A blood transfusion is a common medical procedure where a patient receives donated blood or specific components, such as red blood cells, plasma, or platelets, through an intravenous line. This intervention is often necessary to replace blood lost during surgery or trauma, or to treat conditions like anemia. While transfusions are life-saving and generally safe, the body can sometimes perceive the donated product as foreign, triggering an adverse transfusion reaction. Although serious reactions are rare, recognizing these responses is crucial for safe patient care.
Classification of Transfusion Reactions
Medical professionals categorize adverse transfusion events primarily in two ways: by the time they occur and by the underlying mechanism. Reactions are first divided into acute, which manifest during the transfusion or within 24 hours, and delayed, which appear more than 24 hours afterward, sometimes weeks later. This timing distinction helps narrow the list of potential causes.
The second classification separates events into immunologic and non-immunologic categories. Immunologic reactions involve the patient’s immune system directly, such as antibodies attacking donor cells or proteins. Non-immunologic reactions are caused by physical or chemical factors, such as volume overload, bacterial contamination, or the physical breakdown of blood cells before infusion.
The Five Major Acute Transfusion Reactions
Acute Hemolytic Transfusion Reaction (AHTR)
Acute Hemolytic Transfusion Reaction (AHTR) is an immune-mediated event typically caused by the accidental transfusion of ABO-incompatible red blood cells. This incompatibility causes the recipient’s pre-existing antibodies to rapidly attack and destroy the donor red cells while they are still in circulation. Symptoms often begin within minutes of starting the transfusion and can include fever, chills, back or flank pain, and a sense of doom. Hemoglobin released from the destroyed cells is filtered by the kidneys, sometimes leading to red or dark urine and potential kidney failure.
Febrile Non-Hemolytic Transfusion Reaction (FNHTR)
The Febrile Non-Hemolytic Transfusion Reaction (FNHTR) is one of the most common reactions, characterized by a rise in the patient’s temperature, often accompanied by chills or rigors. This non-hemolytic event is primarily caused by the recipient’s immune system reacting to cytokines accumulated in the blood product during storage. The reaction is usually not severe and is diagnosed only after more serious causes of fever, such as AHTR or bacterial contamination, have been ruled out. Pre-treatment of blood products to remove white blood cells (leukoreduction) has significantly reduced the incidence of this type of reaction.
Allergic Reaction
Transfusion-related allergic reactions occur when the patient reacts to plasma proteins or other soluble substances present in the donor blood product. The severity can vary widely, ranging from mild urticaria to severe anaphylaxis. Mild cases present with localized signs like hives, itching, or flushing, often responding quickly to antihistamines. Severe anaphylactic reactions involve widespread symptoms such as bronchospasm, respiratory distress, and hypotension, requiring immediate emergency treatment.
Transfusion-Related Acute Lung Injury (TRALI)
Transfusion-Related Acute Lung Injury (TRALI) typically develops within six hours of the transfusion and is considered a leading cause of transfusion-related mortality. TRALI is characterized by acute respiratory distress, presenting as sudden severe shortness of breath and hypoxemia. The underlying cause is the infiltration of the lungs with fluid, known as non-cardiogenic pulmonary edema, which is often triggered by donor antibodies reacting with the recipient’s white blood cells.
Transfusion-Associated Circulatory Overload (TACO)
Transfusion-Associated Circulatory Overload (TACO) is a non-immunologic reaction resulting from the infusion of blood product volume that the patient’s circulatory system cannot accommodate. This condition leads to fluid overload, which stresses the heart and causes pulmonary edema due to increased hydrostatic pressure. Symptoms usually develop during or shortly after the transfusion and include sudden difficulty breathing, elevated blood pressure, and signs of heart failure like an engorged jugular vein. Patients with pre-existing heart or kidney conditions are at the highest risk for developing TACO.
Delayed Reactions and Other Adverse Events
Reactions that occur after the 24-hour acute window are termed delayed reactions and can pose a diagnostic challenge because of their later onset. One of the most common delayed events is the Delayed Hemolytic Transfusion Reaction (DHTR), which typically appears between three and ten days following the transfusion. DHTR occurs when the recipient’s immune system, having been exposed to a foreign red cell antigen in the past, rapidly produces a new antibody response that destroys the transfused red cells. This destruction causes a gradual drop in the patient’s hemoglobin levels, sometimes presenting with unexplained fever, jaundice, or new anemia.
Another rare delayed event is Transfusion-Associated Graft-versus-Host Disease (TA-GVHD), which occurs when donor lymphocytes engraft and attack the recipient’s tissues, particularly in immunocompromised patients. This reaction can manifest days to weeks later with symptoms affecting the skin, liver, and bone marrow.
Immediate Steps Following a Reaction
When any adverse event is suspected during a transfusion, the first action is to stop the infusion immediately. The intravenous line should be kept open by flushing it with a saline solution to maintain access for potential emergency medication. The patient’s medical provider and the hospital blood bank must be notified at once so that an investigation can begin. Initial patient management focuses on assessing and stabilizing the patient’s airway, breathing, and circulation. Blood samples and the remaining blood product are sent back to the laboratory for urgent testing to identify the exact cause of the reaction.