Patients with acute blood loss or symptomatic anaemia 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 staff must be familiar with and be able to manage adverse transfusion reactions, ranging from self-limited febrile responses to life-threatening intravascular haemolysis.

Adverse reactions can occur in any blood transfusion recipient, but are more common in patients with haematologic and oncologic diseases. They can be categorized as immunologic, infectious, chemical and physical; some also subdivide these reactions into acute and delayed types.

The major blood transfusion reactions are as follows:

Haemolytic reaction is the immunologic destruction of transfused red cells, nearly always due to incompatibility of the antigen on the transfused cells with the antibody in the recipient's circulation. The most common cause of severe, acute haemolytic reactions is transfusion of ABO-incompatible blood, resulting from identification errors occurring at some point(s) in the transfusion process.

The patient may have fever, chills, chest pain, hypotension, nausea, dyspnoea, pain at the infusion site or in the back, haemoglobinuria and shock. The only sign in the anaesthetized patient maybe hypotension, generalized bleeding or oozing at the venipuncture sites. The reaction may occur after a small amount of blood has been infused, and the symptoms may range from mild to severe. A serologic investigation may be of help in determining the cause of the reaction.

The first test for determining red cell destruction is a comparison of the pre-transfusion and post-transfusion sera. Increased pink colour may be indicative of free haemoglobin. 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.

Most treatment is based on supportive care until recovery from the sequelae occurs. Therapy of the acute haemolytic reaction consists of maintaining the blood pressure (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 haemolytic reactions, furosemide, 80-120 mg intravenous (I.V.), will improve renal blood flow and result in diuresis.

Febrile non-haemolytic reaction is typically manifested by a temperature elevation of ≥1°C and 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 the transfused elements. Febrile reactions may accompany about 1% of transfusions; they occur more frequently in patients previously allo-immunized by transfusion or pregnancy.

In addition to fever, patients may experience shaking chills. In severe reactions, hypotension, cyanosis, and tachypnoea may occur.

A serologic evaluation may be necessary to rule out a haemolytic 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 leucocyte-poor blood product.

The striking feature of this reaction is its sudden onset, occurring after the patient receives a few millilitres of the transfusion. Fever is often absent. Coughing, respiratory distress, hypotension, nausea, abdominal pain, vomiting, diarrhoea, cardiac arrhythmia, shock, cardiac arrest or loss of consciousness may occur.

This type of transfusion reaction always requires prompt, efficient therapeutic intervention. Frequently, the patient may require generous amounts of I.V. fluid to correct the hypotension. Epinephrine (0.3-0.5 ml) either sub-cutaneous (SQ) or I.V. may be necessary to reverse acute anaphylactic symptoms. Corticosteroids given by I.V. may also help improve the clinical status.

Seen in approximately 1% of recipients and caused by foreign plasma proteins. On rare occasions they may be associated with laryngeal oedema and bronchospasm.

The patient receiving a transfusion may start itching and develop erythema or hives.

These symptoms respond to treatment with antihistamines, such as 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.

Bacteria may be introduced into the pack at the time of blood collection from sources such as donor skin, donor bacteraemia or equipment used during blood collection or processing. Bacteria may multiply during storage. Gram-positive and Gram-negative organisms have been implicated.

A patient receiving a bacterially contaminated product may develop high fever, shock, haemoglobinuria, disseminated intravascular coagulation and renal failure. The clinical presentation may resemble septic shock. Other systemic findings, including cramps, muscle pain, nausea, vomiting and diarrhoea, may occur.

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.

Symptomatic support for respiratory distress includes oxygen administration and may require intubation and mechanical ventilation. Symptoms generally resolve over 24-48 hours.

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 that the patient lacks, autologous and allogeneic platelets are destroyed. In a bleeding patient, high-dose immune globulin I.V. (IGIV) may promptly correct the thrombocytopenia.

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 rejects the transfused cells, and can follow the transfusion of any component that contains even very small numbers of viable T-lymphocytes.

The patient develops a skin rash, diarrhoea, liver dysfunction and/or marrow suppression.

Biopsies from the involved areas may be needed to distinguish this from other clinical conditions. The treatment of GVHD is investigational, but immunocompromised patients at risk for developing GVHD should receive irradiated blood products. Lymphocytes in blood products receiving a radiation dose of 1,500-5,000 rads will not replicate, but the function of the red cells, platelets and granulocytes is maintained.

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 and Non-B hepatitis account for the majority of cases of transfusion- associated hepatitis. 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 and non-B hepatitis begins in a few weeks; however, a certain percentage may develop chronic liver disease.

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 centres offer CMV antibody-negative units.

Several hundred cases of HIV (human immunodeficiency virus) transmission have resulted from blood transfusion. The incidence of the disease is expected to increase because of the long incubation period. 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 spirochaetaemia.

When a patient rapidly receives large quantities of blood and other fluids, circulatory overload may result.

The onset may be acute or delayed. They include non-productive cough and tachycardia followed by dyspnoea, cyanosis and pulmonary oedema.

When the 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, oedema or altered renal function may not be able to tolerate the 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.

Continually transfused patients, particularly those with P-thalassemia, sideroblastic anaemia and aplastic anaemia, 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 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 haemoglobin, 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.

This is a complication of massive transfusion. Citrate is the anticoagulant used in blood products. It is usually rapidly metabolised by the liver. Rapid administration of large quantities of stored blood may cause hypocalcaemia and hypomagnesaemia when citrate binds calcium and magnesium. This can result in myocardial depression or coagulopathy. Patients most at risk are those with liver dysfunction or neonates with immature liver function having rapid large volume transfusion.

Slowing or temporarily stopping the transfusion allows citrate to be metabolised. Replacement therapy may be required for symptomatic hypocalcaemia or hypomagnesaemia.