypocalcaemia
    • Transfusion of hyperkalaemic blood
    • Haemosiderosis
    • Thromboembolism

According to timeline:

  • Immediate complications (0 – 15 minutes)
    • Acute haemolytic transfusion reaction
    • Anaphylaxis
    • Air embolism
  • Early complications (15 minutes – 24 hours)
    • Transfusion-related circulatory overload (TACO)
    • Citrate intoxication – hypocalcaemia
    • Transfusion of infected blood – sepsis
    • Hypothermia due to cold blood transfusion
    • Thromboembolism
  • Late complications (1 – 7 days after transfusion)
    • Transfusion-associated graft-versus-host disease (TA-GVHD)
    • Delayed haemolytic transfusion reaction
  • Very late complications (weeks, months, years after transfusion)
    • Haemosiderosis
    • Transmission of pathogens
      • Hepatitis
      • Herpes viruses
      • HIV
      • Syphilis
      • Malaria

WBCs and transfusion reactions

WBCs in blood products can cause many complications:

  • Non-haemolytic febrile transfusion reactions
  • Transfusion-associated graft versus host disease
  • Virus transmission (CMV, EBV, …)
  • HLA alloimmunization – formation of antibodies against HLA

Methods of leucodepletion/leucoreduction (removing WBCs):

  • Buffy coat removal (removal of the layer containing WBCs and platelets after centrifugating blood) – removes only 80% of WBCs
  • Washing – removing the noncellular fluid in RBC and platelet products and replacing it with saline – removes 70 – 90% of WBCs
  • Filtration – removes 99,995% of all WBCs

Irradiation – kills all WBCs but doesn’t remove them. Useful if the function of WBCs is the problem and not the presence (i.e., antigens on them) is the problem, like in transfusion-associated graft-versus-host disease.

Acute haemolytic transfusion reaction

Etiology

  • ABO incompatibility (most common)
  • Incompatibility of other blood groups (rare)
    • Kidd incompatibility
    • Rh incompatibility
    • Kell incompatibility
    • etc.

Pathophysiology

  • Recipient antibodies binding to A or B antigens on donor RBCs -> complement activation, phagocyte activation -> haemolysis of donor RBCs
  • Activation of bradykinin (kallikrein-kinin system) -> vasodilation, hypotension, increased capillary permeability
    • Hypotension -> release of catecholamines (neuroendocrine response) -> vasoconstriction in organs rich in vascular alpha-adrenergic receptors, such as kidneys, lung, gastrointestinal tract, and skin -> tissue hypoxia, kidney damage
  • Complement activation -> cytokine release, granulocyte degranulation -> fever, hypotension, bronchospasm
  • Activation of factor XII -> DIC

Clinical features

  • Rapid onset after transfusion
  • Fever
  • Chills
  • Suffocation
  • Burning pain at IV site
  • Back pain, chest pain
  • Patients in coma or general anaesthesia
    • Bleeding in surgical area (wounds, punctures)
    • Hypotension

Complications

Treatment

  • Stop transfusion immediately if any suspicion -> confirm diagnosis with direct Coombs test and re-do compatibility testing
  • Supportive treatment
    • Fluids
    • Electrolyte correction
    • etc

Delayed haemolytic transfusion reaction

Etiology

Patients who were previously sensitized to (and therefore have antibodies against) certain RBC antigens like KIDD or D antigens. Sensitization can occur during transfusion, pregnancy or transplantation.

Pathophysiology

Antibodies bind to donor RBCs -> complement and phagocyte-mediated haemolysis.

Clinical features

  • Weeks after transfusion
  • Similar as acute haemolytic transfusion reaction but less severe
  • Can even be asymptomatic

Diagnosis

Positive direct Coombs.

Treatment

Not necessary unless there is renal impairment, just monitoring. Rarely fatal.

Non-haemolytic febrile transfusion reactions

Common complication! 0,5 – 6% of cases.

Etiology

Cytokines (pyrogens) produced by WBCs and released from RBCs during storage cause fever. Or, the recipient has antibodies against granulocytes or platelets, lysing them and releasing cytokines.

Clinical features

  • Fever
  • Flushing
  • Chills

Treatment

Stop transfusion. Give paracetamol.

Prevention

Leukoreduction.

Post-transfusion purpura

Etiology

The recipient has anti-platelet antibodies, mostly anti-HPA-1a (human platelet antigen 1a), which will destroy both recipient and donor platelets upon transfusion.

Clinical features

Treatment

Transfusion-related acute lung injury (TRALI)

Etiology

Anti-HLA or anti-HNA antibodies in donor product activates the recipient’s granulocytes.

Clinical features

  • Within 6 hours
  • Dyspnoea
  • Hypoxia
  • Cyanosis
  • Hypotension
  • Bilateral pulmonary oedema

Treatment

  • Mechanical ventilation
  • Steroids

Anaphylaxis, allergy

Etiology

  • People with IgA deficiency
  • Allergens inside transfused product (drugs etc)
  • IgE inside transfused product

Pathophysiology

People with congenital IgA deficiency can have anti-IgA antibodies. These antibodies bind to IgA in the donor plasma and initiate allergic reaction.

Clinical features

  • Allergy (mild reaction)
    • Malaise
    • Itching
    • Urticaria
    • Fever
  • Anaphylaxis
    • Laryngeal oedema
    • Anaphylactic shock

Treatment

Prophylaxis

  • IgA-free blood (washed blood) to IgA deficient patients and patients who previously had allergic reaction to transfusion

Transfusion-associated graft versus host disease (TA-GVHD)

Etiology

  • Blood transfusion from relatives
  • Severely impaired immunity

Pathophysiology

Donor lymphocytes are usually identified as foreign and destroyed by the recipient’s immune system, but when the donor and recipient HLA type is similar (relatives) the recipient’s immune system cannot recognize and destroy the donor lymphocytes. Immunodeficient persons also cannot destroy the donor lymphocytes. Donor T cells engraft in the recipient and recognize the recipient’s cells as foreign and mounts an immune response against recipient tissues.

Clinical features

  • Days or weeks after transfusion
  • Fever
  • Rash
  • Liver dysfunction
  • Pancytopaenia

Mortality > 90%

Treatment

Largely ineffective. Immunosuppressive therapy?

Prevention

Giving irradiated blood products to patients at risk for TA-GVHD.

Transfusion-related immunomodulation

Etiology

Not well known.

Clinical features

  • Transient immunosuppression occurring after allogenic blood transfusion

Prophylaxis

Leukodepletion of blood products.

Transfusion-related circulatory overload (TACO)

Etiology

Large transfusion volume, too fast infusion, cardiovascular or renal disease.

Clinical features

  • Hypervolaemia
  • Dyspnoea
  • Headache
  • Hypertension
  • Pulmonary oedema

Therapy

Stop transfusion. Upright position, diuretics, oxygen.

Prevention

Slow infusion.

Massive transfusion

Massive transfusion is the treatment of patient with severe shock. It can be lifesaving but can cause problems.

Clinical features

DIC, tissue hypoxia, bleeding.

Treatment

Fluid replacement, blood transfusion, cardiac support.

Cold blood transfusion

Etiology

Transfusion of too much unheated blood.

Clinical features

  • Decrease in tissue oxygenation
  • Bleeding
  • Arrhythmias
  • Exacerbates symptoms of hypokalaemia and hyperkalaemia

Prevention

Use of blood warmer.

Transfusion of infected blood

Etiology

Infection source

  • Poor venepuncture technique
  • Inappropriate blood storage
  • Incorrect handling

Clinical features

  • Severe shock
  • Intravascular haemolysis

Treatment

Stop transfusion. Supportive therapy for shock. IV broad spectrum antibiotics.

Haemosiderosis

Etiology

50 – 100 units of RBC transfusion.

Clinical features

Bronze skin, cirrhosis, heart failure.

Treatment

Iron chelation, phlebotomy.