Haematology 2 Flashcards
(179 cards)
what causes acquired haemolytic anaemia?
due to immunological destruction of red blood cells mediated by autoantibodies directed against antigens on the patient’s red blood cells
how is autoimmune haemolytic anaemia classified?
classified according to whether the antibody reacts best at body temperature (warm antibodies) or at lower temperatures (cold antibodies)
what is the pathophysiology of autoimmune haemolytic anaemia?
Immunoglobulin (Ig) G or IgM antibodies attach to the red cell, resulting in extravascular haemolysis through sequestration in the spleen, or in intravascular haemolysis through activation of complement
what is the Coombs’ test? what can it help diagnose?
- 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 component of complement (C3d)
- if either or both of these are present on the red cell surface, agglutination of red cells will be detected
what is the temperature at which antibody attaches best to red cells in warm vs cold autoimmune haemolytic anaemia?
warm: 37C
cold: lower than 37C
what is the type of antibody in warm vs cold autoimmune haemolytic anaemia?
warm: IgG
cold: IgM
what is the direct Coombs’ test result in warm vs cold autoimmune haemolytic anaemia?
warm: strongly positive
cold: positive
what are secondary causes of warm autoimmune haemolytic anaemia?
- autoimmune disorders, e.g. SLE
- lymphomas
- CLL
- carcinomas
- many drugs, e.g. methyldopa
what are secondary causes of cold autoimmune haemolytic anaemia?
- infections e.g. Mycoplasma spp., infectious mononucleosis
- lymphomas
- paroxysmal cold
- haemoglobinuria
what are clinical features of warm autoimmune haemolytic anaemia?
- occurs at all ages in both sexes
- variable clinical picture, ranging from mild haemolysis to life-threatening anaemia
- may be primary or secondary
what is the investigation of warm autoimmune haemolytic anaemia?
- evidence of haemolysis
- direct Coombs’ test is positive
what is the management of warm autoimmune haemolytic anaemia?
- 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.
what are clinical features of 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 intravascular 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.
what is the investigation of cold autoimmune haemolytic anaemia?
- there is evidence of haemolysis and direct Coombs’ test is positive.
- examination of a peripheral blood film at room temperature shows red cell agglutination.
what is the management of cold autoimmune haemolytic anaemia?
treat underlying condition and avoid exposure to cold
what are the two mechanisms for drug-induced haemolysis?
- in the most common 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.
what is the pathophysiology of paroxysmal nocturnal haemoglobulinuria?
- 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 haemolytic action of complement
what is the clinical presentation of paroxysmal nocturnal haemoglobulinuria?
- the clinical manifestations of this rare disease are related to abnormalities in haemopoietic function, including intravascular haemolysis, venous thrombosis and bone marrow aplasia.
- haemoglobinuria typically manifests as dark urine at night and in the morning on waking.
- progression to myelodysplasia and acute leukaemia can also occur.
what is the diagnosis of paroxysmal nocturnal haemoglobulinuria?
- 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
what is treatment of paroxysmal nocturnal haemoglobulinuria?
- treatment is supportive (e.g. with blood transfusions) and with eculizumab, a monoclonal antibody that binds to the C5 component of complement, prevents its activation and reduces haemolysis.
- BMT has been successful in selected patients.
what are examples of mechanical haemolytic anaemia?
- 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).
what is secondary polycythemia? what are presentations and treatments of it?
- secondary polycythaemia presents with similar clinical features to primary polycythaemia, although the white cell and platelet counts are usually normal and the spleen is not enlarged.
- in patients with tumours the primary disease must be treated to lower the level of erythropoietin.
- in hypoxic patients, oxygen therapy may reduce the Hb, and a small-volume phlebotomy (400 mL) may help those with severe symptoms.
- smokers should be advised to stop smoking.
what is essential thrombocythaemia?
- patients have normal Hb levels and white cell count but elevated platelet count.
- platelet size and function are abnormal, and presentation may be with bleeding or thrombosis.
what are differential diagnoses of a raised platelet count?
- reactive thrombocytosis
- autoimmune rheumatic disorders
- chronic infections
- inflammatory bowel disease
- malignancy
- haemorrhage
- surgery
- splenectomy and functional hyposplenism
- primary thrombocythaemia
- polycythaemia vera
- myelofibrosis
- myelodysplasia