A healthcare worker holds a blood bag ready for transfusion.
Transfusion is a life-saving procedure that is used in trauma and during surgery, as well as in conditions such as anaemia and other haemotological diseases. It is relatively safe in that a rigid screening and cross-matching procedure is required before a transfusion is administered, adverse events still occur in some of the patients who require transfusions.
Worldwide clinical data have shown that 0.5% to 3% of patients who receive transfusions experience some degree of transfusion reaction. Fortunately, most transfusion reactions are mild in nature but can, in rare instances, be more serious or even fatal. The key to ensuring that patients do not develop more serious transfusion reactions is early recognition and the administration of prompt management strategies, along with preventative measures to minimize the risk of such events.
This guide sets out to cover the different types of transfusion reactions, the etiology and clinical manifestations, as well as preventative measures, with an evidence-based approach.
A transfusion reaction can be defined as an unwanted response of the recipient's immune system or physiology to transfused blood or blood components. Transfusion reactions may be:
They may occur due to:
Transfusion reactions can be divided into acute (immediate) and delayed reactions based on the time of occurrence and the mechanism.
Acute transfusion reactions are the immediate, most common, potentially dangerous, and most preventable type, and therefore immediate recognition and management are crucial.
Acute hemolytic transfusion reaction is a potentially life-threatening complication that often arises due to clerical error in ABO matching at the time of administration of the blood. The estimated incidence is 1: 25,000 transfusion.
The reaction occurs as a result of massive hemolysis of the transfused red blood cells, resulting in acute kidney injury, hemoglobinuria, hypotension, shivering, back and flank pain, etc. Untreated AHTR can be fatal ( up to 10%), hence the need for strict transfusion protocols is paramount.
This is the most frequently encountered adverse reaction to blood transfusion. They arise due to the liberation of cytokines from the donor white cells or by antibodies in the recipient reacting against recipient cells.
The incidence is estimated to be between 0.1%-1% and is more common in platelet transfusion. The symptoms typically include a rapid rise in body temperature (at least 1 °C) along with chills and rigors. This reaction is not life-threatening, though very distressing to the patient, and it is imperative to exclude more serious causes of fever during transfusion.
A woman touches her shoulder, which shows signs of irritation.
Allergic transfusion reactions are fairly common (incidence 1%-3%) and arise due to hypersensitivity to plasma proteins found in donor blood. The reactions vary from localized symptoms like urticaria and itching to more generalized skin rashes, but may also include bronchospasm.
These usually resolve quickly on administration of antihistamines and transfusion can be continued unless the symptoms are severe and can be continued unless more significant symptoms develop.
Anaphylactic transfusion reactions are a rare but potentially life-threatening complication of blood transfusion. The incidence is around 1: 20,000 to 1: 50,000 transfusions and is more common in patients with IgA deficiency who have developed IgA antibodies that react with the IgA in donor plasma. The onset can be extremely rapid with respiratory and circulatory collapse. The transfusion needs to be stopped immediately.
TRALI is another severe complication that is caused by transfusion, which causes non-cardiogenic pulmonary edema as a result of antibody-mediated activation of leukocytes, and results in sudden and severe respiratory distress. It is one of the major causes of transfusion-related mortality in the world, with an estimated incidence of about 1: 5000 transfusions, and symptoms can occur within 6 hours of transfusion.
TACO arises when the circulatory volume exceeds the recipient's physiological capacity, particularly when giving blood to patients with underlying heart or renal disease or infants. The estimated incidence is between 1%-8%, and symptoms include shortness of breath, coughing, hypertension, tachypnea, and Pulmonary edema.
These reactions appear days or weeks after the transfusion and are often underdiagnosed because they may be subtle or delayed in presentation.
Delayed hemolytic transfusion reactions arise because of a secondary antibody response to red blood cell antigens; they generally appear 3-14 days after the transfusion. Previously sensitized antibodies were present but could not be detected by cross-matching.
Clinical manifestations include fever, jaundice, and a mild drop in hemoglobin levels. Although they are typically less serious than acute hemolytic transfusion reactions, they are not without consequence to the recipient's recovery.
These infections are caused by pathogens present in the donated blood; the incidence of transfusion-transmitted infections has dramatically reduced with the advent of sophisticated screening tests for infected blood.
The current estimate of transfusion-transmitted Hepatitis B is about 1 in 200,000, of transfusion-transmitted Hepatitis C is about 1 in 2 million, and of transfusion-transmitted HIV is about 1 in 1.5 to 2 million transfusions. Despite the excellent donor screening and nucleic acid testing (NAT) now performed, the risk of transfusion-transmitted infections is not zero.
Patients receiving chronic transfusion therapy, such as those with thalassemia, are prone to developing iron overload over a prolonged period as iron is deposited in the heart, liver, endocrine organs, and bone.
TA-GVHD is a rare but usually fatal reaction that occurs because of the transfusion of lymphocytes that cause engraftment within the host tissue. Over 90% of affected patients die as a result of their illness, with symptoms including fever, skin rash, liver disease, bone marrow aplasia, and multisystem failure. Irradiation of blood products prevents the onset of TA-GVHD, particularly in immunocompromised individuals.
Conditions that put a patient at higher risk:
There are a variety of preventative measures that are critical in reducing the risk of transfusion reactions and improving the overall safety of blood transfusions.
A healthcare professional is holding a test tube of blood while typing on a keyboard.
Correct blood typing and cross-matching between donor and recipient ensures that a blood product will not be immunologically incompatible, which helps prevent reactions such as acute hemolytic transfusion reactions caused by ABO mismatch.
Double-checking before and during transfusion of blood product and the patient's labels and documentation are important for the prevention of clerical errors. Misidentification accounts for some severe transfusion reactions, so strict patient identification protocols should be utilized to increase patient safety.
Leukoreduction, the removal of white blood cells from blood components before transfusion, reduces the buildup of inflammatory cytokines and the incidence of febrile nonhemolytic transfusion reactions by about 50 to 70% and is of particular importance to patients undergoing multiple transfusions.
Irradiation inactivates donor lymphocytes, preventing attacking recipient tissues; for immunocompromised patients, irradiation is critical in preventing transfusion-associated graft versus host disease, a rare and potentially lethal complication of transfusion.
Blood products administered slowly and vital signs carefully monitored during infusion allow detection of potential warning signs. This is especially critical in high-risk populations and is important in preventing TACO.
Patients with prior mild transfusion reactions can benefit from the administration of antihistamines or antipyretics to help reduce the chance of repeated mild reactions. Though not routine in all patients, it can improve the tolerability for selected populations.
Newer screening techniques, such as nucleic acid testing (NAT), can be used to detect viruses more quickly in donated products, greatly reducing the risk of transfusion-transmitted infections to extremely low levels and enhancing the safety of blood transfusion.
Early signs during transfusion that we will need to monitor include:
Intervention: Stop the transfusion and begin investigations.
While transfusion reactions are infrequent in clinical practice, they are an important aspect of patient safety. The majority are manageable and minor in nature, but there are severe possibilities such as TRALI, AHTR, and anaphylaxis, which are time-critical.
Since the improvement in screening processes, compatibility testing, and the implementation of strict transfusion monitoring procedures, the safety and effectiveness of blood transfusions have become greatly enhanced. We need to be vigilant when administering transfusions and follow clinical protocols strictly. Early recognition, timely management, and prevention have to be implemented to achieve a positive outcome for the patients.
World Health Organization (WHO) - Blood Safety and Availability:
https://www.who.int/news-room/fact-sheets/detail/blood-safety-and-availability
AABB (American Association of Blood Banks) Guidelines:
https://www.aabb.org
National Institutes of Health (NIH) - Transfusion Reactions:
https://www.ncbi.nlm.nih.gov/books/NBK482202/
Centers for Disease Control and Prevention (CDC) - Blood Safety:
https://www.cdc.gov/bloodsafety
StatPearls - Transfusion Reactions Clinical Review:
https://www.ncbi.nlm.nih.gov/books/NBK482202/
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