Blood Transfusion

Indications

Guidelines on red blood cell transfusion from the American Association of Blood Banks recommend a restrictive approach for patients with nonhemorrhagic anemia.[8] Although definitions may vary, anemia is typically defined as a hemoglobin level less than 13 g/dL in men and 12 g/dL in women. Current practice uses a more restrictive threshold to guide transfusion decisions; previously, a liberal strategy, typically using a cutoff of hemoglobin less than 10 g/dL, was used; however, hemoglobin target values have significantly changed over the years.[9]

Current guidelines for red blood cell transfusion generally use a restrictive threshold. Although there is some variation in threshold values, 7.0 g/dL is generally agreed upon for asymptomatic healthy patients. Results from multiple studies showed that this is an acceptable threshold in other patient populations, including those with gastrointestinal tract bleeding and critically ill patients. The guidelines recommend thresholds of 7.5 g/dL and 8 g/dL for patients with coronary artery disease and those undergoing orthopedic surgical procedures, respectively.[10] However, this may be due to a lack of literature on the use of a 7 g/dL threshold in studies evaluating these patient populations. The guidelines and clinical trials on Transfusion Requirements in Critical Care also recommend a threshold of 7 g/dL for critically ill patients.[10][11][12][13]

Transfusion Limits in Acute Myocardial Infarction

The landmark Myocardial Ischemia and Transfusion trial studied the effects of liberal versus conservative transfusion standards in patients with acute myocardial infarction. In the restrictive strategy group, hemoglobin was maintained between 7.0 and 8.0 g/dL, while in the liberal transfusion group, transfusion was initiated if hemoglobin was less than 10.0 g/dL. The liberal strategy group received a mean of 2.5 units of packed red blood cells, compared with 0.7 units in the restrictive group. Results from this study showed a trend toward increased 30-day mortality and recurrent myocardial infarction with lower transfusion limits, although this did not reach statistical significance. When stratified by 4 goal hemoglobin levels (greater than 7.0, 8.0, 9.0, and 10.0 g/dL), lower hemoglobin levels were associated with increased mortality and cardiac events.[9][14][15]

These findings contrast with results from the Restrictive and Liberal Transfusion Strategies in Patients With Acute Myocardial Infarction trial, which showed noninferiority when transfusion was initiated at a hemoglobin level less than 8.0 g/dL compared with initiation at a hemoglobin level less than 10.0 g/dL in patients with acute myocardial infarction. Results from this study showed that the lower transfusion threshold was noninferior to the higher transfusion threshold at 30 days; however, the major adverse cardiac event rate was overall higher with the lower transfusion threshold. At a 1-year follow-up, patients in the restrictive transfusion group had significantly higher major adverse cardiac event rates and mortality. This trial also had lower power, with approximately 630 participants compared with approximately 3500 participants in the Myocardial Ischemia and Transfusion trial.[9][16][17]

In patients who are actively bleeding after traumatic injury, results from one study of adult patients with severe trauma at risk for major bleeding showed that a restrictive transfusion strategy, with a target hemoglobin level of 7.0 to 9.0 g/dL, was not inferior to a more liberal approach of transfusing to a goal of 10 to 12 g/dL.[18] Transfusion may also be indicated in patients with active or acute bleeding, and in those with symptoms related to anemia (for example, tachycardia, weakness, and dyspnea on exertion) and hemoglobin levels less than 8 g/dL.[19] In such cases, anemia is defined as a decreased circulating red cell mass, measured as grams of hemoglobin per 100 mL of whole blood. Anemia may result from external loss, inadequate production, internal destruction, or a combination of these factors. Although many patients experiencing active bleeding become anemic, anemia alone is not an indication for transfusion. Severe hemorrhage can cause shock, which reflects an insufficient supply of oxygen to support cellular metabolism. Red cell mass repletion is one facet of the treatment of hemorrhagic shock.

Unless the patient is actively bleeding, clinicians should transfuse 1 unit of packed red blood cells at a time, which typically increases hemoglobin by 1 g/dL and hematocrit by 3%. Clinicians should then check the posttransfusion hemoglobin level.[20] However, in cases of major bleeding, a massive transfusion protocol may be necessary, with blood components administered in a balanced ratio of 1:1:1 or 2:1:1 for packed red cells, plasma, and platelets.[21] The American Society of Anesthesiologists advises transfusion at hemoglobin levels of 6 g/dL or less. However, results from more recent studies showed decreased mortality with preanesthetic hemoglobin levels greater than 8 g/dL, especially in patients undergoing renal transplant.[22]

Patients can be transfused with whole blood or component therapy (ie, red blood cells, plasma, and platelets). For most of the 1900s, whole blood was used for transfusions; however, advances in technology made component therapy more common. Results from studies evaluating whole-blood therapy compared with component therapy, especially in trauma, using low-titer type O whole blood, showed that whole-blood transfusion may reduce hemorrhage-related mortality in the prehospital setting, although whole blood has a shorter shelf life than red blood cell component therapy.[23]

The transfusion of fresh frozen plasma is common, but specific indications for its use are limited. Evidence is insufficient for its use in many clinical scenarios, such as prophylaxis in patients who are not bleeding.[24][25][26] Fresh-frozen plasma transfusion is sometimes indicated for bleeding patients to replace lost coagulation factors. Clinical situations that meet this criterion include cardiopulmonary bypass, massive transfusion, decompensated liver disease, extracorporeal pulmonary support techniques, and acute disseminated intravascular coagulation. In the past, fresh frozen plasma, combined with vitamin K, was indicated for warfarin excess in cases of life-threatening hemorrhage. Fresh-frozen plasma is rarely needed for vitamin K deficiency or warfarin reversal because prothrombin complex concentrate is widely available. The exception is concomitant plasma volume deficit.[27]

Platelet transfusion is beneficial in cases of platelet deficiency or dysfunction. In patients with bone marrow failure, prophylactic platelet transfusion is indicated when there are no additional bleeding risk factors and platelet counts are below 10 × 10⁹/L. If other associated risk factors are present, the transfusion threshold may be raised to 20 ×10⁹/L. Platelet counts greater than 50 ×10⁹/L are required before invasive procedures. In active hemorrhage, platelet transfusion should be performed when thrombocytopenia contributes to the hemorrhage and the platelet count is less than 50 × 10⁹/L. When diffuse microvascular bleeding is present, platelet count should be maintained above 100 ×10⁹/L.[28][29]

Cryoprecipitate transfusion is indicated in dysfibrinogenemia or fibrinogen deficiency in the setting of bleeding, injury, invasive procedures, or acute disseminated intravascular coagulation. Cell salvage technology is available and is used to recover blood during surgical procedures for reinfusion to the patient. This technology can reduce the risks associated with allogeneic (donated) blood. Results from a Cochrane review found that in certain surgical procedures, cell salvage reduced blood loss volume and the need for allogeneic transfusions, without significant changes in adverse events.[30]

Contraindications

No absolute contraindications exist, but some patients or their parents (in pediatric cases) may refuse transfusions for religious reasons.[31] 

Equipment

Blood products are transfused through intravenous tubing with filters. The filters, which typically have pore diameters of 170 to 260 µm, are also used to prevent particulate debris from being administered. However, particulate entrapment promotes bacterial growth, and the American Association of Blood Banks advises against using a filter for more than 4 hours. Before transfusion, the tubing should be primed with an isotonic, calcium-free, blood-compatible solution, such as normal saline. Citrate is used as a preservative in packed red blood cells, and clots will form in the intravenous line if the calcium level exceeds the amount that citrate can buffer.[32] The equipment required for a blood transfusion includes the following:

1. Blood components or whole blood can be provided through various central venous access devices or peripheral intravenous catheters. The following sizes should be considered:
   • 20- to 22-gauge for routine transfusion in adults
   • 16- to 18-gauge for rapid transfusion in adults
   • 22- to 25-gauge for pediatrics
2. Blood filters
3. The administration of platelet-poor plasma requires supplies that often differ by product and brand.
4. Infusion devices, such as infusion pumps, blood warmers, rapid infusers, and pressure devices, can be used to transfuse blood components.
5. A pressure infusion device may be needed for the rapid transfusion of blood components.
6. A blood warmer device is often needed to prevent hypothermia in the rapid administration of cold blood components, for instance, in trauma settings or operating rooms.

Personnel

Two qualified healthcare professionals should verify blood products before administration, and patients should be monitored during transfusion by qualified personnel. Blood transfusions can be performed by various healthcare professionals, such as registered nurses, licensed vocational nurses, or licensed practical nurses. Nurses usually perform this task under the direction of a clinician. Regarding blood transfusion training requirements, most professionals, such as registered nurses and licensed vocational nurses, learn how to administer blood transfusions through medical training and educational programs.

Preparation

Preparation for blood transfusion involves pretransfusion compatibility testing between the recipient's antibodies and the donor's red blood cells. Pretransfusion testing involves obtaining a sample of the recipient’s blood for a type and screen. The type and screen test verifies the recipient’s blood type and determines whether the recipient has any unexpected non-ABO antibodies that might cause a reaction. Multiple methods are available for performing this screen. If the screen results are negative, a reaction is very unlikely. Blood should be obtained rapidly for the patient when required. If the screen results are positive, many blood banks will crossmatch and hold 2 units of blood for the patient in case transfusion is needed. Another prerequisite for blood transfusion is obtaining the patient's consent, if possible.[33]

The following list includes important steps to follow before proceeding with a blood transfusion:

Find Current Type and Crossmatch

• Obtain a blood sample, which lasts up to 72 hours
• Send the sample to the blood bank
• Ensure that the blood sample has the correct labeling with the date and time
• Wait for the blood bank to crossmatch and prepare the needed units

Obtain Informed Consent and Health History

• Discuss the procedure with the patient
• Confirm the past medical history and any allergies
• The supervising clinician should have obtained signed consent from the patient [33]

Obtain Large-Bore Intravenous Access

• Obtain 18-gauge or larger intravenous access
• Each unit should be transfused within 2 to 4 hours
• A second intravenous access site should be secured in case the patient needs additional intravenous medications
• Normal saline is the only fluid that can be administered with blood products

Assemble Supplies

• Y tubing with an inline filter
• 0.9% sodium chloride solution
• Blood warmer

Obtain Baseline Vital Signs

• Baseline vital signs include heart rate, temperature, blood pressure, pulse oximetry, and respiratory rate
• Respiratory sounds and urine output should also be documented
• The clinician should be notified if the temperature is greater than 100 °F

Obtain Blood from the Blood Bank

• Once the blood bank confirms that the blood is ready, ensure delivery from the blood bank 
• Packed red blood cells can only be given one unit at a time
• Once the blood has been released for the patient, the transfusion should begin within 20 to 30 min and be completed within 4 hours. 

Technique or Treatment

Here are some of the general steps healthcare professionals should follow when performing a blood transfusion:

1. Verify the blood product.
2. Explain the features of a transfusion reaction to the patient. The patient should inform the nursing staff of any signs or symptoms that occur during the transfusion.
3. Obtain and document baseline vital signs, lung sounds, urine output, and skin color.
4. Prepare the Y tube with 0.9% sodium chloride and have the blood unit ready on an infusion pump.
5. The blood should infuse slowly for the first 15 min, for instance, 2 mL/min or 120 mL/h.
6. Staff should supervise the patient for the first 15 min because most transfusion reactions occur during this period.
7. The transfusion rate can be increased after this period if the patient is stable and shows no signs of a transfusion reaction.
8. Document vital signs after 15 minutes, then every 1 hour, and finally at the end of the transfusion.
9. During the transfusion, assess for any signs of transfusion reactions.If a reaction is suspected, stop the transfusion immediately.
10. Disconnect the blood tubing from the patient.Inform the clinician, stay with the patient, and assess the patient’s status.
11. After the transfusion, flush the Y tubing with normal saline and dispose of the used Y tubing in the biohazard bin.
12. Obtain posttransfusion vital signs.
13. After the procedure, some patients may experience soreness at the puncture site, but this should resolve quickly.

Complications

Blood transfusions have multiple complications, including infections, hemolytic reactions, allergic reactions, transfusion-related lung injury, transfusion-associated circulatory overload, and electrolyte imbalance (see Image. Transfusion Reaction Signs and Symptoms).[34][35][36] According to the American Association of Blood Banks, febrile reactions are the most common, followed by transfusion-associated circulatory overload, allergic reaction, transfusion-related lung injury, hepatitis C viral infection, hepatitis B viral infection, HIV infection, and fatal hemolysis, which is extremely rare and occurs in approximately 1 in 2 million transfused units of red blood cells. For comparison, the lifetime odds of dying from a lightning strike are about 1 in 161,000. A list of approximate risks per unit of red blood cell transfusion, adapted from the American Association of Blood Banks clinical guidelines published in October 2023, is provided below.[37]

Adverse Event and Approximate Risk per Unit Transfusion of Red Blood Cells

• Febrile reaction: 1:161
• Allergic reaction: 1:345
• Transfusion-associated circulatory overload: 1:125
• Transfusion-related lung injury: 1:1250
• Anaphylactic reaction: 1:5000
• Hepatitis B infection: 1: 1,100,000
• Hepatitis C infection: 1:1,200,000
• HIV infection: 1:1,600,000

Febrile Reactions

Transfusing with leukocyte-reduced blood products, as most blood products in the US are, may help reduce febrile reactions. If a febrile reaction occurs, the transfusion should be halted and the patient evaluated, as a hemolytic reaction can initially appear similar; clinicians should consider performing a hemolytic or infectious workup. Treatment includes acetaminophen and, if needed, diphenhydramine for symptomatic control. After treatment and exclusion of other causes, the transfusion can be resumed at a slower rate.[38]

Transfusion-Associated Circulatory Overload

Transfusion-associated circulatory overload is characterized by respiratory distress secondary to cardiogenic pulmonary edema. This reaction is most common in patients already in a fluid-overloaded state, such as patients with congestive heart failure or acute renal failure. Diagnosis is based on symptom onset within 6 to 12 hours of transfusion, clinical evidence of fluid overload, pulmonary edema, elevated brain natriuretic peptide levels, and a response to diuretics.[39] Preventive efforts and treatment include limiting transfusions to the minimum necessary, transfusing over the slowest possible time, and administering diuretics before or between transfusions.

Allergic Reaction

Allergic reactions often manifest as urticaria and pruritus and occur in less than 1% of transfusions. More severe symptoms, such as bronchospasm, wheezing, and anaphylaxis, are rare. Allergic reactions may occur in patients who are IgA-deficient because exposure to IgA in donor products can cause severe anaphylactoid reactions. Washing the plasma from the cells before transfusion can help prevent this reaction. Mild symptoms, such as pruritus and urticaria, can be treated with antihistamines. More severe symptoms can be treated with bronchodilators, corticosteroids, and epinephrine.[40]

Transfusion-Related Lung Injury

Transfusion-related lung injury is uncommon, occurring in about 1:12,000 transfusions. Patients develop symptoms within 2 to 4 hours after receiving a transfusion. Patients develop acute hypoxemic respiratory distress, similar to acute respiratory distress syndrome. Patients have pulmonary edema and normal central venous pressure without evidence of left heart failure. Diagnosis is made based on a history of recent transfusion, chest radiography findings showing diffuse patchy infiltrates, and the exclusion of other etiologies. Although transfusion-related lung injury has a 10% mortality rate, the remaining 90% of cases resolve within 96 hours with supportive care only.[41]

Infections

Infections are potential complications. However, the risk of infection has decreased due to screening of potential donors, so the risks of hepatitis C and human immunodeficiency virus infection are less than 1 in 1 million.[42] Bacterial infection can also occur, but it occurs rarely, at about 1 in every 250,000 units of transfused red blood cells.

Fatal Hemolysis

Fatal hemolysis is extremely rare, occurring only in 1 in nearly 2 million transfusions. Fatal hemolysis results from ABO incompatibility, and the recipient’s antibodies recognize and induce hemolysis in the donor’s transfused cells. Patients develop an acute onset of fevers and chills, low back pain, flushing, dyspnea, tachycardia, and shock. Treatment is to stop the transfusion, leave the intravenous access in place, administer normal saline intravenously, and maintain urine output greater than 100 mL/h; diuretics may also be needed. Cardiorespiratory support may be provided as appropriate. A hemolytic workup should also be performed, including sending the donor blood and tubing, as well as posttransfusion laboratory samples from the recipient, to the blood bank:

• Retype and crossmatch 
• Direct and indirect Coombs tests
• Complete blood count, creatinine, prothrombin time, and partial thromboplastin time (draw from the other arm)
• Peripheral smear
• Haptoglobin, indirect bilirubin, lactate dehydrogenase, plasma-free hemoglobin
• Urinalysis for hemoglobin

Electrolyte Abnormalities

Electrolyte abnormalities can also occur, although they are rare and more likely associated with large-volume transfusion. Hypocalcemia can result because citrate, an anticoagulant in blood products, binds with calcium.[43] Hyperkalemia can occur from the release of potassium from cells during storage. Risk is higher in neonates and patients with renal insufficiency.[44] Hypokalemia can result from alkalinization of the blood because citrate is converted to bicarbonate by the liver in patients with normal hepatic function.

Clinical Significance

As mentioned in the introduction, the science of transfusion medicine, including red blood cell transfusion, has evolved significantly over the past century. The field of transfusion medicine has evolved and now encompasses multiple medical specialties. The ability to transfuse red blood cells into patients safely and rapidly has revolutionized the care of trauma patients, patients undergoing surgical procedures, and patients with gastrointestinal bleeding, among other conditions. Transfusion medicine will continue to evolve, and ongoing research will improve this process and evaluate alternative methods for delivering oxygen to cells. These advances could potentially reduce the risk of reactions and infection and improve storage.

Enhancing Healthcare Team Outcomes

Our understanding of blood transfusion has improved dramatically over the past 3 decades. Unlike before, empiric blood transfusions are no longer the norm. Although blood products provide clinical benefit, they can also cause harm. Healthcare professionals who treat patients needing a blood transfusion should consult a hematologist if uncertainty about the indications remains. Interprofessional team collaboration is crucial for treating patients undergoing blood transfusions and those having adverse reactions to transfusions. The key is to reduce harm associated with unnecessary blood transfusions.

Effective transfusion practice requires a coordinated interprofessional approach that emphasizes appropriate patient selection, safe administration, rapid recognition of adverse reactions, and clear communication across the care team. Physicians and advanced practitioners are responsible for assessing the indication for transfusion, obtaining informed consent when possible, selecting the appropriate blood product, and reassessing the patient’s response. Nurses play a central role in verifying patient and product identities, monitoring vital signs, educating patients about the symptoms of transfusion reactions, and promptly stopping the transfusion if a reaction is suspected. Pharmacists may assist with medication review, anticoagulation reversal strategies, blood conservation efforts, and evaluation of therapies that may reduce transfusion needs. Laboratory and blood bank professionals support patient safety through compatibility testing, product preparation, and communication of urgent findings. Ethical care requires respect for patient autonomy, including religious objections to transfusion, while ensuring that patients receive clear information about risks, benefits, and alternatives. Consistent documentation, closed-loop communication, and timely escalation of concerns enhance patient-centered outcomes, reduce preventable complications, and improve team performance.