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Features of megaloblastic and non megaloblastic anemia
- 1. Describe the etiology and distinguishing features of megaloblastic and non-megaloblastic macrocytic anaemia
- 2. Normal RBC •6.7–7.7 μm in size, round with smooth contours, and stain deep pink at the periphery and paler in the center. •Central pallor – approx.1/3rd the diameter of the red cell. •Size of a normal red cell - size of the nucleus of a small lymphocyte. •Normal red cells - normocytic and normochromic. 4/14/2024
- 3. What is anemia ??? 4/14/2024
- 4. Anemia Anemia is a condition in which red blood cells or their oxygen carrying capacity is insufficient to meet physiological needs which vary by age, sex, altitude , smoking and pregnancy status.
- 5. • Normal levels of hemoglobin
- 6. WHO grade of ANEMIA 4/14/2024
- 7. Classification of ANEMIA •Etiological Classification •Morphological classification 4/14/2024
- 8. Etiological classification Impaired RBC production (Decreased production) • Aplastic anemia • Myelodysplastic syndrome • Nutritional deficiency anemia - iron deficiency anemia - B12/folic acid deficiency anemia • Anemia of chronic disorder • Erythropoietin underproduction Hemorrhagic/Blood loss • Trauma • Surgery • Stomach ulcer • Heavy menstrual bleeding Hemolytic anemia(increased destruction) • Immune mediated hemolytic anemia - Transfusion reaction - infections - mechanical trauma - autoimmune disorder - drugs - malignancies • Non immune mediated hemolytic anemia - Enzyme deficiencies - Hemoglobin defects - Red cell membrane disorder
- 11. Macrocytic Anemia • Macrocytic anemia simply means anemia with MCV > 100 fl • These can be divided into megaloblastic and non- megaloblastic type 4/14/2024 Megaloblastic anemia B12 deficiency • (Pernicious anemiak Folate deficiency • (Dietary insufficiency) Non Megaloblastic anemia Alcohol Reticulocytosis •(Haemolysis) Liver disease Hypothyroidism Singh T. Atlas and text of hematology. Avichal Pub-lishing Company, New Delhi. 2010;136.
- 13. Macrocytic Anemia PERIPHERAL SMEAR: Macro ovalocytes in which central pallor is reduced Basophilic stippling Howell Jolly bodies Cabot rings Neutrophil hyper segmentation Pancytopenia
- 14. Macrocytic Anemia o Red cells are larger than the nucleus of the small lymphocyte (Size > 8.5 μm in diameter) o >3% neutrophils showing 5 or more lobes or > 1 neutrophil with 6 or more lobes. o Defect in the production of DNA causes the maturation process to be slower than normal which in turn causes the nucleus to hypersegment. o Seen in 1. Megaloblastic anemia 2. MDS 3. PATIENT ON CHEMOTHERAPY To differentiate Megaloblastic anemia from non megaloblastic anemia: Neutrophil hypersegmentation or Macro-ovalocytes
- 15. BASOPHILIC STIPPLING • Numerous small, purplish inclusions, which result from RNA and mitochondrial remnants. • Seen in • Lead toxicity • Thalassemias • Hemoglobinopathies • Macrocytic anemias
- 16. Cabot rings • Cabot rings are delicate thread-like inclusions, remnants of the nuclear membranes, in the RBC • variety of shapes and sizes. • Purplish rings, figures-of-eight, incomplete rings appearing in the center or near the periphery of erythrocytes. • Seen in • Pernicious anemia • Lead poisoning • Alcoholic jaundice • Severe anemia • Leukemia. 4/14/2024
- 17. Howell-Jolly bodies • Small, well-defined, round, densely stained inclusions; 1 μm in diameter, eccentric in location that represent DNA fragments which were once part of the nucleus of immature red cells. • Howell-Jolly bodies are seen in • Postsplenectomy or hyposplenia • Newborn • Megaloblastic anemias • Dyserythropoietic anemias • Hereditary spherocytosis. 4/14/2024
- 18. Macrocytic Anemia Bone Marrow: Megaloblasts Erythroid hyperplasia Giant metamyelocyte Band forms Megakaryocytes are enlarged 4/14/2024
- 19. Megaloblast • Abnormal red cell precursor. • Nuclear maturation lags behind cytoplasmic maturation. • Chromatin is less condensed than that of a normoblast. (sieve like ) • Nucleus is irregular • May contain Howell jolly bodies.
- 20. Erythroid Hyperplasia • It is a condition of excessive count of erythroid precursor cells in the bone marrow. • Usually a compensatory condition • Can result from 1.Increased erythropoietin production 2.Increased peripheral erythrocyte loss 4/14/2024
- 21. Giant metamyelocyte • Size: 10 to 15 μm • N:C: 1:1 • Chromatin: Indented- shaped nucleus resembling a kidney structure, patches of coarse chromatin in spots. • Cytoplasm: Pale blue to pinkish tan with moderate specific granules. • Differentiating characteristics: Nuclear indentation and condensed chromatin with no nuclei. 4/14/2024
- 24. Megaloblastic Anemia Metabolic function of vitamin B12 & folic acid Homocysteine THF Methyl B12 Methionine N-5-METHYL THF N5, 10 methylene THF dUMP dTMP DNA 4/14/2024 Methylmalonyl CoA Succinyl CoA B12 Singh T. Atlas and text of hematology. Avichal Pub-lishing Company, New Delhi. 2010;136.
- 27. Megaloblastic Anemia 4/14/2024 Singh T. Atlas and text of hematology. Avichal Pub-lishing Company, New Delhi. 2010;136.
- 28. Non- Megaloblastic Anemia Macrocytic Anemia in which RBC precursors appear normal without characteristic Nuclear and Cytoplasmic findings of Megaloblastosis. DNA synthesis is unimpaired MCV is usually 100-110fl Macrocytosis is usually mild 4/14/2024 Wintrobe MM. Wintrobe's clinical hematology. Lippincott Williams & Wilkins; 2008.
- 29. Non- Megaloblastic Anemia • Hypothyroidism • Excessive alcohol intake • Aplastic anemia • Liver disease • Myelodysplastic syndrome • Acute leukemia • Pure red cell aplasia 4/14/2024
- 30. Non- Megaloblastic Anemia 1. Macrocytosis of Alcoholism: Due to direct effect of alcohol on bone marrow and antibodies against acetaldehyde modified RBC protein MCV elevation usually slight (100-110 fl) Minimal or no anemia Macrocytes round (not oval) Neutrophil hypersegmentation absent Folate stores normal 4/14/2024
- 31. Non-Megaloblastic Anemia 2. Liver disease: Thin macrocytes: increase surface area without increase in volume due to excessive membrane lipids, especially. cholesterol, but also phospholipids. 4/14/2024 Spur cells
- 33. Diagnosis 4/14/2024 B12 Deficiency anemia Peripheral blood smear -Show large RBC’s (macro-ovalocyte) -Hypersegmented Neutrophils Bone Marrow Study - Megaloblastic changes in RBC’s precursor at various stages of differentiation . Biochemical test - Homocysteine Levels & Methylmalonic acid Levels are elevated - Schilling test Folic acid Deficiency anemia No neurological symptoms occur as methylmalonic acid levels are normal. Homocysteine level are elevated Methylmalonic acid levels are normal
- 34. Cases Case 1 • 65 year old Male • Caucasian • C/O frequent fall • Low Hb levels
- 35. Case 1 Frequent fall suggestive of neurological dysfunction VIT B12 deficiency Confirmed on P/S findings Rule out low dietary intake Pinpoint the cause of dec. absorption • Anti intrinsic factor antibody for pernicious anemia • Endoscopic/imaging studies for Chron’s disease
- 36. •50 year old , Female •Hispasian individual •History of chronic alcoholic consumption •Mouth sores •Low hb level Case 2
- 37. Case 2 Based on history of alcohol use Folate deficiency Confirmation By P/S Homocysteine levels • Methyl Malonyc acid levels
- 38. Thank you