Blood Transfusion Reaction

Blood transfusion reactions are adverse responses to the infusion of any blood component, including red cells, white cells, platelets, plasma, cryoprecipitate, or other factors. They may be classified as acute (within 24 hours of administration) or delayed (occurring days, weeks, months, or even years later). They range from mild urticarial reactions that may be treated easily to fatal hemolytic reactions. It is important to note that almost all fatal hemolytic reactions are attributable to human error. Blood transfusion reactions can be mediated by the immune system or by nonimmune factors (Table 1).

Table 1 Classification of Transfusion Reactions by Type

TYPE AND TIMING	CAUSE	SIGNS AND SYMPTOMS
Allergic; usually occurs within 4 hr	Sensitivity to foreign proteins; immunoglobulin E (IgE)–mediated type 1 hypersensitivity reaction	Mild: Hives, urticaria, fever, flushing, itching	Febrile nonhemolytic transfusion reaction; most common transfusion-related adverse event; occurs within 4 hr of transfusion
Sensitization to donor white blood cell antigens; transfusion of proinflammatory cytokines due to blood component storage	Fever, chills, headache, flushing, muscle aches, respiratory distress, cardiac dysrhythmias	Acute hemolytic transfusion reaction; variable timing	ABO incompatibility reaction to red blood cell antigens; interaction between antigens on donor and/or recipient erythrocytes
Fever, chills, dyspnea, hemoglobinuria, low back pain, flushing, tachycardia, hypotension, vascular collapse, shock, cardiac arrest	Anaphylactic; reactions usually begin within a few seconds or minutes of transfusion	Administration of donor's immunoglobulin A (IgA) proteins to recipient with anti-IgA antibodies; recipient is often IgA deficient	Restlessness, urticaria, wheezing, stridor, angioedema, bronchoconstriction, shock, cardiac arrest
Transfusion-transmitted infections; variable timing	Bacterial or viral infections (West Nile, HIV, cytomegalovirus, viral hepatitis), protozoal infection (malaria), prion disease	Patient develops the symptoms of the disorder; high fever, shock, tachycardia	Transfusion-associated circulatory overload; usually within first 2–6 hr
Infusion of blood at a rapid rate that leads to fluid volume excess and hydrostatic pulmonary edema	Pulmonary congestion, restlessness, cough, shortness of breath, orthopnea, hypoxemia, hypertension, distended neck veins	Transfusion-related lung injury; occurs within 6 hr of transfusion	Antibodies to human leukocytes or neutrophils are present in transfusion components; neutrophils become localized in lung tissue
Hypoxemia, bilateral pulmonary infiltrates, dyspnea, cyanosis, hypotension	Delayed serologic/delayed hemolytic transfusion reactions (DSTR/DHTR); occur 48 hr or more after transfusion	Delayed serologic/hemolytic reactions, post-transfusion purpura, transfusion-related immunomodulation, graft versus host disease	Varies with condition

The immune system recognizes red blood cells, platelets, white blood cells, or immunoglobulins as “non-self” because the donor's blood carries foreign proteins that are incompatible with the recipient's antibodies. Typing, screening, and matching of blood units before administration eliminate most incompatibilities, but all potential incompatibilities cannot be screened out in the matching process. Adverse reactions to transfused blood products in hospital transfusion services are estimated at 282 per 100,000 units transfused. Most deaths are related not to allergic reactions but to circulatory overload or transfusion-related lung injury.

Nonimmune factors are usually related to improper storage. Complications to transfusion reactions include acute bronchospasm, respiratory failure, acute tubular necrosis, and acute renal failure. The most severe reactions can cause anaphylactic shock, vascular collapse, or disseminated intravascular coagulation. Also, current research shows that patients who receive transfusions have an increased risk of infection because the transfusion depresses the immune system for weeks and even months afterward.

Causes ⬆ ⬇

The recipient's immune system responds to some transfusions by directing an immune response to the proteins in the donor's blood. Nonimmune factors are involved when the blood or components are handled, stored, or administered improperly. The hemolytic reaction occurs when the donor's blood does not have ABO compatibility with the recipient's blood. Accidental transfusion of red blood cells usually happens either because of misidentification of the patient or blood component or because of confusing two patients with the same or similar names.

Individuals at greatest risk for transfusion reactions are those who receive massive blood transfusions. The transfusions may be administered over a short period of time, such as with trauma victims with severe blood loss or recipients of liver transplants. Individuals who receive a great number of transfusions throughout a more extended period of time, such as people with leukemia or sickle cell disease, are also at greater risk. Over time, they develop more and more protective antibodies after each unit of blood is received. Eventually, they carry so many antibodies in their systems that they react much more readily than a person who is transfusion-naive.

Genetic Considerations ⬆ ⬇

Blood types are heritable and correspond to antigens present on red blood cells. A person with blood type A must have inherited one or two copies of the A allele. The resulting genotype would be either AA or AO, expressing the A antigen as well as B antibodies. Someone who is blood type B inherited one or two copies of the B allele and could have a genotype of either BB or BO. A person with blood type AB must have both the A and the B alleles, resulting in the AB genotype; the genotype of a person who is type O must be OO. Each parent donates one of their two ABO alleles to each child. The Rh factor allele is inherited independently. An Rh-positive person has one or two Rh-positive alleles with a genotype of Rh+/Rh+ or Rh+/Rh–. An Rh-negative person has a genotype of Rh–/Rh–. A blood transfusion reaction occurs when the transfused blood does not match the person's ABO blood type, and the antibodies they have present react with the antigens on the new blood cells.

Sex and Life Span Considerations ⬆ ⬇

Newborns do not form antibodies to ABO blood group antigens during the first 3 months of life. Infants older than 3 to 4 months and older adults are more likely to experience problems of fluid overload with transfusion, and children are more likely to develop transfusion-related HIV infections than are adults. The incidence of transfusion reactions does not appear to be based on gender, although nonhemolytic febrile reactions and extravascular hemolytic reactions are more common in females who have been pregnant.

Health Disparities and Sexual/Gender Minority Health ⬆ ⬇

DHTR occur in patients who have received previous transfusions. They are particularly serious and potentially life threatening for people with sickle cell disease, a blood disorder common in Black people of African origin. They may occur because of differences in red blood cell antigens in White blood donors and Black blood recipients, leading to transfusion reactions and hemolysis. Sexual and gender minority status has no known effect on the risk for transfusion reaction.

Global Health Considerations ⬆ ⬇

No data are available, but blood transfusion reactions have the potential to occur at any location where blood products are administered.

Assessment ⬆ ⬇

ASSESSMENT

History

Individuals who report a history of numerous allergies or previous transfusions should be monitored more carefully because they are at higher risk for transfusion reaction. A history of cardiovascular disease should be noted because those patients need to be monitored more carefully for fluid overload. Note also if a patient has a history of Raynaud syndrome or a cold agglutinin problem because, before being administered and with physician approval, the blood needs to be warmed. Once the transfusion is in process, the patient may report any of the following signs of transfusion reaction: heat or pain at the site of transfusion, fever, chills, flushing, chest tightness, lower back pain, abdominal pain, nausea, difficulty breathing, itching, and a feeling of impending doom.

Physical Examination

A change in any vital sign can indicate the beginning of a transfusion reaction. Note if the urine becomes cloudy or reddish (hemolysis). Observe any change in skin color or the appearance of hives. Be alert for signs of edema, especially in the oropharynx and face. Auscultate the lungs before beginning the transfusion, and note any baseline adventitious sounds; monitor for crackles or wheezes if the patient shows any signs of fluid overload, and inspect the patient's neck veins for distention.

Psychosocial

Blood bank protocols have lowered the risk of HIV transmission from more than 25,000 cases before 1985. Presently, only 1 in 2 million blood donations might carry HIV and transmit the disease to patients. In spite of the decreased risk, however, many patients worry about contracting HIV when they need blood products. In reality, the risk of hepatitis B and C is much higher; the risk of hepatitis B is 1 per 205,000 donations. If a blood transfusion reaction occurs, the fears and anxieties are compounded and may warrant specific interventions.

Diagnostic Highlights

In the event of a transfusion reaction, immediately stop the transfusion. Send the unit of blood, or empty bag and tubing if the infusion is complete, along with samples of the patient's blood and urine to the laboratory for analysis. Blood type and crossmatching are repeated to determine if mismatched blood was administered.

Test	Normal Result	Abnormality With Condition	Explanation
Free hemoglobin: Urine and plasma	Negative in urine < 3 mg/dL in blood	Free hemoglobin in urine and blood; hemoglobinuria occurs when > 150 mg/dL of free hemoglobin is present in blood	Transfusion reaction leads to escape of hemoglobin from red blood cells during intravascular hemolysis

Other Tests: Blood culture to rule out bacterial infection, urinalysis for presence of protein, serum bilirubin, haptoglobin, complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, calcium, serum electrolytes

Primary Nursing Diagnosis ⬆ ⬇

Diagnosis

DiagnosisRisk for ineffective airway clearance as evidenced by restlessness, wheezing, stridor, dyspnea, and/or angioedema

Outcomes

OutcomesRespiratory status: Airway patency; Respiratory status: Gas exchange; Respiratory status: Ventilation; Comfort status; Infection severity; Knowledge: Treatment regime

Interventions

InterventionsAirway management; Airway insertion and stabilization; Airway suctioning; Anxiety reduction; Oxygen therapy; Respiratory monitoring

Planning and Implementation ⬆ ⬇

PLANNING AND IMPLEMENTATION

Collaborative

Prevention.

Typing, screening, and matching of blood units before administration eliminate most, but not all, incompatibilities. If a transfusion reaction does occur, stop the transfusion immediately and replace the donor blood with normal saline solution. The severity of the reaction is usually related to the amount of blood received. Begin an assessment to determine the severity and type of reaction. In minor reactions (urticaria or fever), the transfusion may be restarted after discussion with the physician and after giving the patient an antipyretic, antihistamine, or anti-inflammatory agent. Ongoing monitoring during the rest of the transfusion is essential. If the patient develops anaphylaxis, the patient's airway and breathing are maintained with oxygen supplement, intubation, and mechanical ventilation if needed.

Pharmacologic Highlights

With an acute hemolytic reaction, there are three conditions to consider: renal failure, shock, and disseminated intravascular coagulation (DIC). To counteract shock and minimize renal failure, the physician prescribes aggressive normal saline or colloid IV infusion. Mannitol is often used to promote diuresis. Dopamine may be used if hypotension is a problem. Furosemide (Lasix) may be given to keep urine output at 50 to 100 mL/hr. For pyretic reactions, after the possibility of a hemolytic reaction is ruled out, an antipyretic such as acetaminophen may be given and the transfusion may be restarted with caution. For severe reactions, see the table that follows.

Medication or Drug Class	Dosage	Description	Rationale
Epinephrine	0.1–0.25 mg of 1:10,000 concentration IV over 5–10 min	Sympathomimetic; catecholamine	Given for severe reactions for its pressor effect and bronchodilation
Glucocorticoids	Varies by drug	Corticosteroid	Anti-inflammatory agents that limit laryngeal swelling

Other Drugs: Antihistamines may be given for minor allergic reactions, diuretics may be given to increase renal blood flow in hemolytic transfusion reactions and manage volume overload, and dopamine may be given to maintain cardiac output and renal blood flow.

Independent

Adhere strictly to the policies regarding typing, crossmatching, and administering blood. Check each unit before administration to make sure that it is not outdated, that the unit has been designated for the correct recipient, that the patient's medical records number matches the number on the blood component, and that the blood type is appropriate for the patient. All patients should have their identification band checked by two people before the transfusion is begun. Notify the blood bank and withhold the transfusion for even the smallest discrepancy when checking the blood with the patient identification. If a transfusion reaction occurs, make sure the recipient's blood sample is correctly labeled when it is sent to the laboratory. Maintain universal precautions when handling all blood products to protect yourself and dispose of used containers appropriately in the hazardous waste disposal.

Begin the transfusion at a rate of 75 mL or less per hour. Remain with the patient for the first 15 minutes of the transfusion to monitor for signs of a hemolytic reaction. If the patient develops a reaction, stop the transfusion immediately; evaluate the adequacy of the patient's airway, breathing, and circulation; take the patient's vital signs; notify the physician and blood bank; and return the unused portion of the blood to the blood bank for analysis. If the patient develops chills, monitor the patient's temperature and cover the patient with a blanket unless the temperature is above 102°F (38.9°C). Remain with the patient and explain that a reaction has occurred from the transfusion. If the patient has excessive fears or concerns about the risk of HIV or hepatitis infection, provide specific information to the patient and arrange for a consultation as needed with either a physician or a counselor.

Evidence-Based Practice and Health Policy

Shmookler, A., & Flanagan, M. (2020). Educational case: Febrile nonhemolytic transfusion reaction. Academic Pathology. Advance online publication. https://doi.org/10.1177/2374289520934097

The authors described a case study of a 34-year-old woman who came to the emergency department because of lightheadedness and dizziness. She had a low hemoglobin (6.5 g/dL) and hematocrit (18.5%). Her physician prescribed the transfusion of a unit of red blood cells. Thirty minutes into the transfusion, the patient developed chills and fever.
The transfusion was stopped immediately. Following a clinical assessment to determine that the patient was stable, the blood bank was alerted to ensure that the appropriate blood product was transfused to the appropriate patient. Following laboratory analysis of the patient's blood and urine, it was determined that she had a febrile nonhemolytic transfusion reaction, which has a risk of 3 per 100 transfusions. Ultimately after further laboratory work, the patient received a different unit of blood without reaction.

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DRG Information ⬇

Introduction ⬆ ⬇