Complications of Transfusion Reaction

Acute transfusion reactions present as adverse signs or symptoms during or within

24 hours of a blood transfusion. The most frequent reactions are fever, chills, pruritus, or
urticaria, which typically resolve promptly without specific treatment or complications. Other
signs occurring in temporal relationship with a blood transfusion, such as severe shortness of
breath, red urine high fever, or loss of consciousness may be the first indication of a more
severe potentially fatal reaction.

Early Complications:
• Hemolytic reactions (immediate and delayed)
• Non-hemolytic febrile reactions
• Allergic reactions to proteins, IgA
• Transfusion-related acute lung injury
• Reactions secondary to bacterial contamination
• Circulatory overload
• Air embolism
• Thrombophlebitis
• Hyperkalemia Citrate toxicity Hypothermia
• Clotting abnormalities (after massive transfusions)

Late complications:
• Transmission of infection
• Viral (hepatitis A, B, C, HIV, CMV) Bacterial (Salmonella)
• Parasites (malaria, toxoplasma) Graft-vs-host disease
• Iron overload (after chronic transfusions) Immune sensitization (Rhesus D antigen)
 1-Acute hemolytic transfusion reactions
Acute hemolytic transfusion reactions occur when ABO-incompatible blood is
transfused, resulting in recipient antibodies attaching to donor RBC antigens and forming an
antigen-antibody complex. This antigen-antibody complex activates complement, resulting
in intravascular RBC lysis with release of RBC stroma and free Hb. Immune system activation
also results in bradykinin release (leading to hypotension) and mast cell activation (causing
serotonin and histamine release). The net result may be shock, renal failure due to Hb
precipitation in renal tubules, and DIC. Many signs and symptoms of an acute hemolytic
transfusion reaction appear immediately and include fever, chest pain, anxiety, back pain,
and dyspnea. Many are masked by general anesthesia, but clues to the diagnosis include
fever, hypotension, hemoglobinuria, unexplained bleeding, or failure of Hct to increase after
transfusion.

2- Delayed hemolytic transfusion reactions

Delayed hemolytic transfusion reactions occur because of incompatibility of minor
antigens and are characterized by extravascular hemolysis. They present 2 days to months
after transfusion. Patients complain of no or minimal symptoms but may display signs of
anemia and jaundice. Lab studies reveal a positive direct antiglobulin test,
hyperbilirubinemia, decreased haptoglobin levels, and hemosiderin in the urine.

3- Febrile nonhemolytic transfusion reactions

Febrile nonhemolytic transfusion reactions are the most common transfusion
reactions, occurring in approximately 1% of RBC transfusions and up to 30% of platelet
transfusions. They occur when anti-leukocyte antibodies in a recipient react with white blood
cells in a transfused blood product. Signs and symptoms include fever, chills, tachycardia,
discomfort, nausea, and vomiting.

4- Allergic transfusion reactions

Allergic transfusion reactions are common, occurring in 1% to 3% of transfusions.
They arise from recipient antibody response to donor plasma proteins. Urticaria with pruritus
and erythema is the most common. Allergic transfusion reactions are common, occurring in
1% to 3% of transfusions. They arise from recipient antibody response to donor plasma
proteins.
5- Transfusion-Related Acute Lung Injury (TRALI)

Transfusion-Related Acute Lung Injury (TRALI) is a condition of severe

pulmonary insufficiency following blood, FFP, cryoprecipitate, or platelet transfusion. Signs
and symptoms include fever, dyspnea, hypoxemia, hypotension, and pulmonary edema
developing within 4 hours of transfusion. TRALI happens when anti-HLA antibodies and anti-
leukocyte antibodies present in donor plasma cause the recipient leukocytes to injure their
own tissues. Most cases are tracked to female donors who have previously been pregnant
and developed anti-HLA antibodies.

6- TACO (transfusion-associated circulatory overload)

TACO (transfusion-associated circulatory overload) is a condition of
circulatory congestion secondary to the fluid volumes administered as transfusions. The
symptoms are similar to congestive heart failure and include dyspnea, pulmonary edema,
tachycardia, and increased jugular venous distention. While TRALI also produces
pulmonary edema, signs of circulatory overload are seen in TACO that helps differentiate
the two. TACO often affects patients at risk for congestive heart failure and occurs in less
than 1% of transfusions.

7- Graft-Versus-Host Disease (GVHD)

Graft-Versus-Host Disease (GVHD) is a rare and almost always fatal
complication of blood transfusions resulting from an attack of immunocompetent donor
lymphocytes on the host’s various tissues. After the majority of transfusions, the donor
lymphocytes are destroyed by the recipient’s immune system, preventing GVHD. However, if
the host is immunodeficient or if there is a specific type of partial HLA matching between the
donor and recipient, GVHD is more likely to occur. It can develop 4 to 30 days after
transfusion, with patients typically presenting with fever and erythematous
maculopapular rash that may become generalized. Other symptoms include anorexia,
vomiting, abdominal pain, and cough.

8- Coagulopathy
A massive transfusion of RBCs may lead to a dilutional coagulopathy, as
plasma-reduced RBCs contain neither coagulation factors nor platelets. Secondly,
hemorrhage, as a consequence of delayed or inadequate perfusion, can result in DIC. This
causes consumption of platelets and coagulation factors and may account for the numerical
distortion of clotting studies appearing out of proportion to the volume of blood transfused.

9- Hypothermia
Red blood cells are stored at 4 degrees Celsius. Rapid transfusion at this
temperature will quickly lower the recipient’s core temperature and further impair
hemostasis. Hypothermia reduces the metabolism of citrate and lactate and increases the
likelihood of hypocalcemia, metabolic acidosis and cardiac arrhythmias. A decrease in core
temperature shifts the oxyhemoglobin dissociation curve to the left, reducing tissue oxygen
delivery at a time when it should be optimized.

10- Bacterial and viral infections

Bacterial and viral contamination of blood components is an infrequent
complication of transfusion. However, if it does occur, the potential for fulminant sepsis in a
recipient is associated with high mortality. It can result from contamination during
venipuncture or if a symptomatic donor is bacteremic or viremic at the time of donation.
Symptoms occur during or shortly after transfusion of the contaminated unit and include
high fever, rigors, erythema and cardiovascular collapse.

11- Air Embolism

The incidence of air embolism has now reduced markedly with the use of
plastic blood bags. Nevertheless, air can enter a central catheter while blood administration
sets or blood bags are being changed or if blood in an open system is infused under pressure.

12- Transfusion Associated Immunomodulation (TRIM)

The down-regulation of recipient’s cellular immune response caused by transfusion of
allogeneic blood has traditionally been defined as transfusion associated
immunomodulation (TRIM). The detrimental clinical impacts of TRIM are increased chances
of post- operative infections and cancer recurrence and possibly a transfusion-related multiple
organ dysfunction syndrome.