Patients with acute blood loss or symptomatic anemia frequently require blood replacement therapy in the emergency department. Although blood replacement therapy is generally safe, it should be understood that certain risks accompany the transfusion of blood and plasma components. Accordingly, emergency physicians must be familiar with and be able to manage adverse transfusion reactions, ranging from self-limited febrile responses to life-threatening intravascular hemolysis.
Adverse reactions can occur in any blood transfusion recipient, but are more common in patients with hematologic and oncologic diseases. They can be categorized as immunologic, infectious, chemical, and physical; some also subdivide these reactions into acute and delayed types.
The "classic" transfusion reactions are immunologic in nature and result from the interaction(s) of inherited or acquired antibodies with foreign antigens associated with cellular or humoral components of transfused blood products.
The major blood transfusion reactions are as follows:
- Immediate Adverse Reactions
- Immune-Mediated Hemolytic Reaction
- Other Nonimmune Causes Of Hemolysis
- Febrile Nonhemolytic Reaction
- Anaphylactic Reaction
- Allergic Reactions
- Bacterial Contamination
- Graft-versus-host disease (GVHD)
- INFECTIOUS DISEASE
- Transfusion-Associated Hepatitis
- Cytomegalovirus (CMV)
- Acquired Immunodeficiency Syndrome (AIDS)
- OTHER PROBLEMS
- Iron Overload
- Citrate Toxicity
IMMEDIATE ADVERSE REACTIONS:
1. Immune-Mediated Hemolytic Reaction:
Hemolytic transfusion reaction is the immunologic destruction of transfused red cells, nearly always due to incompatibility of antigen on the transfused cells with antibody in the recipient’s circulation. The most common cause of severe, acute hemolytic reactions is transfusion of ABO-incompatible blood, resulting from identification errors occurring at some point(s) in the transfusion process. Serologic incompatibility undetected during pretransfusion testing is a much less common cause of acute hemolysis.
Signs and Symptoms
The patient may have fever, chills, chest pain, hypotension, or nausea. Other signs and symptoms are dyspnea, pain at the infusion site or in the back, hemoglobinuria, and shock. The only sign in the anesthetized patient maybe hypotension, generalized bleeding, or oozing at venipuncture sites. The reaction may occur after a small amount of blood has been infused, and symptoms may range from mild to severe. The most severe hemolytic reactions are due to ABO mismatch. A serologic investigation may be of help in determining the cause of the reaction.
Investigation if a hemolytic reaction is suspected:
- Stop the transfusion. Maintain vascular access with saline infusion.
- Notify physician, and initiate transfusion reaction workup.
- At the bedside, examine blood bag slip, blood label, and patient identification to determine if a clerical error has occurred.
- Send post transfusion blood samples to the laboratory. Laboratory tests that may be useful in monitoring the patient's condition include post transfusion hemoglobin and hematocrit, urine free hemoglobin, free hemoglobin in plasma or serum, unconjugated bilirubin (5-7 hours post transfusion), and serum haptoglobin on pre and post reaction specimens. To establish baseline renal values, measure blood urea nitrogen (BUN), creatinine, and a 24-hour urine collection. To monitor the occurrence of disseminated intravascular coagulation, order platelet count, prothrombin time, partial thromboplastin time, fibrinogen, fibrin split products, or other coagulation studies.
The first test for determining red cell destruction is a comparison of the pre- transfusion and post transfusion sera. Increased pink color may be indicative of free hemoglobin. Also, a direct antiglobulin test on the post transfusion sample will determine if antibody-coated cells remain in the circulation.
Other tests include repeating ABO, Rh, antibody screen, and compatibility tests on the patient's sample and donor unit. In addition to the bedside check, a thorough clerical check in the laboratory is necessary to make sure there is no misidentification of samples.
There are no large series or controlled studies of the treatment of hemolytic reaction, and most treatment is based on supportive care until recovery from the sequelae occurs. Therapy of the acute hemolytic reaction consists of maintaining BP and urinary output. Maintain urine flow of at least 100 ml/hour for 18-24 hours. Although mannitol has been used in the management of hemolytic reactions, furosemide, 80-120 mg IV, will improve renal blood flow and result in diuresis.
2. Other Nonimmune Causes Of Hemolysis
- Disseminated intravascular coagulation (DIC):If DIC occurs as a result of acute hemolysis, heparin is indicated if the severity of the condition warrants treatment. Adults may be given 50—100 mg of sodium heparin IV followed by continuous IV infusion of 250-350 mg of heparin for 24 hours. Prompt recognition and treatment are necessary. Cryoprecipitate is a source of fibrinogen and may be given to maintain fibrinogen levels at approximately 100 mg/dl.
- Oliguria: Patients developing oliguria will require close management of fluid and electrolytes and may require dialysis.
3. Febrile Nonhemolytic Reaction
- Mechanical hemolysis: Red cells may be traumatized by excess heat, inadvertent freezing, small-caliber needles, or infusion under pressure.
- Incompatible fluid: Osmotic lysis of red cells may occur if blood comes in contact with hypotonic fluid, such as 5% dextrose and water.
Febrile nonhemolytic reaction is typically manifested by a temperature elevation of ≥ 1 C or 2 F occurring during or shortly after a transfusion and in the absence of any other pyrexic stimulus. This may reflect the action of antibodies against white cells or the action of cytokines, either present in the transfused component or generated by the recipient in response to transfused elements. Febrile reactions may accompany about 1% of transfusions; and they occur more frequently in patients previously alloimmunized by transfusion or pregnancy. One proposed mechanism for this reaction is antibodies in the recipient that react with donor leukocytes or platelet antigens.
Signs and symptoms
In addition to fever, patients may experience shaking chills. The temperature rise may be mild or severe and may occur during or after the transfusion. In severe reactions, hypotension, cyanosis, and tachypnea may occur.
Diagnosis and treatment
4. Anaphylactic Reaction
Signs and symptoms
A serologic evaluation may be necessary to rule out a hemolytic transfusion reaction. Fever and discomfort may be prevented by premedication with antipyretics prior to transfusion. The patient with severe reactions who requires ongoing transfusion support may benefit from both premedication and a leukocyte-poor blood product.
The striking feature of this reaction is its sudden onset, occurring after the patient receives a few milliliters of the transfusion. Fever is often absent. Coughing, respiratory distress, hypotension, nausea, abdominal pain, vomiting, diarrhea, shock, or loss of consciousness may occur.
Diagnosis and treatment
This type of transfusion reaction always requires prompt, efficient therapeutic intervention. Frequently, the patient may require generous amounts of IV fluid to correct the hypotension. Epinephrine (0.3-0.5 ml) either SQ or IV may be necessary to reverse acute anaphylactic symptoms. Corticosteroids given IV may also help improve the clinical status. The reaction occurs in the IgA-deficient patient with anti-IgA antibodies. These patients may receive blood from IgA-deficient donors, frozen deglycerolized red blood cells, or autologous transfusion.
5. Allergic Reaction
Limited cutaneous reactions may occur as a result of transfusion.
These symptoms respond to treatment with antihistamines, diphenhydramine, 50 mg, administered PO or parenterally. If the hives and itching are controlled and no other symptoms are present, the transfusion may be continued. A washed red cell product may benefit the patient with severe reactions.
Signs and symptoms:
The patient receiving a transfusion may start itching and develop erythema or hives. One proposed mechanism is the presence of allergens in the donor's plasma.
6. Bacterial Contamination
The organisms that grow in blood products are gram-negative bacteria including Pseudomonas, Citrobacter freundii, and Escherichia coli.
Signs and symptoms
A patient receiving a bacterially contaminated product may develop high fever, shock, hemoglobinuria, disseminated intravascular coagulation, and renal failure. The clinical presentation may resemble septic shock. Other systemic findings including cramps, muscle pain, nausea, vomiting, and diarrhea may occur.
Diagnosis and treatment
7. Transfusion-Related Acute Lung Injury (TRALI)
If contamination is suspected, the units may be cultured, and a Gram's stain should be done on the donor unit and the unit cultured. The patient's blood should be cultured for aerobic and anaerobic organisms. Contamination can be life-threatening and requires immediate treatment with antibiotics and corticosteroids (methylprednisolone).
TRALI occurs when acutely increased permeability of the pulmonary microcirculation causes massive leakage of fluids and protein into the alveolar spaces and interstitium, usually within 6 hours of transfusion. In many cases, the occurrence of TRALI is associated with the presence of granulocyte antibodies in the donor or recipient. The specific mechanism of action is not clear. Treatment consists of aggressive respiratory support.
8. Post Ransfusion Purpura (PTP)
PTP is a rare syndrome characterized by the development of dramatic, sudden, and self-limiting thrombocytopenia, typically 7-10 days after a blood transfusion, in a patient with a history of sensitization by either pregnancy or transfusion. While the immune specificity may be to a platelet specific antigen the patient lacks, autologous and allogeneic platelets are destroyed. In a bleeding patient, high dose Immune Globulin Intravenous (IGIV) may promptly correct the thrombocytopenia.
9. Graft-versus-host disease (GVHD)
GVHD is a rare but extremely dangerous condition that occurs when viable T lymphocytes in the transfused component engraft in the recipient and react against tissue antigens in the recipient. GVHD can occur if the host does not recognize as foreign and reject the transfused cells, and can follow transfusion of any component that contains even very small numbers of viable T lymphocytes.
Severely immunocompromised recipients are at greatest risk (e.g., fetuses receiving intrauterine transfusions, recipients of transplanted marrow or peripheral blood progenitor cells, and selected patients with severe immunodeficiency conditions), but GVHD has been reported in immunologically normal recipients heterozygous for a tissue antigen haplotype for which the donor is homozygous. This is most likely to occur when the transfused component is from a blood relative or has been selected for HLA compatibility. GVHD remains a risk with leukocyte-reduced components because they contain sufficient residual T lymphocytes. Irradiation of the component renders T lymphocytes incapable of proliferation and is presently the only approved means to prevent GVHD.
Signs and symptoms
The patient develops a skin rash, diarrhea, liver dysfunction, and/or marrow suppression.
Diagnosis and treatment
Biopsies from the involved areas may be needed to distinguish this from other clinical conditions, and even with biopsy material, uncertainty remains. The treatment of GVH is investigational, but immunocompromised patients at risk for developing GVH should receive irradiated blood products. Lymphocytes in blood products receiving a radiation dose of 1500-5000 rads will not replicate, but the function of red cells, platelets, and granulocytes is maintained.
1. Transfusion-Associated Hepatitis:
It is a serious complication of blood transfusion. Donor blood is screened for hepatitis B surface antigen, but a number of transfusion-associated cases still exist.
Non-A, non-B hepatitis accounts for the majority of cases of transfusion-associated hepatitis. There is a variable clinical picture. Other patients develop weakness, nausea, joint pain, and malaise a few weeks or months following transfusion. The disease may progress, with patients developing increased jaundice, weakness, nausea, and vomiting. Liver enzymes are markedly elevated. In most patients, recovery from non-A, non-B hepatitis begins in a few weeks; however, a certain percentage may develop chronic liver disease.
- The physician should contact the blood bank when he suspects a case of transfusion-associated hepatitis. The donor units may be identified and implicated donors identified.
- The incubation period varies from 2 weeks-4 months, with a median of 2 months.
- The majority of patients are asymptomatic, and the diagnosis is made only as serial transaminase levels are measured. Twenty percent of patients develop jaundice usually 1—4 weeks after the elevation of transaminase levels.
- Additional testing of donor blood including alanine aminotransferase (ALT) and hepatitis B core antigen is being considered as a surrogate test until a more specific method for screening units is available.
This may be transfusion acquired, and this is a special concern for the neonate and the immunocompromised patient. There is no ideal test to determine CMV infectivity of donor blood, but many centers offer CMV antibody-negative units.
3. Acquired Immunodeficiency Syndrome (AIDS)
Several hundred cases of HIV (human immunodeficiency virus) transmission have resulted from blood transfusion .The incidence of disease is expected to increase because of the long incubation period. The blood donation health questionnaire includes questions about whether the individual belongs to a high-risk group and has the signs and symptoms of the prodrome or the disease. Donor blood is tested for HIV antibody, and this testing has improved the safety of the blood supply.
Transfusion-associated malaria is rare .It is prevented by excluding donors who have been in malaria endemic areas. Syphilis can be transmitted by transfusion, but this is rare. It occurs from products stored at room temperature or those infused shortly after donation from a donor with spirochetemia.
When a patient rapidly receives large quantities of blood and other fluids, circulatory overload may result.
Signs and symptoms
The onset of signs and symptoms may be acute or delayed. They include nonproductive cough and tachycardia followed by dyspnea, cyanosis, and pulmonary edema.
When fluid balance is uncertain, the massively transfused patient should be monitored by central venous pressure. If fluid overload occurs, the emergency treatment consists of stopping the transfusion, giving oxygen, and performing a therapeutic phlebotomy.
Patients with congestive heart failure, edema, or altered renal function may not be able to tolerate added volume, yet require red cell transfusion. These patients should receive packed red cells. The transfusion should be slow. An acceptable rate may be 1 ml/kg of body weight/hour.
2. Iron Overload
Chronically transfused patients, particularly those with P thallassemia, sideroblastic anemia, and aplastic anemia, are at risk for iron overload. The daily excretion of iron is 1—2 mg/day. One unit of red cells contains approximately 250 mg of iron. The excess iron accumulates in the heart, liver, and endocrine organs.
Signs and Symptoms:
Signs of transfusion-related iron overload include cardiac arrhythmia or failure, hepatic dysfunction and cirrhosis, abnormal glucose tolerance tests, and/or diabetes. An elevated serum iron-binding capacity helps to make the diagnosis in the patient with a long-term history of transfusions.
The patient may receive chelating agents to remove iron without decreasing his or her hemoglobin, but because of the amount of iron received compared to the amount that can be removed by chelating agents, the problem of iron overload is only delayed.
3. Citrate Toxicity
This is a complication of massive transfusion. The citrate present within the anticoagulant of the banked blood is given to the patient during the transfusion and is normally metabolized by the liver. When liver function is impaired or overloaded, the citrate binds ionized calcium in the patient's blood and lowers plasma levels of ionized calcium, causing involuntary muscle tremors or cardiac dysfunction. Citrate toxicity is reversed by the intravenous administration of calcium gluconate, 4.5 mEq of calcium (10 ml of 10% calcium gluconate) per liter of citrated blood. There are many variables present that affect the individual’s response to massive transfusion. Hypothermia and potassium levels may play a role in the patient's response to citrate.