The safety of blood transfusion depends on meticulous attention to detail at each stage leading to and during the transfusion. Prevention of simple errors involving patient and blood sample identification would avoid most serious naemolytic transfusion reactions, almost all of which volve the ABO system. About 50% of fatalities associled with blood transfusion are due to immediate haernovtic transfusion reactions; the remainder are mainly due post-transfusion hepatitis.
Pretransfusion compatibility testing
1 Blood grouping. The ABO and RhD groups of the patient are determined.
2 Antibody screening. The patient’s serum is screened for atypical antibodies that may cause a significant reduction in the survival of the transfused red cells. The patient’s serum is tested against red cells from at least two Group 0 donors, expressing a wide range of red cell antigens, for detection of IgM red cell alloantibodies (using a direct agglutination test of cells suspended in saline) and IgG antibodies (using an indirect antiglobulin test). If there is a positive result, the blood group specificity of the antibody should be determined using a comprehensive panel of typed red cells.
3 Donor blood of the same ABO and RhD group as the patient is selected.
(a)Patients without atypical red cell antibodies. The full crossmatch involves testing the patient’s serum against the donor red cells suspended in saline in a direct agglutination.test and also using an indirect antiglobulin test. In some hospitals this has been shortened to an immediate spin crossmatch where the patient’s serum is briefly incubated with the donor red cells, followed by centrifugation and examination for agglutination; this rapid crossmatch is an acceptable method of excluding ABO incompatibility in patients known to have a negative antibody screen.
(b) Patients with atypical red cell antibodies; Donor blood lacking the relevant red cell antigen(s), as well as being the same ABO and RhD group as the patient should be selected. A full cross match should always be carried out.
Many hospitals have guidelines for blood ordering for elective surgery (maximum surgical blood ordering schedules), aiming to reduce unnecessary crossmatching and the amount of blood that eventually becomes outdated. Many operations in which blood is only occasionally required for unexpectedly high blood loss can be classified as ‘group and save serum’; this means that, where the antibody screen is negative, blood is not reserved in advance but can be made available quickly if necessary. If a patient has atypical antibodies, compatible blood should always be reserved in advance.
The complications of blood transfusion
ALLOIMMUNIZATION. All transfusions carry a risk of immunization to the many antigens present on red cells, leucocytes, platelets and plasma proteins. Alloimrnunization does not usually cause clinical problems with the first transfusion but these may occur with subsequent transfusions. There may also be important delayed consequences of alloimmunization such as HDN and rejectionof tissue transplants.
INCOMPATIBILITY. This may result in poor survival of transfused cells, such as red cells and platelets, and also in the harmful effects of antigen-antibody reaction. Haemolytic transfusion reactions.
IMMEDIATE. This is the most serious complication of blood transfusion and is usually due to ABO incompatibility. There is complement activation by the antigenantibody reaction, usually due to IgM antibodies, leading to rigors, lumbar pain, dyspnoea, hypotension, haernoglobinuria and renal failure. Activation of coagulation may also occur; bleeding due to disseminated intravascular coagulation (DIe) is a bad prognostic sign. Emergency treatment may be needed to maintain the blood pressure and renal function.
The diagnosis is confirmed by finding evidence of haemolysis, such as haemoglobinuria, and incompatibility between donor and recipient. All documentation should be checked to detect errors such as:
• Failure to confirm the identity of the patient when taking the sample for compatibility testing, i.e. sample taken from the wrong patient
• Mislabelling the blood sample with the wrong patient’s name
• Simple labelling or handling errors in the laboratory
• Failure to perform proper identity checks before the blood is transfused, i.e. blood transfused to the wrong patient
The blood grouping of the patient’s sample (used for the original compatibility testing), a new sample taken from the patient after the reaction and the donor units should all be checked to confirm where the error occurred. The serious consequences of such failures emphasize the need for meticulous checks at all stages in the procedure of blood transfusion.
At the first suspicion of any transfusion reaction the transfusion should always be stopped and the donor units returned to the blood transfusion laboratory with a new blood sample from the patient to exclude a haemolytic transfusion reaction.
DELAYED. This may occur in patients alloimmunized by previous transfusions or pregnancies. The antibody level is too low to be detected by pretransfusion compatibility testing but a secondary immune response occurs after transfusion, resulting in destruction of the transfused cells, usually by IgG antibodies.
Haemolysis is usually extravascular and the patient may develop anaemia and jaundice about a week after the transfusion, although most are clinically silent. The blood film shows spherocytosis and reticulocytosis. The direct antiglobulin test is positive and detection of the antibody is usually straightforward.
Non-haemolytic (febrile) transfusion reactions
Febrile reactions are a common complication of blood transfusion in patients who have previously been transfused or pregnant. The usual cause is the presence of leucocyte antibodies in the recipient acting against transfused leucocytes, leading to release of pyrogens. Typical signs are flushing and tachycardia, fever (>38°C), chills and rigors. Aspirin may be used to reduce the fever, although it should not be used in patients with thrombocytopenia. Febrile reactions may be prevented after further transfusions by the use of leucocyte-depleted blood.
Potent leucocyte antibodies in the plasma of donors, who are usually multiparous women, may cause severe pulmonary reactions (called transfusion-related acute lung injury or TRALI) characterized by dyspnoea, fever, cough, and shadowing in the perihilar and lower lung fields on the chest X-ray.
Urticaria and anaphylaxis
Urticarial reactions are often attributed to plasma protein incompatibility but, in most cases, they are unexplained. They are common but rarely severe; stopping or slowing the transfusion and administration of chlorpheniramine 10 mg i.v. are usually sufficient treatment.
Anaphylactic reactions occasionally occur;
severe reactions are seen in patients lacking 19A who produce anti-lgA that reacts with IgA in the transfused blood. The transfusion should be stopped and adrenaline 0.5 mg i.m. and chlorpheniramine 10 mg i.v. should be given immediately; endotracheal intubation may be required. Patients who have had severe urticarial or anaphylactic reactions should receive either washed red cells, autologous blood or blood from 19A-deficient donors for patients with IgA deficiency.
Transmission of infection
The incidence of post-transfusion hepatitis was estimated to be about 1% in the UK before testing for antibodies against hepatitis C virus (HeV) was introduced in 1991. As most cases were due to non-A, non-B hepatitis due to Hev, the incidence of post-transfusion hepatitis is expected to decrease. Each donation has been tested for HBsAg for many years and the incidence of post-transfusion hepatitis due to hepatitis B is very low. Other viruses which may cause post-transfusion hepatitis include CMV, EBV and other as yet unidentified viruses. In the UK the incidence of transmission of HIV by blood transfusion is extremely low, probably in the order of one in one million units. Prevention is based on selfexclusion of donors in ‘high-risk’ groups and testing each donation for anti-HIV. There is an increased risk of transmission of hepatitis viruses and HIV from coagulation factor concentrates prepared from large pools of plasma. However, these are now subjected to measures for inactivating viruses such as treatment with heat, solvents and detergents. The problem of viral transmission is still a major problem in the developing world.
Transfusion-transmitted syphilis is now very rare in the UK. Spirochaetes do not survive for more than 72 hours in blood stored at 4°C and each donation is tested using the Treponema pallidum haemagglutination assay (TPHA).
An alternative to the use of blood from volunteer donors for the replacement of blood lost during surgery is the patient’s own blood. Interest in autologous transfusion was mainly stimulated by concern about transmission of infection, especially HIV, by blood transfusion. There are three types:
1 Pre-deposit. The patient donates 2-5 units of blood at approximately weekly intervals before elective surgery.
2 Preoperative haemodilution. One or two units of blood are removed from the patient immediately before surgery and retransfused to replace operative losses.
3 Blood salvage. Blood lost during or after surgery may be collected and retransfused. Several techniques of varying levels of sophistication are available. The operative site must be free of bacteria, bowel contents and tumour cells.
There has been little demand for autologous transfusion in the UK as blood is generally perceived as being ‘safe’. In addition, there would be considerable costs in setting up a predeposit autologous transfusion service, which would only benefit a minority of patients. In developing countries, however, autologous blood and blood from relatives is increasingly being used.