Blood and Tissue Resources

Acute Hemolytic Reactions (< 24 Hours)

Clinical Presentation

Pathophysiology

Treatment/Prevention

• Fever ≥ 1°C/2°F

• Rigors

• Nausea

• Lower back pain

• Chest pain or tightness

• Acute hypotension or hypertension

• Tachycardia

• Tachypnea, wheezing, or hypoxemia

• Shock

• Wine- or cola-colored urine or jaundice

• Pain at infusion site or along infusion vein

• Urticaria, pruritis, flushing or angioedema

• Anxiety

• Unexplained bleeding from mucous membranes or infusion sites

• Hemoglobinuria

• Renal failure

• Hemoglobinemia

• Direct antiglobulin test (DAT) may be positive or negative

Incompatible blood administration results in an antigen/antibody response with activation of complement and subsequent intravascular hemolysis. Acute hemolytic reactions usually involve the ABO blood system. Misadministration of blood often results from improper identification of transfusion recipients, either at the time of phlebotomy for the type and screen specimen or at the time of transfusion. Occasionally, acute hemolysis may occur from mixing of blood with a fluid other than normal saline or from improper warming or freezing of blood.

• Maintain airway; provide oxygen and ventilatory support if necessary

• Diuretics to promote renal perfusion

• Cardiovascular support with pressor agents, as indicated (pressor agents that decrease renal blood flow are contraindicated

• Hydration to maintain urinary output

• Treatment of DIC

• Initiate transfusion reaction work-up; send unit and administration set with attached solutions to the laboratory, in addition to blood and first posttransfusion urine specimens

• Do not initiate another transfusion without Blood Bank consultation

• If patient is hemodynamically unstable, invasive monitoring of pulmonary artery occlusion pressure can guide fluid therapy

• Red cell exchange may be considered in patients with a significant load of circulating incompatible red cells

• Document reaction in patient’s chart as per institution policy

Prevention:

• ABO mistransfusions may be avoided by proper patient identification

• Administer blood only with normal saline

Sepsis/Bacterial Contamination

Clinical Presentation

Pathophysiology

Treatment/Prevention

• Fever, often > 2°C/4°F above baseline

• Chills

• Rigors

• Hypotension

• Shock

• Renal failure

• Unexplained bleeding from mucous membranes or infusion sites

Sepsis is the result of transfusion of bacterially contaminated blood components. The bacteria usually originate from the blood donor, either from venipuncture (e.g., Staphylococcus, Streptococcus) or from unsuspected bacteremia (e.g., Yersinia), but may also result from donor unit processing. Bacterial multiplication is more likely to occur in components stored at room temperature (e.g., platelets) than in components stored at refrigerator temperatures (e.g., red cells).

• Maintain airway; provide oxygen and ventilatory support if necessary

• Cardiovascular support with pressor agents, as indicated

• Hydration to maintain urinary output

• Treatment of DIC

• Initiate transfusion reaction work-up; send unit and administration set with attached solutions to the laboratory, in addition to blood and first posttransfusion urine specimens

• Do not initiate another transfusion without Blood Bank consultation

• Gram stain and culture the implicated blood component; draw blood culture from patient

• Prompt initiation of IV antibiotics if indicated by the Gram stain results

• Document reaction in patient’s chart as per institution policy

Prevention:

• Visual inspection of units for color changes, hemolysis, clots

• Blood and components should be transfused within 4 hours after issuance

• Tubing should be changed between blood units as per institutional policy

Transfusion-Related Acute Lung Injury (TRALI)

Clinical Presentation

Pathophysiology

Treatment/Prevention

• Acute respiratory distress or failure during or within 6 hours after transfusion; often dramatic onset

• Dyspnea

• Cyanosis

• Bilateral pulmonary infiltrates on chest x-ray

• Hypoxemia (O₂ sat ≤ 90% on room air or P_aO₂ ≤ 300 mm Hg)

• No evidence of circulatory overload (pulmonary artery occlusion pressure < 18 mm Hg, if available)

• Hypotension or, in some cases, hypertension

• Fever

• Tachycardia

• Transient leukopenia

• Most patients improve over 2-3 days

• Mortality rate about 10%

TRALI most commonly results from the infusion of donor antibodies directed against recipient HLA class I or II antigens or neutrophil antigens. The antigen/antibody complex activates complement with resultant neutrophil influx into the lungs. Neutrophil activation causes capillary leakage and pulmonary damage. Infrequently, recipient antibodies against cognate donor antigens may be implicated.

In a number of TRALI cases, no antibody is found. Biological response modifiers, such as membrane lipids, which accumulate during blood storage, may be implicated in these cases.

TRALI may occur with any blood product, but it occurs more commonly with products containing large volumes of donor plasma. No particular patient risk factors have been identified. Donors of implicated units are usually multiparous females who have been immunized to HLA or neutrophil antigens via pregnancy.

• Maintain airway; provide oxygen and ventilatory support if necessary

• Treat hypotension

• Diuretics and steroids are generally not helpful and may be contraindicated

• Initiate transfusion reaction work-up; send unit and administration set with attached solutions to the laboratory, in addition to blood and first posttransfusion urine specimens

• Do not initiate another transfusion without Blood Bank consultation

• Document reaction in patient’s chart as per institution policy

Additional Testing:

• Normal brain natriuretic peptide (BNP) can help distinguish from transfusion-associated circulatory overload (TACO)

• Patient serum should be tested for antibodies against HLA or neutrophil-specific antigens and the patient’s HLA type should be determined

• The blood collection facility will test involved donors for antibodies to HLA and neutrophil-specific antigens. If found, they will be compared with the patient’s phenotype

Future Transfusion:

• Implicated donors are deferred from further blood donation

• Patients are not generally at risk for recurrence

• Because HLA antibodies are more common in female donors, many centers are providing plasma from donors who are male or who have been screened.

Allergic (Severe) Anaphylactic or Anaphylactoid Reactions

Clinical Presentation

Pathophysiology

Treatment/Prevention

• Anxiety

• Wheezing, stridor, dyspnea

• Throat fullness/tightness

• Cyanosis

• Hypotension

• Tachycardia

• Urticaria

• Flushing

• Gastrointestinal distress

• Shock

• Patient is afebrile

• Loss of consciousness

• Cardiac arrest (rare)

The transfusion recipient has an antibody which may be an IgE directed against an antigen in donor plasma, such as an IgA-deficient patient who possesses antibodies to IgA. The cause, however, is often not identified.

• Maintain airway; provide oxygen and ventilatory support if necessary

• Treat hypotension - Trendelenberg position and fluids; dopamine if unresponsive

• Epinephrine if necessary

• Intubate if significant upper airway obstruction

• Initiate transfusion reaction work-up; send unit and administration set with attached solutions to the laboratory, in addition to blood and first posttransfusion urine specimens

• Do not initiate another transfusion without Blood Bank consultation

• Document reaction in patient’s chart as per institution policy

Additional Testing:

• Send a specimen for IgA level, if clinically indicated

Future Transfusion:

• Patient may be given diphenhydramine (Benadryl), steroids, and/or ephedrine prior to transfusion

• IgA-deficient patients can be given washed cellular components or components from IgA-deficient donors, although such donors are rare and components may be difficult to obtain

• Use washed or deglycerolized RBCs (or washed platelets) for patients experiencing severe reactions not caused by anti-IgA

• Consider storing autogeneic units for future transfusions

Transfusion-Associated Circulatory Overload (TACO)

Clinical Presentation

Pathophysiology

Treatment/Prevention

• Dyspnea

• Orthopnea

• Cough

• Rales on auscultation

• Cyanosis

• Headache (severe)

• Tachycardia

• Hypertension

• Congestive heart failure

• Bilateral pulmonary edema on CXR

• ↑ Pulmonary artery occlusion pressure

TACO is a life-threatening conditiondue to rapid increases in blood volume in patients with compromised cardiac or pulmonary function and/or in patients with chronic anemia and expanded plasma volumes.

It may also be caused by infusion of 25% albumin (oncotic pressure causes shift of fluid from extravascular to intravascular space).

• Upright posture

• Maintain airway; provide oxygen and ventilatory support if necessary

• Diuretics (e.g., furosemide)

• Initiate transfusion reaction work-up; send unit and administration set with attached solutions to the laboratory, in addition to blood and first posttransfusion urine specimens

• Do not initiate another transfusion without Blood Bank consultation. Circulatory overload must be addressed prior to initiation of additional blood components or volume expanders

• Phlebotomy (250 mL increments) to reduce blood volume

• Document reaction in patient’s chart as per institution policy

Additional Testing:

• ↑ brain natriuretic peptide (BNP) can help distinguish from TRALI

Future Transfusion:

• Except in conditions of ongoing rapid blood loss, blood components should be administered to at-risk patients slowly (1mL/kg/h) with attention to total fluid input and output; if extended periods of transfusion are required, request split units

• Diuretics may be given prior to or during the transfusion

Febrile Nonhemolytic Reactions

Clinical Presentation

Pathophysiology

Treatment/Prevention

• Temperature rise of > 1°C/2°F or a temperature of ≥ 38°C during or within 4 hours of transfusion, without any other obvious cause

• Chills/rigors with or without fever

• Headache

• Nausea/vomiting

• Tachycardia, palpitations, and cough may also occur

Preformed anti-HLA antibodies in the recipient (from pregnancy or previous transfusion) react with corresponding antigens on transfused white blood cells or platelets and trigger cytokine release.

Alternatively, preformed cytokines from white blood cell breakdown in the donor units may be directly infused.

Most febrile nonhemolytic reactions are benign, although some may cause significant discomfort and hemodynamic or respiratory changes.

• Non-salicylate antipyretic (acetaminophen)

• Meperidine (injection) may be useful in patients with rigors

• Initiate transfusion reaction work-up; send unit and administration set with attached solutions to the laboratory, in addition to blood and first posttransfusion urine specimens

• Do not initiate another transfusion without Blood Bank consultation

• Document reaction in patient’s chart as per institution policy

Future Transfusion:

• Leukocyte-reduced (pre-storage) blood components may be indicated in patients with a history of febrile non-hemolytic transfusion reaction or who are chronically transfused

• Platelets that are not leukocyte-reduced should be ≤ 3 days old to reduce cytokine-mediated reactions

• Plasma removal may decrease frequency of febrile reactions

• Premedication with acetaminophen has not been shown to be of benefit when leukocyte-reduced components are given