3. Complications of Blood Transfusion

The 2015 Serious Hazards of Transfusion (SHOT) Report identified 1,858 incidents and 26 death This was out of a total of almost 2.6 million blood components that were issued by the Blood Transfusion Service

• Acute haemolytic reactions • TRALI • TACO • Non haemolytic reactions • Allergic and anaphylactic reactions

acute antigen–antibody reaction is initiated by ABO or rhesus incompatibility Donor cells are destroyed by antibodies in the recipient plasma, with the resultant haemolysis leading in some cases to intravascular fibrin deposition, disseminated intravascular coagulation and renal failure.

presents with an acute respiratory distress syndrome either immediately or within 6 hours of transfusion. The plasma of donor blood can contain leucocyte antibodies which target recipient neutrophils Within the pulmonary microvasculature there is destruction of capillary endothelium by oxygen free radicals and proteolytic enzymes, with resultant exudation of fluid and proteinaceous material into the alveoli and the development of pulmonary oedema lower). TRALI is more likely in response to blood products with a high plasma component such as fresh frozen plasma (FFP), platelets and cryoprecipitate, and especially if the donor is female. (Human leucocyte antigen antibodies are commoner in multiparous women.) The risk is reduced by leucocyte depletion and by the use of male donors.

this was the most frequent cause of death and major morbidity in the 2015 report, being associated with seven deaths and 35 cases, respectively. It is a clinical diagnosis made when a patient develops four out of the five following symptoms within 6 hours of transfusion: acute respiratory distress, tachycardia, hypertension, pulmonary oedema positive fluid balance. Confirmation of the diagnosis is assisted if the patient responds to conventional treatments for pulmonary oedema. The SHOT report acknowledges that these diagnostic criteria lack specificity, and so they are currently under revision, and may include for example, measurements of brain-natriuretic peptide (BNP) as an indicator of myocardial stress.

Non-haemolytic (febrile) reactions: these are common and are mediated by donor leucocyte antigens which react with recipient antibodies to form a complex that binds complement and releases pyrogenic inflammatory mediators such as IL-1 and IL-6 and TNFα. Cytokines can also be introduced directly into the circulation by contaminated residual leucocytes in platelet concentrates. Leucodepletion attenuates the risk.

Allergic and anaphylactic reactions: allergic reactions to proteins in donor plasma are relatively common, are usually mild and present with typical features of pruritus and urticaria. Anaphylactic reactions are rare.

the replacement of a patient’s total blood volume within 24 hours (which is one simple definition of a massive transfusion) can affect their temperature, their biochemistry and their coagulation.

blood infused directly from storage will be at around 4 C. One litre of unwarmed blood can lower core temperature by 0.5 C. The effects of perioperative hypothermia are well known and include reduced oxygen delivery (because of the leftward shift of the oxygen–haemoglobin dissociation curve), impaired wound healing, abnormalities of coagulation increased infection rates. Hypothermia also slows enzymatic reactions so that metabolism of the citrate and lactate in stored blood is reduced.

hyperkalaemia is rarely a problem because although the potassium in stored blood can be many times higher than normal, once within the circulation intracellular re-uptake is rapid. Potassium may nonetheless rise if large volumes of blood are infused within a short time, such as in the resuscitation of patients with major trauma. However, if cold blood is infused quickly through a central venous cannula (in error) it will be cardioplegic. Stored blood contains citrate as an anticoagulant, which, when metabolized to bicarbonate in large amounts, can contribute to a metabolic alkalosis (which further impairs enzyme function). Citrate also chelates calcium, and so hypocalcaemia can be associated with the rapid infusion of large volumes of stored blood

Coagulation: plasma-reduced blood contains minimal coagulation factors which rapidly become depleted during massive transfusion. This dilutional coagulopathy may be complicated by the onset of disseminated intravascular coagulation associated with persistent haemorrhage.

: the immunosuppressive effect of homologous blood was exploited deliberately in early renal transplantation to reduce rejection rates. It is now evident that transfusion suppresses IL-2 production, killer cell activity and macrophage function. It also lowers the CD4/CD8 cell count ratio (which is the ratio of T lymphocytes that express the C4 antigen to those that express the C8 antigen, and is an indicator of the overall level of immune suppression). This immunomodulation is associated with increased rates of metastasis and tumour recurrence following surgery for colonic and other cancers, with a heightened risk of postoperative infection, and with the activation of latent chronic viral infection (such as herpes simplex).

Transmission of infection: bacterial contamination of blood and blood products is possible, and, because transfusion will ensure a large intravenous inoculum of pathogen, such contamination can result in fulminant septicaemia. (Gram-negative species thrive at the blood storage temperature of 4 C.) Viral contamination may be more insidious, and there are many recipients who are now suffering the consequences of receiving blood that at the time was unknowingly contaminated with the hepatitis B and C viruses, and with HIV. Although blood is now screened for these viruses as well as T cell lymphotrophic virus, syphilis and cytomegalovirus, there remains a transmission window during which the donor may be infected but still seronegative.

Transmission of infection: bacterial contamination of blood and blood products is possible, and, because transfusion will ensure a large intravenous inoculum of pathogen, such contamination can result in fulminant septicaemia. (Gram-negative species thrive at the blood storage temperature of 4 C.) Viral contamination may be more insidious, and there are many recipients who are now suffering the consequences of receiving blood that at the time was unknowingly contaminated with the hepatitis B and C viruses, and with HIV. Although blood is now screened for these viruses as well as T cell lymphotrophic virus, syphilis and cytomegalovirus, there remains a transmission window during which the donor may be infected but still seronegative.

Graft-versus-host disease: this is a very rare complication which can occur in recipients who are immunocompromised. Donor immune cells, particularly T lymphocytes, attack host tissue, which includes bone marrow stem cells. Ninety per cent of cases are fatal.