Autoimmune haemolytic anaemia
Acquired haemolytic anaemia is due to immunological destruction of red blood cells mediated by autoantibodies directed against antigens on the patient’s red blood cells. Autoimmune haemolytic anaemia is classified according to whether the antibody reacts best at body temperature (warm antibodies) or at lower temperatures (cold antibodies) (Table 5.11). IgG or IgM antibodies attach to the red cell, resulting in extravascular haemolysis
Table 5.11 Features of autoimmune haemolytic anaemia
Temperature at which antibody attaches best to red cell
Lower than 37 °C
Type of antibody
Direct Coombs’ test
Autoimmune disorders, e.g. SLE
Infections e.g. Mycopiasma spp.
Many drugs, e.g. methyldopa
SLE, systemic iupus eiythematosus, CLL, chronic iymphocytic ieukaemia.
through sequestration in the spleen, or in intravascular haemolysis through activation of complement. The autoimmune haemolytic anaemias are diag-nosed on the basis of a positive direct antiglobulin (Coombs') test. This is a test for antibodies or complement attached to the surface of red blood cells. The red blood cells of the patient are reacted with antiserum or monoclonal antibodies prepared against the various immunoglobulins and the third com-ponent of complement (C3d). If either or both of these are present on the red cell surface, agglutination of red cells will be detected.
‘Warm’ autoimmune haemolytic anaemia
This anaemia occurs at all ages in both sexes, with a variable clinical picture ranging from mild haemolysis to life-threatening anaemia. It may be primary or secondary (Table 5.11).
There is evidence of haemolysis (p. 205) and direct Coombs' test is positive.
High-dose steroids (e.g. prednisolone 1 mg/kg daily) induce remission in 80% of cases. Splenectomy is useful in those failing to respond to steroids.
Occasionally, immunosuppressive drugs such as azathioprine and rituximab are beneficial.
‘Cold’ autoimmune haemolytic anaemia
IgM antibodies (cold agglutinins) attach to red cells in the cold peripheral parts of the body and cause agglutination and complement-mediated intra-vascular haemolysis. After certain infections e.g. Mycoplasma, Epstein-Barr virus, there is increased synthesis of cold agglutinins (normally produced in insignificant amounts) and transient haemolysis. A chronic idiopathic form occurs in elderly people, with recurrent haemolysis and peripheral cyanosis.
There is evidence of haemolysis (p. 205), and direct Coombs' test is positive. Examination of a peripheral blood film at room temperature shows red cell agglutination.
Treatment is usually that of the underlying condition and avoiding exposure to cold.
Two types of mechanisms have been identified:
■ In the commonest form, the drug may associate with structures on the red cell membrane and thus be part of the antigen in a haptenic reaction. There is severe complement-mediated intravascular haemolysis which resolves quickly after drug withdrawal.
■ The drug may induce a subtle alteration of one component of the red cell membrane, rendering it antigenic. There is extravascular haemolysis and a protracted clinical course.
The mechanisms for drug-induced haemolytic anaemia probably also apply to drug-induced thrombocytopenia and neutropenia.
Non-immune haemolytic anaemia
Paroxysmal nocturnal haemoglobinuria
There is an inability to produce the glycosylphosphatidylinositol (GPI) anchor, which tethers several proteins to the cell membrane. Deficiency of two of these proteins, CD59 (membrane inhibitor of reactive lysis) and CD55 (decay-accelerating factor), renders the red cell exquisitely sensitive to the haemo-lytic action of complement. The clinical manifestations of this rare disease are related to abnormalities in haemopoietic function including intravascular haemolysis, venous thrombosis and bone marrow aplasia. Progression to myelodysplasia and acute leukaemia can also occur. Paroxysmal nocturnal haemoglobinuria should be considered in any patient with chronic or episodic haemolysis. Diagnosis is made by demonstrating deficiency of the GPI-anchored proteins on haematopoietic cells by flow cytometry. Treatment is supportive and with eculizumab, a monoclonal antibody that binds to the C5 component of complement and prevents its activation and reduces haemo-lysis. BMT has been successful in selected patients.
Mechanical haemolytic anaemia
Red cells may be injured by physical trauma in the circulation. Examples of this form of haemolysis include:
■ Leaking prosthetic heart valves: damage to red cells in their passage through the heart
■ March haemoglobinuria: damage to red cells in the feet from prolonged marching
■ Microangiopathic haemolysis: fragmentation of red cells in abnormal microcirculation caused by malignant hypertension, haemolytic-uraemic syndrome or disseminated intravascular coagulation (DIC).
1. Ethics and communication
2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
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