• Clinical science

Transfusion

Abstract

Transfusion of whole blood and fractionated blood components is a widespread method for managing numerous conditions. Packed RBCs are the most commonly transfused products and are primarily used for the treatment of acute or chronic blood loss. The rationale behind RBC transfusion is not simply to improve the Hb level, but rather to maintain organ perfusion and tissue oxygenation. The decision to transfuse RBCs therefore depends on the Hb level, the patient's hemodynamic status, and comorbidities (e.g., cardiovascular disease). Fresh frozen plasma (FFP) and cryoprecipitate, platelet transfusions, and clotting factor transfusions are also available.

Pretransfusion testing must be performed to prevent the transfusion of incompatible RBCs and subsequent immune hemolytic reactions. The testing involves blood typing of the recipient blood (ABO and Rhesus group), antibody screening of the recipient blood, and compatibility testing (crossmatching recipient plasma and donor RBCs). The most common transfusion reactions are minor allergic reactions (urticaria) and nonhemolytic febrile reactions. However, some transfusion reactions, such as the acute hemolytic transfusion reaction, may be life-threatening and require immediate supportive care. If transfusion reactions do occur, immediate cessation of the transfusion is essential.

Blood group systems

ABO blood type system and Rhesus blood group system

Incidence
ABO antigen on RBCs Antibodies in plasma Packed RBC compatibility
Blood type O ∼ 45% No antigens A and B antibodies O
Blood type A ∼ 40% A antigen B antibodies A, O
Blood type B ∼10% B antigen A antibodies B,O
Blood type AB ∼ 5% A and B antigens No A or B antibodies AB, A, B, O
Rhesus negative ∼ 15% - Rhesus (Rh) antibodies after previous sensitization Rh negative
Rhesus positive ∼ 85% - No Rh antibodies Rh positive, Rh negative

Individuals with blood type O negative are “universal donors” of packed RBCs! Individuals with blood type AB positive are “universal recipients” for packed RBCs!

References:[1]

Pretransfusion testing

Pretransfusion testing must be performed to prevent the transfusion of incompatible blood products and subsequent immune hemolytic transfusion reactions.

  • Recipient's plasma sample
    • Usually EDTA tube
    • Obtained within 3 days prior to testing in hospital inpatients, or patients with a history of transfusion or a history of pregnancy in the previous 3 months, or uncertain history of either
    • Proper identification of the patient and labeling of the sample is vital.
      • The person drawing the blood must identify the patient.
      • The sample must be labeled properly and match the information of the requisition for the blood bank.
      • Most blood banks require two separate samples to avoid possible mistakes.
  • Procedure

Compatibility testing must be performed before an RBC unit can be released from the blood bank for transfusion!

References:[2][3][4]

Transfusion Products

Whole blood transfusions

  • Content: donor blood or recipient (autologous) blood
  • Indications
    • Rarely used except for massive transfusions for significant blood loss
    • Elective autologous blood transfusion for elective surgery

Fractionated blood components

Packed red blood cells (RBC)

The indication for transfusion is not solely dependent on the Hb value, but rather on a combination of clinical findings and pre-existing conditions!

  • Transfusion thresholds
Transfusion recommendation (American Association of Blood Banks)
Clinical situation Hb threshold Transfusion
  • Hospitalized patients (independent of clinical findings)
≤ 6 g/dL
  • Recommended
  • Hospitalized patients (hemodynamically stable)
    • Postoperative patients
    • ICU patients
    • Cardiovascular disease
    • Symptomatic anemia
< 7–8 g/dL
  • Recommended
  • Maintain Hb > 7–9 g/dL

Jehovah's Witnesses who do not want to accept blood transfusions should be asked to provide documentary evidence (e.g., advance directive card refusing blood). However, in life-threatening situations in which the patient cannot be consulted, or there is uncertainty concerning the documentation, it is advisable not to withhold blood!

Fresh frozen plasma (FFP)

  • Content: plasma; all cellular components have been removed from the transfusion product
  • Indications
    • Warfarin overdose
    • Clotting factor deficiency (e.g., liver cirrhosis; , DIC)
    • Substitution of plasma (in the case of massive transfusions)
  • ABO compatibility must be considered.
    • According to current guidelines, the Rhesus factor does not have to be considered.
  • Lowering the risk of transmitting infections
    • Inactivation of viruses
    • Quarantine: FFPs are cooled (-30°C) to minimize the risk of HIV and HCV transmission and only released if the donor repeatedly tests negative for HIV and HCV after a quarantine period of 4 months.
AB0 Rhesus compatible FFP
A Rh+ or Rh- A or AB
B Rh+ or Rh- B or AB
0 Rh+ or Rh- 0,A,B or AB
AB Rh+ or Rh- AB

For fresh frozen plasma transfusions (which contain the donor antibodies), individuals with blood type O are universal recipients and individuals with blood type AB are universal donors!

Platelet transfusion

Cryoprecipitate

Clotting factors

  • Content: specific clotting factors that have been pooled from multiple donors
  • Indications: specific clotting factor deficiencies, life-threatening bleeds, warfarin overdose

Antithrombin III (AT III)

  • Indication:
    • In hereditary AT III deficiency to optimize thrombosis prophylaxis with heparin
    • In DIC if applicable
  • Effect: increases the effects of heparin
  • Inhibitor of coagulation, which is synthesized in the liver → inhibition of thrombin, Xa, IXa, XIa, and XIIa

References:[5][6][7][8][9][10][11][12][4]

Transfusion reactions

Clerical errors are the most common cause of transfusion reactions!

Immunologic reactions

Frequency Pathomechanism Clinical features Treatment
Acute hemolytic transfusion reaction
  • 1 in 250,000 transfusions
  • Rapid onset during transfusion
  • Immediate cessation of transfusion
  • Confirm diagnosis
    • Test patient's blood: direct Coombs test , plasma free hemoglobin > 25 mg/dL
    • Repeat typing and cross-matching of the transfusion product to identify and record causative blood products
    • Immediate communication with the blood bank is vital to identify and potentially prevent further clerical errors.
  • Supportive care
    • Immediate infusion of saline to aid diuresis and manage hypotension
    • Vasopressors may be required to maintain perfusion.
    • Cardiac monitoring and hemodialysis if hyperkalemia secondary to severe hemolysis occurs
    • Coagulation studies; administer FFP and platelets if DIC develops (see “Treatment” of DIC)
Nonhemolytic febrile transfusion reaction
  • 3% of transfusions
  • After periods of long storage of blood products, cytokines may leak from donor RBCs and subsequently cause a mild immunologic reaction in the recipient.
  • In addition, preformed recipient antibodies lead to lysis of the few remaining leukocytes within donor RBC concentrates, resulting in an inflammatory reaction.
  • Onset during or within 1–6 hours after transfusion
  • Clinical features: fever, chills, malaise
Minor allergic reactions
  • 3% of transfusions
Anaphylaxis
  • 1 in 50,000 transfusions
  • Anti-IgA IgG in recipients with IgA deficiency bind to IgA on the surface of donor RBCs and trigger mast cell degranulation.
  • Sudden onset during the transfusion
  • Shock, hypotension
  • Epinephrine, hemodynamic stabilization, and airway management
Transfusion-related acute lung injury (TRALI)
  • < 0.08% of transfusions
  • Onset: during or within 6 hours of transfusion
  • Sudden onset
  • Symptoms and imaging results are generally the same as in ARDS: dyspnea, hypotonia, fever; chest x-ray showing diffuse infiltrates; in some cases, leukopenia
  • Hypotension (due to hypovolemia)
  • Discontinue transfusion; contact blood bank
  • Supportive management:
    • Maintain sufficient ventilation/oxygen supply
    • Control hemodynamic parameters
    • Anti-inflammatory therapy with IV steroids (only in specific circumstances)
  • Mortality rate generally below 20%
Post-transfusion purpura
  • Rare
  • Occurs primarily in women who have a history of multiple pregnancies
  • IVIG therapy or plasmapheresis
Delayed hemolytic transfusion reaction
  • Rare
  • Occurs in patients who were previously sensitized to specific RBC antigens during transfusions, pregnancy, or transplantations
  • Re-exposure to the antigens results in a rapid increase in antibodies that bind to donor RBCs and cause extravascular hemolysis.
  • No acute therapy required
  • Antibody testing to prevent future reactions

If fever develops in a patient receiving a transfusion, repeat donor and patient blood typing and crossmatching to rule out an incompatibility reaction!

Nonimmunologic reactions

References:[6][13][14][15][16][17][18][19][4][20]