Transfusion reaction

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]; Associate Editor(s)-in-Chief: Khuram Nouman, M.D. [2] Amandeep Singh M.D.[3]

Overview

Blood products, when transfused even after cross matching, elicit some reactions. The transfusion reactions are classified into anaphylactic reaction, bacterial infection, acute hemolytic reaction, febrile non-hemolytic reaction, transfusion-related acute lung injuryTRALI, transfusion-associated circulatory overload, transfusion-associated microchimerism (TA-MC), iron overload, and transfusion-associated Graft-versus-Host Disease (GvHD). The symptoms may range from fever to life threatening anaphylaxis. The treatment of each different type of transfusion reaction is different.

Types of Transfusion Reactions

Anaphylactic Reaction

• An anaphylactic (or severe allergic) reaction can occur at a rate of 1 per 30,000-50,000 transfusions.
• These reactions are most common in people with selective IgA deficiency (although IgA deficiency is often asymptomatic, and people may not know they have it until an anaphylactic reaction occurs).

Bacterial Infection

• Blood products can provide an excellent medium for bacterial growth, and can become contaminated after collection while they are being stored.
• The risk is highest with platelet transfusion, since platelets must be stored near room temperature and cannot be refrigerated.
• The risk of severe bacterial infection and sepsis is estimated (as of 2001) at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions.

Acute Hemolytic Reaction

• This is a medical emergency resulting from rapid destruction (hemolysis) of the donor red blood cells by host antibodies.
• The most common cause is clerical error (i.e. the wrong unit of blood being given to the wrong patient).
• The symptoms are fever and chills, sometimes with back pain and pink or red urine (hemoglobinuria).
• The major complication is that hemoglobin released by the destruction of red blood cells can cause acute renal failure.

Febrile Non-hemolytic Transfusion Reaction

• This is the most common adverse reaction to a blood transfusion.
• Symptoms include fever and dyspnea 1 to 6 hours after receiving the transfusion.
• Such reactions are clinically benign, causing no lasting side effects or problems, but are unpleasant via a blood transfusion is estimated, as of 2006, at 1 per 2 million units transfused. Bacterial infection is a much more common problem.

Transfusion-Related Acute Lung Injury (TRALI)

• TRALI is a syndrome of acute respiratory distress, often associated with fever, non-cardiogenic pulmonary edema, and hypotension.
• It may occur as often as 1 in 2000 transfusions.
• Symptoms can range from mild to life-threatening, but most patients recover fully within 96 hours, and the mortality rate from this condition is less than 10%.

Transfusion-associated Microchimerism (TA-MC)

• Transfusion-associated microchimerism is the stable persistence of donor's genetically distinct cells (usually <5%) in a recipient's circulation following fresh blood transfusion, especially in the setting of trauma.
• As a result of the current advancement in polymerase chain reaction techniques, TA-MC has been demonstrated among patients with trauma following blood transfusion, pregnancy and organ or stem cell transplantation. Several studies have implicated other forms of microchimerism, including fetomaternal microchimerism, with acute and chronic illnesses such as congenital heart block in a patient with neonatal lupus erythematosus and systemic sclerosis.
• Genetic factors such as the TNF (-308A) single nucleotide polymorphisms (SNP) have been implicated in the development of TA-MC. The risk of developing TA-MC is largely dependent on the clinical setting, i.e., it is rare in situations which do not involve massive trauma. Although leukoreduction removes > 99.9% of donor's white blood cells, it has not been proven to prevent the development of TA-MC.

Transfusion-associated Graft-vs-Host Disease (GvHD)

• GVHD refers to an immune attack by transfused cells against the recipient. This is a common complication of stem cell transplantation, but an exceedingly rare complication of blood transfusion.
• It occurs only in severely immunosuppressed patients, primarily those with congenital immune deficiencies or hematologic malignancies who are receiving intensive chemotherapy.
• When GVHD occurs in association with blood transfusion, it is almost uniformly fatal. Transfusion-associated GVHD can be prevented by irradiating the blood products prior to transfusion.

Volume Overload

• Patients with impaired cardiac function (e.g. congestive heart failure) can become volume-overloaded as a result of blood transfusion, leading to edema, dyspnea (shortness of breath), and orthopnea (shortness of breath while lying flat).
• This is sometimes called TACO, or Transfusion Associated Circulatory Overload.

Iron Overload

• Each transfused unit of red blood cells contains approximately 250 mg of elemental iron.
• Since elimination pathways for iron are limited, a person receiving numerous red blood cell transfusions can develop iron overload, which can in turn damage the liver, heart, kidneys, and pancreas. The threshold at which iron overload becomes significant is somewhat unclear, but is likely around 12-20 units of red blood cells transfused.

Following table summarizes the difference between transfusion-related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO):

Parameters	Transfusion-related acute lung injury (TRALI)	Transfusion-associated circulatory overload (TACO)
Fever	±	−
Blood pressure	Hypotension	Hypertension
Respiratory distress	+	+
JVP	Non-distended	Distended
Respiratory auscultation	Rales	Rales + S3 heart sounds may be present
CXR	Bilateral pulmonary infiltrates	Bilateral pulmonary infiltrates
Fluid balance	Neutral	Positive
Diuretics	Responsive only when there is fluid overload	Improvement with diuretics
Ejection fraction	Normal	Decreased
BNP	<250 pg/mL	>1200 pg/mL
PCWP	<18 mm Hg	>18 mm Hg
WBC	Unchanged	Transient decreased

Treatment of Transfusion Reactions

• The most important step in treating a presumed transfusion reaction is to stop the transfusion immediately (saving the remaining blood and IV tubing for testing) and to provide supportive care to the patient.
• More specific treatments depend on the nature and presumed cause of the transfusion reaction.
• Most hospitals and medical centers have transfusion reaction protocols, which specify testing of the blood product and patient for hemolysis, bacterial contamination, etc.

The following table shows different types of transfusion reactions along with their treatment:

Transfusion Reaction	Time of onset	Fever	Rigors	Rash	Blood Pressure	Additional Features	Labs	Treatment	Prevention	Mechanism/ Examples
Anaphylactic reaction	Rapid onset	−	−	−	Hypotension	Wheezing Stridor Cyanosis Soft tissue edema	CBC ABG Type and screen	Stop the transfusion immediately S/C epinephrine IV epinephrine(in case of severe hypotension)	Avoid clerical errors Proper storage record Repeat type and screen before transfusion Proper blood storage conditions	IgA deficiency
Bacterial Infection	Rapid onset	++	+	±	Hypotension is common Occasionally hypertension	Fever > 2 Tachycardia	CBC Urine complete examination Blood and urine culture Transfusion set culture Clotting profile	Stop the transfusion Check identity on blood unit Look for clerical errors Supportive management(O2 inhalation,normal saline) Broad spectrum antibiotics for bacterial infections Inform blood bank	Extensive screening of blood Decrease storage time Leukodepletion Bactericidal treatment	±
Acute hemolytic reaction	Rapid onet	+	+	±	Hypotension	Chest pain Apprehension Flank pain Dark urine(Hemoglobinura) Renal failure Oozing from venipuncture site ( DIC)	CBC Urine complete examination ABO compatibility Serum haptoglobin Serum LDL Serum bilirubin Prothrombin time Coomb's test=+ve	Stop the transfusion immediately Look for clerical errors Alert blood bank Maintain IV access Supportive management To prevent renal failure-give low dose dopamine,normal saline,mannitol for diuresis Treat DIC(if happens)	Avoid clerical errors Proper storage record Repeat type and screen before transfusion Proper blood storage conditions	ABO incompatibility
Transfusion Reaction	Time of onset	Fever	Rigors	Rash	Blood Pressure	Additional Features	Labs	Treatment	Prevention	Mechanism/ Examples
Febrile non-hemolytic transfusion reaction	1/2 to 1 hour	+, with chills	+	−	No Effect	Can occur in first few hours Fever rise of 1-2	No labs usually required	Slow or Stop the transfusion Give Acetaminophen for fever	Leukoreduction	Cytokine in storage
Transfusion-related acute lung injury (TRALI)	within 6 hours	±	±	−	Hypotension	Cough Pink frothy sputum Respiratory distress Pulmonary edema	ABGs CBC SpO2 monitoring CXR-pulmonary infiltrates HLA typing(remove donor from the list)	Stop the transfusion immediately O2 inhalation Ventilatory support Supportive treatment Diuretics for volume overload Inform the blood bank Consult hematologist	Donor whose blood cause TRALI must be put on non-donor list	Donor anti-leukocyte antibodies
Transfusion-associated circulatory overload (TACO)	usually over hours	−	−	−	Hypertension	Dyspnea Orthopnea Cough Headache Tachycardia Decrease spO2 Increase JVP Increase CVP	SpO2 monitoring CXR Serum BNP ABGs	Stop transfusion Supportive therapy O2 supplementation Ventilatory support Diuretics Exchange transfusion(if transfusion is unavoidable) Controlled phelbotomy	Slow rate of transfusion Avoid unnecessary transfusion Cardiac evaluation	+++