Features of megaloblastic and non megaloblastic anemia

Macrocytic anemia

1. Describe the e tiology and distinguishing features of megaloblastic and non-megaloblastic macrocytic anaemia

2. Normal RBC •6.7–7.7 μ m 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. 3/26/2024

3. What is anemia ??? 3/26/2024

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 3/26/2024

7. Classification of ANEMIA Etiological Classification Morphological classification 3/26/2024

8. Etiological classification

9. 3/26/2024 Morphological classification

10. Macrocytic Anemia 3/26/2024

11. Macrocytic Anemia Macrocytic anemia simply means anemia with MCV > 100 fl These can be divided into megaloblastic and non-megaloblastic type 3/26/2024 Singh T. Atlas and text of hematology . Avichal Pub-lishing Company, New Delhi. 2010;136.

12. Macrocytic Anemia 3/26/2024

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 Red cells are larger than the nucleus of the small lymphocyte (Size > 8.5 μ m in diameter) >3% neutrophils showing 5 or more lobes or > 1 neutrophil with 6 or more lobes. Defect in the production of DNA causes the maturation process to be slower than normal which in turn causes the nucleus to hypersegment . Seen in Megaloblastic anemia MDS 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. 3/26/2024

17. Howell-Jolly bodies Small, well-defined, round, densely stained inclusions; 1 μ m 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. 3/26/2024

18. Macrocytic Anemia Bone Marrow: Megaloblasts Erythroid hyperplasia Giant metamyelocyte Band forms Megakaryocytes are enlarged 3/26/2024

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 Increased erythropoietin production Increased peripheral erythrocyte loss 3/26/2024

21. Giant metamyelocyte Size: 10 to 15 μ m 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. 3/26/2024

22. Megaloblastic Anemia Causes

23. Megaloblastic Anemia Causes Continued…

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 3/26/2024 Methylmalonyl CoA Succinyl CoA B12 Singh T. Atlas and text of hematology . Avichal Pub-lishing Company, New Delhi. 2010;136.

25. Megaloblastic Anemia Pathophysiology 3/26/2024

26. Megaloblastic Anemia Pathophysiology 3/26/2024

27. Megaloblastic Anemia 3/26/2024 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 Megaloblastosi s. DNA synthesis is unimpaired MCV is usually 100-110fl Macrocytosis is usually mild 3/26/2024 MILD 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 3/26/2024 H E A L M A P

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 3/26/2024

31. Non-Megaloblastic Anemia 2. Liv er disease: Thin macrocytes : increase surface area without increase in volume due to excessive membrane lipids, especially. cholesterol , but also phospholipids. 3/26/2024 Spur cells

32. Macrocytic anemia

33. Diagnosis 3/26/2024 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

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