Immunological Complications

63

Table 11.2 Immune red cell destruction. Site of destruction Characteristics lytic of antibodies Red cell ruptures Predominantly intravascular Potent, Predominantly extravascular

Antibodies that do not activate or only partially activate complment (Anti-Rh, anti-K, anti-Jk, and others) Nausea, shivering

(Anti-A and -B) Substernal pain, lumbar pain, restlessness uncontrollable bleeding Haemoglobinuria

Haemoglobin liberated into plasma Figure 11.1 IgM anti-A binding to two adjacent A sites activtes th whole of complment pathway (C1 to C9); C8 and C9 make holes in th red cell membrane.

Symptoms

Signs: Immdiate

Hypotension, fever,

Fever

Jaundice

\ I g IgG anti-Rh

Later

. Rh sites Red cells lysed / Antibody coated red cells I \

antigen (anti-HLA) - do not activate

within macrophage; haemoglobin metabolised Bilirubin liberated

Red cells adhres to, and is lysed outside, macrophage

Red cells adhres to, and is lysed outside, killer lymphocyte Haemoglobin liberated

Haemoglobin liberated Figure 11.2 IgG anti-Rh does not activate complment. Red cells coated with antibody adhre to a macrophage or killer lymphocyte and are either ingested or lysed at th cell surface.

incompatible blood are unconscious at th time, so that there are no symptoms that might call attention to what is happening.

Mechanisms of red cell destruction

When ABO incompatible red cells are transfused - for example donor group A and rcipient group O - th incompatible IgM antibody (anti-A and anti-AB in this case) immediately binds to th donor's red cells (Figure 11.1). The bound antibody activtes complment leading to immdiate lysis of donor red cells in th plasma. When th antibody is potent, virtually ail th transfused red cells may be lysed within th bloodstream. Many other blood group allo-antibodies, leading to immdiate haemolytic reactions, are IgG and activate complment, but as a rule they do so only partially, up to C3b, and th coated cells, after binding to monocytes/macrophages, are either ingested or destroyed by cytotoxicity as they pass through th liver and spleen. Some antibodies - for example anti-Rh and a few anti-human leucocyte

complment (Figure 11.2), and thse cause macrophages to remove coated red cells or platelets in th spleen only.

Symptoms and signs The vast majority of patients experiencing an ABO incompatible transfusion reaction hve no symptoms. However, about 20-25% of patients, particularly if group O, will hve symptoms of vary-ing severity (Table 11.2). In th conscious patient, th transfusion of even a few millilitres of ABO incompatible blood may cause symptoms within 1 or 2 minutes. The patient becomes restless and complains of a feeling of oppression that is often accompanied by substernal pain, chills and fever. The patient may also complain of a burning face and may hve abdominal pain and may vomit. In th unconscious patient th most important signs are hypotension and uncontrollable bleeding. The main cause of th symptoms and of th hypotension is th release of th products of complment (C3a and C5a) into th plasma. Thse are polypeptides with a molecular weight of about 20000, which cause th contraction of smooth muscle and th production of nitric oxide, oxygen radicals and cytokines such as tumour necrosis factor (TNF) and interleukin-1 (IL-1); they also cause degranulation of mast cells leading to th release of vasoac-tive substances (bradykinin and serotonin). Bleeding is caused by disseminated intravascular coagulation, which is thought to be triggered by procoagulant substances released from red cell stroma after lysis and also, possibly, by th direct activation of th coagulation System by complment, by antigen-antibody complexes and by cytokines. Oliguria is common after th transfusion of ABO incompatible blood and is thought to be th resuit of changes in rnal blood fiow precipitated by hypotension, rather than haemoglobinuria (Box 11.5). As soon as it is suspected that incompatible blood has been transfused, th transfusion should be stopped, and an intra-venous infusion of crystalloid solution should be started to maintain urinary output. Frusemide 80-200 mg should be given