PATH 22 – Haemolytic Anaemia Flashcards
What are the causes of anaemia?
Failure to make red cells: Marrow problem
Lack of haematinics: iron, B12, Folate eg dietary deficiency, malabsorption, loss
Increased loss of red blood cells e.g. bleeding
Increased destruction of red cells: Haemolysis
Chronic Disease
Why would there be failure of marrow to make red cells?
Marrow hypoplasia/aplasia e.g. immune mediated
Marrow replacement
What is marrow replacement?
Any replacement of the marrow by fibrous tissue or metastases or bone marrow malignancy e.g. leukaemia can cause reduction in any or all of cells
Primary marrow failure e.g. autoimmune
e.g. to drugs or infection can do the same
How does cell respond to cell death or tumour infiltration?
Metastases Chemotherapy Radiotherapy Other drugs Idiopathic e.g. Primary Myelofibrosis
Briefly describe Haemolytic Anaemia Congenital and Acquired
Anaemia due to excess breakdown of RBCs with marrow compensation
Lysis is cell breakdown
Hemolysis breakdown of RBC’s (increased LDH/increased bilirubin)
Destruction of cells occurs in circulation or spleen
But marrow keeps on working with an elevated reticulocyte count
How does immune system cause acquired anaemia?
Immune
Autoimmune self antigens causing an immune destruction of rbc
Warm (IgG)
Cold (IgM)
What might cause antibody production against RBC?
Alloimmune non self causing immune destruction of RBC
Haemolytic transfusion reactions
Haemolytic disease of the new born
Post BMT rejection of graft
Drug associated (Dapsone)
What causes autoimmune haemolytic anaemia
May occur without obvious trigger Or with a trigger With lymphoma With infection (Mycoplasma) With other autoimmune disease e.g. SLE
Describe how to test for Immune Haemolysis Direct Antiglobulin Test – e.g. Coomb’s test
Wash red cells Add anti IgM anti IgG Look for agglutination (clumping) IgG(warm)/IgM (cold) antibody binds to red cell Red cell membrane phagocytosed
What causes non immune - acquired anaemia?
1.Red cell fragmentation syndromes due to;
>Eclampsia
>Sepsis
>Disseminated Intravascular coagulation (excess thrombi and bleeding
- Mechanical
Heart valve – prosthetic
What causes Congenital haemolytic anaemia?
> Membrane abnormalities
Enzyme abnormalities
Haemoglobin abnormalities
State the like cause of Red Cell Membrane Abnormalities
> Hereditary Spherocytosis Hereditary Elliptocytosis
Defect in a structural protein of RBC membrane e.g.: Spectrin)
Spherocytes have reduced deformability and get “stuck” in splenic microcirculation
Prematurely phagocytosed
What are the effects of Red Cell Metabolism Enzyme Defects
Glu 6 phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
RBC’s more susceptible to damage by oxidant compounds
What results from Haemoglobin defects?
> Abnormal genetic code in haemoglobin
Sickle cell disease mutation-Sickle cell disease mutation (valine for glutamic acid) causing increased HbS with rbc aggregation at low oxygen tensions
Thalassaemia major and minor
Globin chains are normal but rate of synthesis is reduced
Xss accumulation of abnormal chain leads to structural defects
Briefly describe Sickle cell anaemia
Sickle cell anaemia: coinheritance of HBS and another abnormal β chain variant
Sickle cell trait: inheritance of one gene encoding for HBS
Autosomal recessive genetic abnormality
Affects mainly Afro-Caribbean population in UK
45% gene carriers in some parts of Africa
Offers some resistance to malaria
Also in some parts of Mediterranean and Asia
Write down the pathogenesis of Sickle cell disease.
Chronic haemolytic anaemia
HbS in deoxygenated state (50X less soluble than HbA)
Insoluble chains crystallise in the red cells with distortion of membrane, cell becomes crescent shaped
Sickle RBC last only 10-20days
Deformed cells more rigid and cannot pass microcirculation
Causes vascular occlusion
Structural change and Ý bld viscosity > venous stasis > local obstruction > tissue hypoxia > more sickling > tissue infarction
