Microcytic anemia

Microcytic hypochromic anemia- iron deficiency, anemia of chronic disease, thalassemia minor, sideroblastic anemia

1. MICROCYTIC ANEMIA Presented by- Dr. Monika Nema Dr. Monika Nema

2. What is Anemia Anemia is the collection of signs and symptoms of reduced oxygen delivery to tissues as a result of a reduction in the number of red cells and/or reduction in blood concentration of hemoglobin below the level that is expected for healthy person of same age and sex. Dr. Monika Nema

3. The world health organization (WHO) has defined anemia as Hb <13.0 g/dl for men and <12g/dl for women. Dr. Monika Nema

4. Hb ( g/dl ) Ht(%) MCV (fl) Adult men 13-17 39-49 80-100 Adult women 12-15 33-43 80-100 Children 6-12 yr 11.5-12.5 37-46 77-95 6m-6yr 11-14 36-42 74-87 2m-6m 9.5-14 32-42 76-84 Dr. Monika Nema

5. Anemia Most common hematologic disorder by far It is a clinical sign of disease It is not a single disease by itself. Dr. Monika Nema

6. Erythrocytes parameters Dr. Monika Nema

7. Mean corpuscular volume Average volume of a single red cell. Normal : 83-101 femtolitre Calculated as MCV= Packed cell volume x 10 Red cell count Dr. Monika Nema

8. Mean corpuscular haemoglobin Average amount of haemoglobin in each red cells. Normal: 27-32 picogram . MCH= Hemoglobin concentration x 10 Red cell count Dr. Monika Nema

9. MEAN CORPUSCULAR HAEMOGLOBIN CONCENTRATION Represents the average concentration of haemoglobin in a given volume of packed cells. Normal : 31.5-34.5 g/dl. MCHC= Hemoglobin concentration x 100 Packed cell volume Dr. Monika Nema

10. Red cell distribution width It is a measure of degree of variation in red cell size( anisocytosis ) in a blood sample. Normal : As coefficient of variation(CV)- 11.6-14 % As Standard deviation(SD) – 39-46% Dr. Monika Nema

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12. Morphologic Classification of ANEMIA Normocytic Normochromic Microcytic Hypochromic Macrocytic Dr. Monika Nema

13. Microcytic anemia Dr. Monika Nema

14. case A patient presented with fatigue, shortness of breath, weakness, irritability, reduced work concentration to the physician. Doctor examined and found pallor. He simply ordered a complete blood count. Dr. Monika Nema

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16. microcytic anemia When the average cell size (MCV) is reduced, the anemia is classified as MICROCYTIC ANEMIA. Usually associated with hypochromia It is very common in all age groups. Dr. Monika Nema

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18. Microcytic hypochromic picture Dr. Monika Nema

19. Pathogenic classification of microcytic anemia Disorders of iron metabolism - Iron deficiency anemia. - Anemia of chronic disorder. Disorder of globin synthesis - Alpha and Beta Thalassemia . Dr. Monika Nema

20. Pathogenic classification of microcytic anemia Sideroblastic anemia - Hereditary. - Acquired. - Reversible Acquired. Lead Intoxication. Dr. Monika Nema

21. Clinical features Dr. Monika Nema

22. Shortness of breath Palpitation Decreased work or exercise tolerance Fatigue Weakness Dr. Monika Nema

23. Iron deficiency anemia Pica ( Abnormal eating pattern ) is striking symptom of iron deficiency anemia. Dr. Monika Nema

24. Iron deficiency anemia Iron deficiency usually arises from chronic blood loss. The major cause in younger women is menstruation. In non menstruating women and in men, the most common source is gastrointestinal hemorrhage. (esophageal varices,hiatus hernia, peptic ulcer,gastritis,neoplasm ,hook worm infestation) Dr. Monika Nema

25. CAUSES OF IRON DEFICIENCY ANEMIA Inadequate dietary intake of iron Defective absorption of iron ( Achlorhydriya , Gastric surgery, Celiac disease, Duodenal bypass, Drugs, Tannins, Phytate , Bran) Dr. Monika Nema

26. Increased requirements of iron (Pregnancy, Infancy, Lactation) Inadequate presentation to erythroid precursors ( Atransferrinemia , Atransferrin receptor antibodies) Abnormal iron balance ( Aceruloplasminemia , Autosomal dominent hemochromatosis due to mutation in ferroportin ) Dr. Monika Nema

27. Thalassemia Is an inherited autosomal recessive blood disease which results in reduced synthesis or no synthesis of one of the globin chains that make up hemoglobin causing the formation of abnormal hemoglobin molecules leading to anemia. Thalassemia is a quantitative problem. Dr. Monika Nema

28. Thalassemia minor patients are usually asymptomatic. Diagnosis is made through evaluation of positive family history. Dr. Monika Nema

29. Sideroblastic anemia These are group of disorders of varying aetiology in which marrow shows marked dyserythropoiesis & intra mitochondrial accumulation of Fe in erythroid precursors Dr. Monika Nema

30. In sideroblastic anemia, majority of patient exhibits manifestations of iron overload. Abnormal glucose tolerance, cardiac arrhythmia and congestive heart failure can occur. Dr. Monika Nema

31. In case of Lead poisoning, There can be occupational history of inhaling fumes in industry. Ingestion of lead based paint chips by children. Ingestion of contaminated herbs and food supplements. Gasoline sniffing in addicted person. Dr. Monika Nema

32. Causes of anemia of chronic disease Chronic inflammation Rheumatoid arthritis systemic lupus erythematosis Crohn’s disease B. Chronic infection Tuberculosis Urinary tract disease HIV infection Bacterial endocarditis pneumonia C. Neoplasm Carcinoma Lymphoma Myeloma Dr. Monika Nema

33. Pathogenesis of Anemia of chronic disease Anemia is related to decrease in release of iron from macrophage to plasma Reduced RBC lifespan Inadequate erythropoietin response to anemia, caused by effects of cytokine such IL-1, TNF on erythropoiesis Hepcidin released by the liver in response to inflammation. Hepcidin functions to regulate (inhibit) iron transport across the gut mucosa, thereby preventing excess iron absorption and maintaining normal iron levels within the body. Hepcidin also inhibits transport of iron out of macrophages (where iron is stored) Dr. Monika Nema

34. The clinical manifestation vary widely in anemia of chronic disease because of its association with so many diseases. Usually, the signs and symptoms of the underlying disorder overshadow those of the anemia. Dr. Monika Nema

35. pallor In the hands, the skin of the palms first becomes pale, but the creases may retain their usual pink color until the Hb concentration is less than 7 g/dl. Is a sign of anemia. The pallor associated with anemia is best detected in the mucus membrane of mouth, the conjunctiva, lips and the nail beds Dr. Monika Nema

36. Lesions associated with iron deficiency anemia Site Findings Nails Flattening, Koilonychia Tongue Soreness, Mild papillary atrophy, Absence of filiform papillae Mouth Angular stomatitis Hypopharynx Dysphagia,Esophageal varices Stomach Achlorhydria,Gastritis Koilonychia Dr. Monika Nema

37. Lead posioning Gums in lead poisoning. Lead lines are shown in gums of this patient suffering from lead poisoning Dr. Monika Nema

38. Laboratory findings Dr. Monika Nema

39. Disorder of iron metabolism Most microcytic anemia are due to deficient hemoglobin synthesis often associated with iron deficiency or impaired iron use. Dr. Monika Nema

40. Iron deficiency anemia Erythrocytes : If symptoms of anemia are the presenting complain, the blood hemoglobin is usually 8 g/dl or lower. MCV – decreased. ( Microcytic ) MCH- decreased. ( Hypochromic ) Anisocytosis - Important early sign . Leading to raised Red Cell Distribution Width. Few pencil cells, few target cells can be seen. Dr. Monika Nema

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42. Iron deficiency anemia Leukocytes: Usually normal in number. Mild graulocytopenia is seen in long standing cases. Recent large volume hemorrhage leads to Neutrophilic Leukocytosis . Due to parasitic infestation, Eosinophilia can be seen. Thrombocytes : Thrombocytosis is usually seen. Dr. Monika Nema

43. Peripheral smear in iron deficiency anemia Dr. Monika Nema

44. The normal film shows little variation in red cell size The iron deficient cells shows variations in size ( anisocytosis ) and shape ( poikilocytosis ), as well as microcytosis (low average cell size) and hypochromia (increased central pallor). Dr. Monika Nema

45. Anemia of chronic disease Usually normocytic normochromic anemia is seen. Hypochromia is more common than microcytosis . Microcytosis in anemia of chronic disease is usually not as striking as that commonly associated with iron deficiency anemia. Dr. Monika Nema

46. In iron deficiency anemia, hypochromia follows microcytosis . Whereas in anemia of chronic disease, hypochromia preceeds microcytosis . Dr. Monika Nema

47. Normocytic picture Microcytic picture Dr. Monika Nema

48. Certain normal serum levels of iron metabolism Dr. Monika Nema

49. Serum iron It is a measure of amount of iron bound to transferrin . Shows diurnal variation Highest in morning and lowest in evening. Influenced by recent ingestion and absorption of iron medication. Normal value : 0.6-1.7 microgram/L. Dr. Monika Nema

50. Transferrin The principal source of iron for hemoglobin production is that carried by transferrin , the iron transport protein in plasma. When transferrin saturation with iron is less than 16%, RBC production rate decreases and hypochromic,microcytic cells are manufactured. This state is known as iron deficient erythropoiesis . Normal transferrin saturation is 16-50%. Dr. Monika Nema

51. Total iron binding capacity It is indirect measurement of transferrin in terms of amount of iron it will bind. Shows slight fluctuation. Normal value : 2.5-4.0 microgram/L. Dr. Monika Nema

52. TRANSFERRIN rECEPTOR Disulphide linked transmembrane protein that facilitates entry of transferrin bound iron into cells. Dr. Monika Nema

53. Serum ferritin Ferritin is chiefly intracellular iron storage protein. Serum ferritin is glycosylated and contains little or no iron. In most circumstances, Serum ferritin is proportional to total body iron stores. Not influenced by recent iron therapy. Normal : Male – 15-300 microgram/L. Female – 15-200 microgram/L. Dr. Monika Nema

54. Serum ferritin Ferritin levels are the single best serum measure of storage iron. Serum ferritin level in patient with anemia of chronic diseases may increase dispropotinately relative to increase in iron stores, probably because ferritin is an Acute phase reactant. This phenomenon complicates diagnosis of Iron deficiency anemia when it co-exists with inflammatory disease. Dr. Monika Nema

55. Serum level that differentiate anemia of chronic disease from iron deficiency anemia Dr. Monika Nema

56. Total iron binding capacity – Increased in iron deficiency anemia Decreased in anemia of chronic disease. Erythrocyte sedimentation rate is found to be elevated in anemia of chronic disease owing to its inflammatory etiology. Dr. Monika Nema

57. BONE MARROW FEATUREs of iron deficiency anemia Cellularity – increased Erythroid hyperplasia Micronormoblastic reaction Normoblast are smaller Late micronormoblast demonstrates persistent basophilia and fraying of cytoplasmic borders indicating lack of complete hemoglobinization Myelopoiesis – Normal Megakaryopoiesis – Normal Depleted bone marrow iron Dr. Monika Nema

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59. BONE MARROW FEATUREs of anemia of chronic disease Bone marrow aspirate demonstrating increased iron staining in a fragment representing increased marrow iron stores. . This finding is present in a patient with anemia of chronic disease. Normal iron staining in histiocytes is shown for comparison Dr. Monika Nema

60. Criteria for grading iron stores Grade Criteria No iron granules observed 1+ Small granules in reticulum cells, seen only in oil immersion lens 2+ Few small granules seen with low power lens 3+ Numerous small granules in all marrow particles 4+ Large granules in small clumps 5+ Dense, large clumps of granules 6+ Very large granules, obscuring marrow details Normal Marrow =1+ To 3+ Dr. Monika Nema

61. Thalassemia minor Red cell count is increased. MCV –decreased. MCH- decreased. MCHC- normal or slightly decreased. Reticulocytes are generally increased to twice the normal number and have been found to correlate with hemoglobin level. Dr. Monika Nema

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63. Peripheral picture of thalassemia minor Target cells Dr. Monika Nema

64. Peripheral picture of thalassemia minor Basophilic stippling in thalassemia . Dr. Monika Nema

65. Thalassemia minor V/s iron deficency anemia Dr. Monika Nema

66. Thalassemia minor V/s iron deficency anemia Findings Thalassemia minor Iron deficiency anemia Anisocytosis Mild or absent Early and prominent finding Microcytosis More severe Less severe Dr. Monika Nema

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68. Mentzer index Mentzer index= Mean cell volume Red cell count Value greater than 14 is found in iron deficiency anemia whereas value less than 12 is seen in thalassemia trait disorder. Value between 12-14 is considered indeterminate. Dr. Monika Nema

69. Kerman index 1 Calculated as MCV x MCH Red cell count >371: normal 321-370: iron def.=> trial of iron for 1 mo. 251-320: Mixed iron def. & minor thalassemia => trial of iron & folate then check CBC & Hb elect <250 : Minor thalassemia =>check Hb elect. Sensitivity =99% , Specificity=86% Dr. Monika Nema

70. Kerman index 2 Calculated as MCV x MCH Red cell count x MCHC >13: Normal 10.5-13: Iron deficiency 8-10.5: Mixed iron def & minor thalassemia . <8 : Minor thalassemia Note : Sensitivity=99% , Specificity=93% Dr. Monika Nema

71. Special test HbF E lectrophoresis High performance liquid chromatography DNA analysis Dr. Monika Nema

72. Hb A 2 ranges 3.5 to 7.0 % Hb F ranges 1 – 3 % Dr. Monika Nema

73. Bone marrow features of thalassemia Hypercellular Erythroid hyperplasia M:E ratio 1:5 Dyserythropoisis Myelopoisis and megakaryopoisis are normal Bone marrow iron increased Dr. Monika Nema

74. Bone marrow features of thalassemia Top and bottom panels show bone marrow aspirate and biopsy, respectively, from a case of thalassemia trait. The bone marrow has increased numbers of erythroid precursors (a low myeloid to erythroid ratio) related to the increased peripheral RBC destruction in this disease. Dr. Monika Nema

75. sideroblastic anemia Peripheral smear: microcytic hypochromic , anisopoiklocytosis ,few cell show basophilic stippling,WBC and platelet normal. Serum iron and percent transferrin saturation increased Bone marrow : hypercellular,normoblastic or micronormoblastic reaction with vacuolation in cytoplasm, sideroblast , megakaryopoisis and normal myelopoisis . Dr. Monika Nema

76. Sideroblastic anemia. Normocytic cells are present, along with a minor population of microcytic , hypochromic erythrocytes possessing a thin rim of cytoplasm. Occasional teardrop cells are visible. Dr. Monika Nema

77. Ring sideroblast Dr. Monika Nema

78. In Sideroblastic anemia. Numerous ringed sideroblasts are seen in this marrow aspirate smear stained for iron. They are normoblasts with ≥10 iron-containing granules in the cytoplasm encircling at least one-third of the nucleus. Dr. Monika Nema

79. Lead posioning Peripheral blood film demonstrating coarse basophilic stippling. Normocytic or microcytic anemia may be present. Dr. Monika Nema

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82. THANK YOU PRESENTED BY :- DR.MONIKA NEMA Dr. Monika Nema