Normochromic normocytic anaemia


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Classification of Anaemia

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Normochromic normocytic anaemia

  2. 2. Chapter outline• Membrane defects: Hereditary spherocytosis• Metabolic defect: pyruvate kinase deficiency, G6PD deficiency• Haemoglobinopathies: sickle cell disease• Extrinsic abnormalities: antibody mediated transfusion reaction• Mechanical destruction: MAHA, infections
  3. 3. • Underlying causes:1. Loss of RBC:Haemorrhage2. Increased destruction of RBC3. Reduced erythropoieisis4. Reduced RBC’s survivalHaemolytic anaemia can be classified into:1. Congenital and acquired2. Intrinsic or extrinsic3. Intravascular or extravascular haemolysis
  4. 4. Morphologic classification of Anaemia – MCV based N or h RETIC Normocytic - MCV 80-100 fl Bone marrow Acellular Hypercellular h RETIC Normocellular Haemolytic anaemia Intrinsic Extrinsic PNH Membrane Chemical & Mechanical - Antibody Infection MAHA Physical Enzyme mediated damage Haeme/globin
  5. 5. Anaemia - Diagnostic Overview Clinical Symptoms Haemolysis Bilirubin hh Haptoglobin i Review Blood Film other biochem tests Morphology None PNH Spherocytes Variable findings *DAT Positive *Blister cells Sickle cells Immune mediated Stomatocytes Oxidative haemolysis Elliptocytes G6PD *DAT Negative Target cells *Fragments Hereditary Spherocytosis, Burns, C. perfringens Spur cells MAHA septicaemiaSource; modified from AH Turner, 2004 Burr cells Malaria
  6. 6. Hereditary Spherocytosis• Characterized by numerous spherocytes in blood film• Common in Northern European but can be found all over the world• Due to deficiency of RBC membrane structural proteins leading to loss of membrane surface are----- causing the RBCs to become spherocytes
  7. 7. Pathophysiology• Defect in membrane skeletal proteins that connect the membrane skeleton to the lipid bilayer ( spectrin, ankyrin, protein 4.2, band 3)• Cause RBCs progressively to lose unsupported lipid membrane because of the local disconnection• RCs become rigid and their survival in the spleen decrease
  8. 8. Clinical Features• Symptoms of anaemia• Splenomegaly• Jaundice• Megaloblastic crisis – folic acid deficiency due to increase need
  9. 9. Lab Findings• FBE- hallmark is d increase spherocytes• Hb normal, unless in crisis, MCV, MCH normal• Bone marrow- erythroid hyperplasia• Biochemistry – increased unconjugated bilirubin, fecal urobilinogen and decreased haptoglobin• DAT test- negative• Osmotic frafility test – curve shift to left• Spectrin immunoassay• Family history and genetic studies
  10. 10. Treatment & differential diagnosis• Splenectomy – post splenectomy cause the appearance of target cells, howell jolly bodies, pappenheimer bodies• Differential diagnosis – other causes of spherocytes must be ruled out AIHA, PNH,sepsis, pyropoikilocytosis
  11. 11. Metabolic defect: G6PD Deficiency• The gene for G6PD is located on X- chromosome & show a characteristic X-linked pattern• Affect more males than females• G6PD fx – maintain gluthathione (GSSG) in reduced state (GSH) to protect RBC from oxidative stress
  12. 12. RBC Membrane damageOxidant Hb Heinz bodies GSH GSSG NADP NADPH G-6P 6PG G6PD
  13. 13. Clinical Features• G6PD deficiency is usually asymptomatic but: 1.Acute haemolytic anaemia in response to oxidative stress such as drugs, fava beans, infections, etc. 2.Neonatal jaundice 3.Congenital non-spherocytic haemolytic anaemia
  14. 14. Lab Findings• FBE – depends on severity – normochromic normocytic, marked anisocytosis, poikilocytosis with bite cells and blister cells• Biochemical - haptoglobin severely , unconjugated bilirubin and plasma Hb• G6PD screening test – G6PD fluoresence spot test, G6PD enzyme detection kit, PCR analysis of mutations.
  15. 15. Differential Diagnosis• Drug induced HA• Other enzymopathies eg Pyruvate kinase deficiency• Haemoglobinopathies due to oxidative stress
  16. 16. Haem defects: Sickle Cell Disease• Hb S is defined by structural formula α2β2Glu-val which indictaes that on the B chain at 6th position, glutamic acid is replaced by valine• resulting in a structural change in RBC shape relates to the amount of O2 bound to the Hb molecules
  17. 17. Pathophysiology• When HbS is fully oxygenated it remains soluble in the erythrocyte similar to Hb A, maintaining its normal shape• On deoxygenation, Hb S becomes less soluble and causing sickling• The blood becomes more viscous when sickle cells are created. Results in reduced blood flow which prolongs the exposure of HbS containing erythrocytes to a hypoxic environment which further promotes sickling,• The end result is occlusion of capillaries and arterioles by sickled RBCs and infarction of surrounding tissues
  18. 18. Clinical Features of SCD• Hallmark feature is vaso occlusive• Gradual loss of splenic fx• Splenic sequestrationLaboratory diagnosis of SCD •Peripheral blood smear – poikilocytosis &anisocytosis, sickle cells, target cells, nRBCs, spherocytes, basohilic stippling, Howell- jolly bodies •Moderate leukocytosis & neutrophilia •thrombocytosis
  19. 19. Lab Diagnosis (Cont)• BM- erythroid hyperplasia• Elevated Indirect & direct bilirubin• Solubility & sickling test• Hb ElectrophoresisTREATMENT 1. BM transplantation 2. Transfusion 3. Hydroxyurea therapy
  20. 20. Microangiopathic Haemolytic Anaemia (MAHA)• Due to mechanical destruction• It is a group of clinical disorders characterized by RBC fragmentation in the circulation, resulting from IV haemolysis• The fragmentation occurs as RBCs passed through fibrin deposits inside the lumen of arterioles & capillaries or through damaged epithelium & vessel walls• RBCs being forced through a fibrin clot, attaching to fibrin, folding around the strands & fragmenting by the force of the flowing blood
  21. 21. • Disorders include 1) Thrombocytic thrombocytopenic purpurea (TTP) 2) Haemolyric uraemic syndrome (HUS) 3) Disseminated intravascular coagulation (DIC) 4) Haemolysis Elevated Liver enzymes & Low Platelet (HELLP)