Noninfectious Complications of Blood Transfusion

Issues of Concern

Experts classify noninfectious transfusion reactions as acute or delayed based on their time of occurrence. These categories are further subclassified based on whether the reaction is immune or nonimmune mediated. For an in-depth discussion on the infectious complications related to blood transfusions, please see StatPearls' companion topic, "Infectious Complications of Blood Transfusion."

Acute Reactions

Immune-mediated reactions 

Febrile nonhemolytic transfusion reaction 

Febrile nonhemolytic transfusion reactions (FNHTRs) are one of the most commonly encountered transfusion reactions.[9] Generally associated with RBC and platelet transfusions, the symptoms are most often mild and self-limiting; however, the symptoms overlap with other serious transfusion reactions, making FNHTR a diagnosis of exclusion. Patients with FNHTR have a temperature greater than 100.4 °F (38 °C) and a change of at least 1.8 °F (1.0 °C) from their pretransfusion temperature during or within 4 hours of the transfusion. Occasionally, patients may present with no fever and only chills and rigors.[1] 

Experts believe the underlying pathophysiology is due to cytokines released by white blood cells in stored blood products that have not been leukoreduced.[10] Donor leukocytes and recipient antibodies lead to interleukin (IL)-1 release from donor leukocytes or recipient monocytes. IL-1 produces fever by stimulating prostaglandin E2 production in the hypothalamus. IL-6, IL-8, and tumor necrosis factor-α are additional implicated cytokines.

Cytokines that accumulate during storage may also play a pivotal role as the transfusion reaction risk increases with the time a unit of blood product remains stored. Clinicians should stop the transfusion immediately and administer antipyretics like acetaminophen if necessary. The patient should undergo evaluation for other causes of fever, like sepsis and an acute hemolytic transfusion reaction. Necessary lab evaluation may include blood and urine cultures and the laboratory tests discussed later in this section (Refer to "Acute hemolytic transfusion reaction" for more information on the necessary lab tests).

Meperidine can be helpful for severe rigors. Leukoreduction is a helpful technique to reduce the incidence of FNHTR.[11] Premedication with acetaminophen or an antihistamine does not help reduce the risk of FNHTR.[12] However, their benefit in patients with a previous FNHTR is unclear. 

Acute hemolytic transfusion reaction

AHTRs can occur due to immune or nonimmune-related red blood cell (RBC) hemolysis. This section will focus on immune-mediated HTR due to immunologic incompatibility between the donor and recipient RBCs. Immune-mediated-hemolysis can be due to ABO or non-ABO antibodies. These antibodies can be immunoglobulin M (IgM), which activates complement, causing intravascular hemolysis, or IgG, which mainly causes extravascular hemolysis, or both. In most cases, hemolysis due to ABO incompatibility is due to a clerical error.[13] Non-ABO hemolysis is multi-factorial. Most HTRs are due to RBC transfusion; however, less commonly, transfusion of plasma and platelet products containing high titers of isoagglutinin can also cause hemolysis of recipient RBCs.[14] 

Hemolytic transfusion reactions (HTRs) can have a broad spectrum of symptoms, including fever, chills, flank pain, and oozing from intravenous sites. Additional symptoms may be chest, back, or abdominal pain, nausea and vomiting, shock, dyspnea, hemoglobinuria, oliguria or anuria, and diffuse bleeding.[15] The severity of the reaction varies and can depend on the amount and how rapidly the incompatible blood is transfused. In severe cases, it can lead to acute kidney failure, shock, disseminated intravascular coagulation, or death. Some of these symptoms are difficult to assess in some populations, like pediatric and unconscious patients.[1]

In the presence of AHTR, the clinician should stop the transfusion immediately, and the patient should receive an intravenous infusion of normal saline to maintain a urine output of 1 mL/kg/hr and monitor renal function. Supportive measures such as supplemental oxygen may be necessary. When clinicians suspect AHTR, the following laboratory tests are necessary:

• Repeat ABO compatibility testing and crossmatch on a pre-transfusion and a post-transfusion sample.
• Perform additional antibody screenings and identification when ABO incompatibility is not the cause.
• Direct antiglobulin (DAT) or Coombs testing 
• Observe the serum and urine for pink color and analysis for free hemoglobin.
• To document hemolysis, test serum haptoglobin, lactate dehydrogenase, and unconjugated bilirubin levels.
• Check prothrombin time, activated partial thromboplastin time, fibrinogen level, and D-dimer.
• Test coagulation for disseminated intravascular coagulation if the patient has increased bleeding.
• Test serial hemoglobin level to determine the severity of hemolytic anemia and the possible need for additional RBC transfusions.

The laboratory findings associated with AHTR reveal a decreased or absent haptoglobin, elevated bilirubin, elevated lactate dehydrogenase, hemoglobinemia, or hemoglobinuria. In addition, the peripheral smear shows acanthocytes, indicating intravascular hemolysis, and spherocytes, indicating extravascular hemolysis. Clinicians can also confirm the diagnosis of immune-mediated AHTR with a positive DAT, which identifies an IgG antibody or complement coating of the RBC. The alloantibody, if present, can be confirmed in the plasma by an indirect antiglobulin test. Rarely, a DAT may be negative if antibody-coated RBCs are no longer present during the sample draw. Nonimmune causes of hemolytic transfusion reactions include improper storage of RBCs or poor thawing techniques leading to lysis, mechanical problems like small needles or malfunctioning pumps, and properties of the RBC, like donors having hemoglobinopathies.

Allergic Reactions 

Allergic reactions are another group of common complications. They can vary from mild skin manifestations such as hives, edema, pruritis, and angioedema to severe, life-threatening reactions like anaphylaxis presenting with hypotension and bronchospasm. Allergic reactions occur when a soluble antigen in the plasma of the donated blood product or the recipient reacts with preexisting IgE antibodies in the recipient or the product, causing the release of histamine from mast cells or basophils.[10]

According to the United States Centers for Disease Control and Prevention Biovigilance Network, an allergic transfusion reaction occurs when 2 or more symptoms occur within 4 hours of the completion of the transfusion. Anaphylaxis typically occurs within minutes of beginning the transfusion. The presence of hypotension or respiratory distress should alert the clinician to the possibility of anaphylaxis. Anaphylaxis is caused by a sudden massive systemic release of mediators like histamine and tryptase by mast cells and basophils, typically in response to an IgE-mediated or IgG-mediated immune reaction because the transfused substance contains a substance to which the recipient is allergic. A common example is class-specific IgG anti-IgA antibodies in patients who are IgA deficient. 

Patients experiencing an allergic transfusion reaction should have the transfusion temporarily stopped and receive 25 to 50 mg of diphenhydramine. If the hives wane and there is no evidence of dyspnea, hypotension, or anaphylaxis, the clinician can restart the transfusion. Platelet washing and storing platelets in platelet additive solution instead of plasma help reduce the incidence of allergic reactions. Products from IgA-deficient donors can help to prevent anaphylaxis in recipients with IgA antibodies. 

Transfusion-Related Acute Lung Injury  

Transfusion-related acute lung injury (TRALI) is a life-threatening complication characterized by a rapid onset of noncardiogenic pulmonary edema and lung injury within 6 hours of the transfusion. TRALI is one of the leading causes of mortality associated with blood transfusion. Experts believe a "2-hit" mechanism is responsible for TRALI. The patient's lung neutrophils are "primed" by their condition. Antihuman leukocyte antigen I and II or antihuman neutrophil antigen antibodies are soluble products like bioactive lipids acting as biologic response modifiers (BRM) in the transfused product, then activate the neutrophils.[16] TRALI due to BRMs is a nonimmune form of TRALI. The diagnosis of TRALI is one of exclusion.[17][18] Sometimes referred to as "reverse TRALI," leukocyte antibodies may be present in the recipient, often a multiparous female, that reacts with antigens on leukocytes in the transfused blood product.[17] Blood components with the highest volume of plasma have the highest incidence of TRALI. The incidence is 50 to 100 times more common in critically ill and surgical patients than in the general hospital population.[1] 

Clinically, patients present with hypoxemic respiratory insufficiency during or shortly after the transfusion of a blood product. While symptoms may present as long as 6 hours following the transfusion, they generally begin within minutes to 1 to 2 hours. The most likely symptoms are hypoxemia or a change in oxygen requirements, pulmonary infiltrates on chest imaging, pink frothy secretions from the endotracheal tube, hypotension, and cyanosis. The diagnosis is clinical, and the criteria require the presence of new acute respiratory distress syndrome during or within 6 hours after blood product administration, documented by hypoxemia and abnormal chest imaging. Clinicians document hypoxemia with an oxygen saturation of 90% or less on room air or a PaO2/FIO2 (oxygen partial pressure/fractional inspired oxygen) ratio of less than 300 mm Hg.

Clinicians must stop the transfusion immediately and administer supplemental oxygen. A trial of continuous positive or bilevel airway pressure may be helpful, but 70% to 80% of affected patients will require endotracheal intubation. In addition, hemodynamic support with fluid resuscitation or pressors may be necessary. Clinicians should use diuretics with caution, as their use may result in hypotension in patients who are hemodynamically stable. Patients who survive TRALI can receive blood transfusions in the future, but they should not receive transfusions from the same donor.

Strategies to help reduce the incidence of TRALI include the following:

• Exclude plasma donations from high-risk donors, such as multiparous women
• Screen and defer donors with HLA antibodies
• Deferral of donors implicated in a specific TRALI case 
• Selection of male donors or female donors who have never been pregnant for high plasma volume components

Nonimmune-Mediated Reactions 

Air embolism

Although rare, air can be introduced into the arterial or venous vasculature during a transfusion. Presenting symptoms for a venous air embolism can be respiratory distress, substernal chest pain, lightheadedness, or dizziness, followed by acute-onset right-sided heart failure, sudden loss of consciousness, hemodynamic collapse, or cardiac arrest. Most commonly, an arterial air embolism presents with focal neurological deficits but may also present with cardiac arrest, wheezing, and bubbles in the retinas, depending on the organ affected. Patients with an air embolism should be immediately placed in the left lateral decubitus, Trendelenburg, or left lateral decubitus head-down position for a suspected venous embolism and a supine position for an arterial embolism to force the air to move into the right ventricle with less chance of further embolization.[19] 

Transfusion-Associated circulatory overload  

TACO is a form of pulmonary edema caused by excessive fluid volume, often occurring in patients with preexisting cardiovascular or kidney disease who receive large transfusion volumes over a short duration. Symptoms include dyspnea, hypoxia, edema, hypertension, tachycardia, lung crackles, and jugular venous distension. Diagnosis begins with an oxygen saturation assessment and a chest radiograph. Management involves diuretics and ventilatory support. Differentiating TACO from TRALI can be challenging. TACO occurs with rapid transfusion, and the signs and symptoms of hypertension, heart failure, elevated central venous pressure, and increased brain natriuretic protein (BNP) or N-terminal pro-BNP (NT-pro BNP) levels support the diagnosis. In contrast, on chest imaging, TRALI presents with respiratory distress disproportionate to fluid volume, earlier onset, fever, hypotension, pink frothy secretions, hypoxemia, and bilateral infiltrates.[20][21]

Nonimmune hemolysis

Nonimmune hemolysis is a rare complication of blood product transfusion potentially caused by thermal, osmotic, or mechanical injury to RBCs; the result is hemoglobinemia and hemoglobinuria without significant clinical symptoms. 

Delayed Reactions 

As with acute reactions, clinicians divide delayed reactions into immune- and nonimmune-mediated reactions.

Immune-mediated reactions 

Delayed hemolytic transfusion reaction

A DHTR occurs more than 24 hours following a transfusion in patients who have received transfusions in the past. Most commonly, DHTRs present within 1 to 2 weeks following a transfusion, but the timing can vary between 24 hours to 28 days. Some patients may also experience a delayed serologic transfusion reaction (DSTR), an identical reaction to a DHTR, except patients are asymptomatic and have no evidence of hemolysis. DHTRs are due to undetectable antibody levels before transfusion. Exposure to RBCs containing the offending antigen provokes a response and increases antibody production. Eventually, the antibody level becomes high enough to hemolyze transfused RBCs.

The most common routes of prior exposure are pregnancy and prior blood transfusions.[22] The RBC antigens most commonly involved are those of the Kidd or Rh system.[23] According to the United States Centers for Disease Control and Prevention Biovigilance Network, to establish the diagnosis of a DHTR an affected patient must exhibit a positive direct DAT between 24 hours and 28 days after the transfusion, identification of the RBC antibody in the serum, and laboratory findings such as inappropriate hemoglobin increment, spherocytes on peripheral blood smear, or findings of hemolysis like low-grade fever, jaundice, increased LDH, increased indirect bilirubin, or decreased haptoglobin. 

Management consists of regularly monitoring the patient's hemoglobin until the hemolysis has ended and adequate hydration to avoid kidney damage. Clinicians should consider glucocorticoids, intravenous immune globulin (IVIG), or rituximab if a continued brisk fall in hemoglobin occurs. Clinicians should document the alloantibody and notify the patients to avoid future transfusions containing the antigen. 

Alloimmunization

Alloimmunization occurs when the immune system becomes sensitized to antigens not present in the host. This can lead to the production of alloantibodies against RBC-specific antigens, human leukocyte antigen (HLA) I antigens on platelets and leukocytes, HLA II antigens present on leukocytes, granulocyte-specific antigens, and platelet-specific or human platelet antigens (HPA).

The immunogenicity of these antigens, such as the Rhesus "D" blood group, determines their ability to induce antibody formation. Other important groups are Kell, Kidd, and Duffy. Alloimmunization against RBC antigens may cause acute intravascular hemolytic transfusion reactions, DHTRs, and hemolytic disease in the fetus and newborn. Alloimmunization to platelet-specific or HLA I antigens can lead to refractoriness to platelet transfusion, posttransfusion purpura, and neonatal alloimmune thrombocytopenia due to the mother's alloimmunization against fetal platelet antigens, most often resulting from previous pregnancies but can occur in a first pregnancy. 

HLA alloimmunization can occur due to exposure to platelets or white blood cells, but not RBCs, as they lack HLA antigens. HPA alloimmunization, although less common than HLA alloimmunization, can also lead to repeated suboptimal response to platelet transfusions with lower-than-expected posttransfusion count. The most relevant are HPA GPIa, GPIb, GPIIb, GPIIIA, and CD109.12.[24] Patients with Bernard-Soulier syndrome and Glanzmann thrombasthenia risk developing antibodies to GPIb/IX/V and GPIIb/IIIa platelet antigens.[25] Patients with conditions like Bernard-Soulier syndrome and Glanzmann thrombasthenia are at higher risk of developing antibodies to specific platelet antigens.

Antigen-matched transfusions would effectively prevent alloimmunization. To do so, the patient's ABO, Rh, Kell, Kidd, and Duffy systems should be typed at diagnosis or before the institution of transfusion therapy. Blood should always be matched, at least with the ABO, Rh, and Kell systems.[2] Further, leukoreduction helps prevent alloimmunization.[24] Patients who have experienced alloimmunization should receive crossmatch-compatible antigen-negative RBCs. Those who experience refractoriness to platelet transfusions should avoid future platelet transfusions as much as possible. When necessary, give ABO-compatible apheresis platelets less than 48 hours old. Consider using donor platelets from family members or select HLA-matched and crossmatched platelets. Donor platelets from family members must be irradiated to prevent graft-versus-host disease.  

Transfusion-related immunomodulation 

Transfusion-related immunomodulation (TRIM) relates to the immunosuppression effects of allogeneic blood. Pretransplant allogenic blood transfusions are known to improve survival in patients who undergo renal transplantation.[24] Research is still ongoing regarding the effects of allogenic blood product transfusion on the incidence of postoperative infection, tumor recurrence, and nosocomial infection in critically ill patients. Several studies reveal an increased risk of postoperative infection in patients who receive intraoperative transfusions.[24][25] The effects of TRIM on malignant tumor recurrence are less clear.[24][26]

Transfusion-associated graft-versus-host disease 

Transfusion-associated graft-versus-host disease is a rare complication with a high mortality rate.[27] Viable T lymphocytes present in the donor blood attack the recipient's HLA-expressing tissues, especially the skin, bone marrow, and gastrointestinal tract. Affected patients develop bone marrow aplasia and profound pancytopenia. Risk factors are immunodeficient states like hematologic malignancies, immunosuppressive medications, hematopoietic stem cell transplantation, fetuses or newborns, and when a transfusion recipient and the blood product donor share some but not all HLA antigens.

Symptoms typically develop 4 to 30 days following the transfusion and most commonly manifest as fever, rash, liver dysfunction, pancytopenia, and gastrointestinal symptoms. A skin rash is often the first presenting symptom. Hematopoietic stem cell transplantation is the only viable treatment option, but often not obtainable due to the time constraints of identifying a suitable donor. Prevention involves inactivating viable lymphocytes before transfusion.

Post-transfusion purpura 

Post-transfusion purpura (PTP) is a rare complication of platelet transfusion in individuals who develop antibodies against platelet-specific antigens once sensitized after exposure during pregnancy or a transfusion. The antigens most commonly implicated are the platelet antigens PlA1, or human platelet antigen 1a (HPA-1a) and HPA-3a. PTP leads to thrombocytopenia, petechiae, bleeding, and wet purpura, usually 5 to 10 days after the transfusion. Management includes the use of intravenous immunoglobulin and antigen-negative platelets.

Nonimmune-mediated reactions 

Iron overload

Iron overload due to transfusions occurs when patients receive recurrent transfusions for anemia, not due to iron deficiency. Some conditions that place patients at risk are thalassemia, sickle cell disease, aplastic anemia, and myelodysplastic syndrome. Generally, 15 to 20 units of RBCs will cause iron overload. Patients who undergo chronic blood transfusions require serum ferritin levels and liver and cardiac magnetic resonance imaging. 

Complications due to massive transfusion

A massive transfusion occurs when a patient receives 10 or more units of RBCs within 24 hours.[28] Common potential complications are dilutional coagulopathy, thrombocytopenia, hypocalcemia, hyperkalemia, and hypothermia.[29] Clotting factor consumption and activation due to tissue trauma or reduced clotting factor activity due to dilution, prolonged shock, hypoxia-induced acidosis, or hypothermia can all lead to coagulopathy.[29] Packed RBCs do not contain plasma and platelets, allowing them to dilute coagulation proteins and platelets. As a general rule, adults will experience a 10% decrease in the concentration of clotting proteins for each 500 mL of blood loss replaced with plasma-poor RBCs. Additionally, 10 to 12 units of transfused RBCs are associated with a 50% fall in the platelet count.[30]

Patients receive 2 to 8 units of plasma if the partial thromboplastin time or activated partial prothrombin time is more than 1.5 times normal due to dilutional coagulopathy. Clinicians administer cryoprecipitate or inactivated fibrinogen concentrate if fibrinogen levels are less than 100 mg/dL and platelets if the platelet count is less than 50,000/µL. Each unit of platelets increases the platelet count by 5,000/µL.

Sodium citrate and citric acid serve as anticoagulants for packed RBCs, and citrate binds to calcium, potentially lowering serum calcium levels. Newborns and patients who undergo a massive transfusion are at increased risk of hypocalcemia, which can manifest as hypotension, paresthesias, carpopedal spasms, tetanic contractions, and cardiac arrhythmias. To reduce the risk of hypocalcemia during transfusions, clinicians monitor the transfusion rate, blood pressure, and the corrected QT interval. Citrate metabolism occurs in the liver, and individuals with liver disease or ischemia-induced hepatic dysfunction should closely monitor their ionized calcium level.[31] Unless they are symptomatic, most patients do not require calcium replacement. When treatment is necessary, clinicians use calcium chloride or calcium gluconate.

As storage time increases, potassium leakage causes extracellular potassium levels in RBCs to rise. Transfusion-related hyperkalemia is uncommon in adults and is more likely to occur in clinical settings involving severe trauma, impaired renal function, and in newborns and infants. Hyperkalemia is common in patients who experience severe trauma due to tissue breakdown and the release of cellular potassium into the extracellular fluid. The additional potassium from blood products, low cardiac output impairing renal function, and hypocalcemia, which can intensify hyperkalemia symptoms, exacerbate this risk. Infants and newborns are particularly vulnerable due to their small blood volume and lower potassium excretion rate. Although severe hyperkalemia due to transfusion is rare in typical clinical settings, using younger and washed RBCs can help mitigate this risk.

Newborns and infants require special consideration. Mannitol and adenosine, 2 additional preservative agents, may cause osmotic diuresis and nephrotoxicity, respectively, in neonates and young infants. Fresh blood products may also be necessary. Storage of RBCs depletes levels of 2,3-diphosphoglycerate, a molecule in RBCs that helps release oxygen. In infants, the percentage of fetal hemoglobin and the concentration of 2,3-diphosphoglycerate determine the efficiency of oxygen delivery to tissues. The newborn body has not yet developed the ability to replenish 2,3-diphosphoglycerate.

Hypotensive reaction

Hypotension can occur as an underlying part of a transfusion reaction or a patient's condition. Clinicians consider a standalone hypotensive reaction if a drop in the systolic BP of 30 mm Hg or more occurs and the systolic blood pressure is 80 mm Hg or less or a 25% drop in the baseline systolic BP of children happens. Hypotensive reactions are likely due to a release of bradykinin and particularly affect patients on angiotensin-converting enzyme inhibitors or those exposed to filtered blood.[32]

Clinical Significance

In the United States, the risk of adverse events related to blood product transfusion is approximately 0.2%, with more than 80% being allergic or hypotensive reactions or FNHTRs.[9] The Serious Hazards of Transfusion (SHOT) haemovigilance scheme in the United Kingdom (UK) provides comprehensive data on transfusion-related adverse events.[26] Transfusion delays and TACO are the most common causes of transfusion-related deaths reported to SHOT, accounting for 21 of 35 deaths reported. The risk of death related to transfusion in the UK is 1 in 63,537, and the risk of serious harm is 1 in 15,450 per issued blood component.[26]

Each complication of blood product transfusions necessitates specific preventive measures and careful monitoring to minimize adverse outcomes and enhance patient safety. With any transfusion reaction, the transfusion should be immediately discontinued. Various modifications are available to clinicians to help mitigate potential transfusion complications.

Modifications and Specialized Blood Products

• Leukoreduction: This removes white blood cells from blood products, reducing the risk of FNHTRs and HLA alloimmunization. 
• Irradiation: Blood products are irradiated to prevent TAGVHD in susceptible individuals, such as those undergoing bone marrow transplants or with compromised immune systems.
• Whole blood: This replaces lost blood volume quickly instead of administering plasma, packed RBCs, and platelets separately.
• Frozen RBCs: This is reserved for patients with rare blood types, ensuring the availability of compatible units.
• Washed RBCs: These remove the small amount of residual plasma in the unit, eliminating plasma proteins and other potential allergens.
• Volume-reduced RBCs: Clinicians centrifuge the blood product immediately before the transfusion to remove the storage solution for patients at risk of transfusional volume overload.

Specific Complications and Their Clinical Significance

Although RBCs are the most common blood component transfused, platelets account for the most reported reactions. Platelet transfusions are associated with a high frequency of febrile and anaphylactoid reactions. Clinicians must rapidly differentiate between life-threatening and non life-threatening cases when evaluating transfusion reactions. Potentially fatal TACO, TRALI, AHTRs, anaphylaxis, and hyperhemolysis syndrome require immediate medical intervention.

Febrile nonhemolytic transfusion reactions

FNHTRs are one of the most common transfusion reactions and occur in approximately 1% of all transfusions.[14] Clinicians diagnose FNHTR after excluding other causes of fever like sepsis and other transfusion reactions. FHNTRs are benign and cause no longterm harm. Treatment is symptomatic with antipyretics and meperidine for rigors when necessary. Leukoreduction helps prevent future FNHTRs.[27]

Transfusion-related acute lung injury

Though the incidence of TRALI has significantly decreased with the implementation of TRALI mitigation strategies like the avoidance of plasma donation from multiparous female donors, TRALI remains a serious and potentially fatal transfusion-related complication. Clinicians must consider TRALI in any patient who develops acute hypoxemia, usually within 6 hours of beginning a transfusion. Mortality rates for TRALI vary based on the patient population studied and range from 5% to 17% per some study results to as high as 41% to 67% in critically ill individuals.[28]

Transfusion-associated circulatory overload

TACO is the leading cause of transfusion-related mortality in the United States, occurring in approximately 1% of all individuals undergoing a transfusion.[29] Clinicians should consider TACO in patients with respiratory distress or hypertension within 12 hours of receiving a transfusion, with even higher suspicion for those with preexisting heart or kidney disease. 

Allergic reactions and anaphylaxis

Allergic reactions to blood products manifesting as itching and hives occur in approximately 1% to 3% of patients undergoing platelet and plasma transfusions and 0.1% to 0.3% of patients undergoing RBC transfusions. Clinicians can establish the diagnosis of an allergic reaction if the symptoms remain limited to itching, hives, localized edema, or rash without progression to systemic symptoms after stopping the transfusion and administering diphenhydramine. If clinicians establish the diagnosis of an allergic reaction, the patient can receive the remaining blood product. Platelet washing and transfusing platelets stored in platelet additive solution instead of plasma can help alleviate future allergic reactions.[30]

Anaphylaxis occurs in 1 in 20,000 to 1 in 50,000 units of transfused RBCs and is a potentially fatal reaction.[14] Patients who experience anaphylaxis should avoid plasma products in the future if possible. When necessary, solvent or detergent-treated plasma or washing RBC and platelet products can help prevent future reactions. Patients with immunoglobulin A (IgA) deficiency with anti-IgA antibodies should receive blood products from IgA-deficient donors. 

Acute hemolytic transfusion reaction

AHTRs occur at a rate of 2.0 per 100,000 RBC transfusion, with the most common cause being clerical errors leading to ABO-incompatible transfusions.[1][14][1] AHTRs can lead to acute kidney injury (AKI), DIC, and hemodynamic collapse. Establishing strict transfusion protocols, including a stringent patient identification process, can mitigate the incidence of these reactions. 

Hyperkalemia

A concern in massive transfusions, patients with impaired renal function, and infants, hyperkalemia due to transfusion is likely transient, and the true incidence of complications like arrhythmia and cardiac arrest is unclear. A rapid infusion rate increases the risk, especially through a central venous catheter. Using fresher or washed RBCs and monitoring serum potassium levels can mitigate this risk.

Iron overload

Iron overload due to chronic blood transfusions can lead to liver diseases, including cirrhosis and hepatocellular carcinoma, cardiomyopathy, and endocrine disorders such as diabetes and hypothyroidism. Cardiomyopathy due to iron overload is a common cause of mortality in patients who are transfusion-dependent, making routine surveillance imperative. 

Delayed hemolytic transfusion reactions

A severe form of DHTR is hyperhemolysis seen in patients with sickle cell disease. Patients who experience hyperhemolysis experience destruction of not only the transfused RBCs but also their own RBCs, partially due to the "bystander" effect due to complement activation. Affected patients will have hemoglobin lower than their pretransfusion hemoglobin.[31] A hyperhemolytic crisis is potentially fatal if not treated rapidly. Clinicians use glucocorticoids, additional blood products, and IVIG. Rituximab, eculizumab, and tocilizumab are potential options as well. Erythropoietin administration helps reduce the need for additional transfusions. 

Enhancing Healthcare Team Outcomes

Noninfectious complications of blood transfusions range from mild to life-threatening and require prompt recognition and management. Symptoms such as fever, chills, pruritus, and urticaria are common and often resolve without intervention. However, more severe reactions, including respiratory distress, hemoglobinuria, hypotension, jaundice, and abnormal bleeding, can indicate a potentially fatal response. Identifying these complications may be particularly challenging in patients with complex clinical conditions or those under general anesthesia. Healthcare team members must remain vigilant, assess patients immediately, and contact transfusion services when reactions are suspected. Early recognition and intervention are crucial to improving patient safety and transfusion outcomes.

Effective management of noninfectious complications of blood transfusions requires a collaborative, interprofessional approach to ensure patient safety and optimal outcomes. Advanced clinicians are crucial in identifying at-risk patients, ordering appropriate transfusions, and promptly recognizing adverse reactions. Nurses are essential in closely monitoring patients during and after transfusions, documenting any signs of complications, and communicating concerns with the healthcare team. Pharmacists contribute by reviewing transfusion-related medications, identifying potential interactions, and ensuring appropriate blood product selection.

Laboratory professionals provide critical support in verifying blood compatibility and conducting diagnostic tests to confirm suspected transfusion reactions. Strong interprofessional communication and coordinated care strategies, including strict patient and blood product identification protocols, rapid response systems, and continuous education, enhance team performance and patient-centered care. Healthcare teams can effectively mitigate risks, improve transfusion safety, and optimize patient outcomes by fostering a culture of collaboration and vigilance.