Transfusion

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.

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 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
  • Blood typing: ABO and Rh testing of recipient blood
  • RBC antibody screening: ABO, D (Rhesus factor), Duffy, Kidd
  • Compatibility testing: cross-matching of recipient plasma with potential donor RBCs to test compatibility (indirect Coombs test)

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

• Emergency transfusions
  • Transfuse packed RBCs ; with blood type O
  • If needed, fresh frozen plasma (FFP) extracted from blood type AB (Rh positive if possible)

References:^[2][3][4]

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)

• Content: red blood cells
  • Leukoreduction; : filtration of blood cells to remove leukocytes; (FDA guidelines: < 5x10⁶ leukocytes/unit) to reduce the risk of nonhemolytic febrile transfusion reactions and prevent transmission of CMV, HTLV-I/II, and EBV via leukocytes
  • Irradiation: exposure to radiation to inactivate lymphocytes; leukodepleted RBC concentrates are used in immunosuppressed patients to prevent graft-versus-host disease
• Indications
  • Generally to maintain organ perfusion and tissue oxygenation
  • Acute hemorrhage; and/or hypovolemic shock (e.g., gastrointestinal bleeding, trauma)
  • Symptomatic anemia (e.g., G6PD deficiency, aplastic anemia, β-thalassemia, sickle cell disease, anemia of chronic kidney disease)
• Situational factors must be evaluated to assess the need for transfusion.
  • Extent and cause of anemia
  • Clinical findings indicating hypoxia (tachycardia, hypotension, dyspnea)
  • Patient's ability to compensate anemia
    • Pre-existing conditions (cardiovascular, pulmonary, malignant)
    • Current condition (including prior or planned surgery)
    • Age

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

• Effect: 1 unit of packed RBCs increases Hb value approx. 1.0 g/dL
• Complications: Chronic transfusions can lead to hemochromatosis.

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

• Indications
  • Thrombocytopenia to prevent spontaneous bleeding
  • Massive blood loss
• Effect: One platelet transfusion increases the platelet count by approx. 20–40/nL.

Cryoprecipitate

• Content: clotting factors (fibrinogen, factor VIII, factor XIII), vWF, and fibronectin
• Indications: similar to FFP; preferable if large transfusion volumes are undesirable

Clotting factors

• Content: specific clotting factors that have been pooled from multiple donors
  • E.g., prothrombin complex concentrate
• 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]}

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	ABO incompatibility results in severe destruction of donor RBCs by recipient antibodies.	Rapid onset during transfusion Fever, chills, nausea, flushing Pruritus, urticaria Flank pain Dyspnea Burning pain at the IV site Patients in a coma or under general anaesthesia may present with oozing from wounds or puncture sites. Sequelae: Renal failure DIC Jaundice	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	Cessation of transfusion until an acute hemolytic transfusion reaction has been ruled out Treat with acetaminophen; recurrence uncommon
Minor allergic reactions	3% of transfusions	Recipient antibodies against plasma components in the donor blood cause an allergic reaction.	Onset during the transfusion Urticaria	Diphenhydramine
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	Soluble factors (antibodies, certain lipids) in the donor blood lead to activation of the recipient's granulocytes. Occurs particularly following transfusion of fresh frozen plasma (FFP) or platelets	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	Alloantibodies against platelets result in the destruction of platelets.	5–10 days after transfusion Mild to severe thrombocytopenia Purpura	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.	Onset: days or weeks after transfusion Fever, jaundice, anemia Dark urine	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

• Transfusion-associated circulatory overload (TACO):
  • Definition: fluid overload that can occur with transfusion of blood products . Occurs during or within 6 hours of transfusion.
  • Symptoms of hypervolemia: shortness of breath, S3 gallop, jugular venous distention, hypertension
  • Chest x-ray shows diffuse bilateral infiltrates as a sign of pulmonary edema
  • Treatment: diuretics to correct volume status, oxygen supplementation, assisted ventilation
• Hyperkalemia
• Hypocalcemia: Formation of complexes with the added citrate; occurs with whole blood transfusions, platelet transfusions, or FFP
• Hypothermia
• Sepsis if blood products are contaminated with bacteria

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