Anemia overview document discusses red blood cell parameters, survival and production of RBCs, erythropoiesis process, classification of anemias, common causes, pathophysiology, bone marrow disorders, definitions of aplastic anemia, myelodysplastic syndromes, and acute leukemia. Diagnosis of anemia involves history, physical exam, labs including complete blood count and smears to evaluate RBC size and check for other abnormalities. Treatment focuses on supporting hematopoiesis, blood transfusions, and curing the underlying cause.

1. Anemia Overview Ruozhi Xiao The Third Hospital of Sun Yat-sen University [email_address]

2. Erythrocytes parameters RBC = red blood cells Hgb= hemoglobin Mean corpuscular volume (MCV) N: 80-100 fl RDW(Red cell Distr i bution Width) Mean corpuscular hemoglobin (MCH) N: 27-34 pg Mean corpuscular hemoglobin concentration (MCHC) N: 310 – 370 g/lRBC (31-37 g/dl)

3. Survival and Production of RBC Formed in bone marrow Life span is 120 days (+/-20 days) Cleared in spleen Reticulocytes are newly formed RBC in circulation If no new production, Hgb drops 1 gm/week

5. ERYTHROPOIESIS In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages Proerythroblast RBC * -blast is the common suffix for an immature form of a cell Early erythroblast Intermediate erythroblast Late erythroblast Reticulocyte … … … … Stem cell

6. Hematocrits Normal, Hemorrhage, IDA, Leukemia, Hemolysis, B12, P Vera Plasma White cells Red cells

7. Definitinon “ Low blood” Anemia is simply a hemoglobin level lower than the normal range for a particular age and sex of the patient. Most common hematologic disorder by far

8. The normal range for Hb and RBC Hb RBC Males ： 120 － 160g/L (4.0-5.5)x 10 12 /L Females ： 110 － 150g/L (3.5-5.0)x 10 12 /L Neonates ： 170 － 200g/L (6.0-7.0)x 10 12 /L

9. Anemia classification Based on general mechanisms morphological classification

10. Anemia morphological classification Microcytic Normocytic Macrocytic

11. morphological classification Type MCV fl MCH pg MCHC % Macrocytic anemia ＞ 100 ＞ 32 32-35 Normocytic anemia 80-100 27-32 32-35 Microcytic anemia ＜ 80 ＜ 27 ＜ 32

12. Normal Red Blood Cells - Peripheral Blood Smear

13. Normal Red Blood Cells

15. Microcytic anemia

16. Thalassemia Thalassa = the sea Defective globin synthesis Normal  1   thalassemia

17. b-Thalassemia

19. Macrocytic anemia

20. General mechanisms of anemia 1. RBC Loss without RBC destruction 2. Deficient RBC production: Marrow failure 3. Increased RBC destruction over production: Hemolysis

21. ANEMIA Causes - Cytoplasmic Protein Production Decreased hemoglobin synthesis Disorders of globin synthesis Disorders of heme synthesis Heme synthesis Decreased Iron Iron not in utilizable form Decreased heme synthesis

22. Pathophysiology Decreased RBC production Iron deficiency Folic acid deficiency Aplastic anemia Increased RBC loss or destruction sickle cell anemia blood loss infection

23. The third hospital of Sun yat-sen university :Leukemia : trauma,surgery : cancer and ulcer,menstrual periods :Renal disease : Malaria :Lead poisoning : SLE :PNH

24. Bone Marrow Disorders Aplastic anemia Myelodysplastic Syndromes Acute Leukemia

25. Aplastic Anemia Blood Bone Marrow Biopsy

26. Bone Marrow (BM) Biopsy Normal Aplastic

27. Definitions Aplastic Anemia (AA) Pancytopenia Hypocellular bone marrow Myelodysplastic Syndrome (MDS) Cytopenias with hypercellular bone marrow Acute Leukemia (AL) Malignant proliferation of immature cells

28. Aplastic Anemia: Signs and Symptoms Anemia (low Hb, Hct) fatigue, lassitude, dyspnea Thrombocytopenia (low platelets) bruises, petechiae serious bleeding Neutropenia (low neutrophils, a type of white cell) infections

29. Acquired Aplastic Anemia Drugs Chemicals Viruses Immune diseases Paroxysmal nocturnal hemoglobinuria (PNH) Pregnancy IDIOPATHIC

30. Myelodysplastic Syndromes (MDS) Clonal diseases Neoplastic Refractory anemias Potential for acute myeloid leukemia (AML)

31. Anemia Check MCV MCV < 80 Microcytic anemia MCV 80 - 100 Normocytic anemia MCV > 100 Macrocytic anemia Defective synthesis of: Heme iron deficiency anemia anemia of chronic disease sideroblastic anemia lead poisoning Globin chains thalassemias HbE Fe

32. Clinical features Mild:Mild dyspnea on exertion, palpitation Moderate: As with MILD ANEMIA, may also have excessive dyspnea Severe:Anemia:Dyspnea at rest, tachycardia with pounding pulse, weakness, dizziness, headache, insomnia

33. Diagnosis of Anemia History –Diet –Blood loss –Family history –Recent illness or immunization –History of anemia and cause

34. Diagnosis of Anemia Physical Examination – Evaluate conjunctiva and mucous membranes for paleness – Cardiovascular system for murmur – Liver – Spleen – Nodes – Look for jaundice or purpura

35. Diagnosis of Anemia Labs – Complete blood count with differential and platelets – Evaluation of smear with red cell indices – Reticulocyte count

36. Diagnosis of Anemia Other tests – Serum bilirubin, LDH, urinary hemosiderin, hgb electrophoresis, quantitative hgbA2 and F

37. Common treatment to All “Anemias” Support Hematopoietic growth factors Blood transfusions, blood substitutes Iron Cure Stem cell transplant Gene therapy

38. IRON DEFICIENCY ANEMIA

39. Terms Fe = iron TIBC = total iron binding capacity RDW = red cell distribution width

40. CASE 1 A 50 year old man comes to see you because of fatigue and a change in bowel habit. He is found to have a hemoglobin of 105 g/L (normal 120-170) and MCV of 78 fL (80-100). Peripheral blood film shows microcytes and hypochromia. He previously had a hemoglobin of 165 g/L three years ago, with a normal MCV.

41. Case 1 – Question 1 What is your approach to the history and physical examination?

42. Case 1 - Question 1 Discussion iron deficiency most likely symptoms suspicious for lower GI tract malignancy. still ask about chronic inflammatory diseases ask about melena, hematochezia, weight loss, family history of colon ca rectal exam indicated

43. CASE 1 - Question 2 What other investigations are appropriate?

44. Investigations serum ferritin 12 ug/L (30-400) iron 8 umol/L (10-28) TIBC 80 umol/L (38-76) transferrin sat. 10 % (20-55) Conclusion: Iron deficiency anemia

45. IRON DEFICIENCY ANEMIA Prevalence

46. IRON Functions as electron transporter; vital for life Must be in ferrous (Fe +2 ) state for activity Ferric (Fe +3 ) ions cannot transport electrons or O 2

47. IRON DEFICIENCY ANEMIA IRON METABOLISM ABSORPTION IN DUODENUM TRANSFERRIN TRANSPORTS IRON TO THE CELLS FERRITIN AND HEMOS I DERIN STORE IRON 10% of daily iron is absorbed

48. Iron Metabolism Heme Iron Hemoglobin and myoglobin Non-heme Iron Breast milk Cow milk All supplements

49. Iron Absorption Heme Iron Well absorbed Not dependent on Iron deficiency status Not limited by diet

50. Iron Absorption Non-heme Iron Absorption is sporadic, generally poor Improved absorption Iron deficient status Heme iron (ie red meat, fish, chicken) Vitamin C Worsened absorption Cow’s milk, cheese Cereal Tea

51. IRON Body Compartments - 75 kg man 3 mg Absorption < 1 mg/day Excretion < 1 mg/day Stores 1000mg Tissue 500 mg Red Cells 2300 mg

52. Iron deficiency anemia Causes: inadequate dietary iron intake Malabsorption: gastrectomy, chronic diarrhea, increased iron needs: pregnancy and lactation chronic occult blood loss: bleeding ulcers, GI inflammation, hemorrhoids, cancer, chronic hemoglobinuria Menstrual blood loss

53. Most body iron is present in hemoglobin in circulating red cells The macrophages of the reticuloendothelial system store iron released from hemoglobin as ferritin and hemosiderin S mall loss of iron each day in urine, faeces , skin and nails and in menstrua ting females as blood (1-2 mg daily)

54. IRON DEFICIENCY ANEMIA ETIOLOGY: CHRONIC BLEEDING MENORRHAGIA PEPTIC ULCER STOMACH CANCER ULCERATIVE COLITIS INTESTINAL CANCER HAEMORRHOIDS DECREASED IRON INTAKE INCREASED IRON REQUIRMENT (JUVENILE AGE, PREGNANCY, LACTATION)

55. IRON DEFICENCY - STAGES Prelatent reduction in iron stores without reduced serum iron levels Hb (N), MCV (N), iron absorption (  ), transferin saturation (N), serum ferritin (  ), marrow iron (  ) Latent iron stores are exhausted, but the blood hemoglobin level remains normal Hb (N), MCV (N), TIBC (  ), serum ferritin (  ), transfe r rin saturation (  ), marrow iron (absent) Iron deficiency anemia blood hemoglobin concentration falls below the lower limit of normal Hb (  ), MCV (  ), TIBC (  ), serum ferritin (  ), transfer r in saturation (  ), marrow iron (absent)

56. IRON DEFICIENCY ANEMIA GENERAL ANEMIA’S SYMPTOMS: FATIGABILITY DIZZENES S HEADACHE IRRITABILITY ROARING PALPITATION CHD, CHF

57. CHARACTERISTICS SYMPTOMS GLOSSITIS, STOMATITIS DYSPHAGIA ( Plummer-Vinson syndrome ) ATROPHIC GASTRITIS DRY, PALE SKIN SPOON SHAPED NAILS, KOILONYCHIA, BLUE SCLERAE HAIR LOSS PICA (APETITE FOR NON FOOD SUBSTANCES SUCH AS AN ICE, CLAY) SPLENOMEGALY (10%) INCREASED PLATELET COUNT

58. KOILONYCHIA

59. Smooth tongue

60. IRON DEFICIENCY ANEMIA MCV MCH MCHC N Fe TIBC TRANSFERIN SATURATION FERRITIN

61. BLOOD ROUTINE

62. BLOOD AND BONE MARROW SMEAR BLOOD: microcytosis, hipochromia, anisocytosis poikilocytosis BONE MARROW high cellularity mild to moderate erythroid hyperplasia ( 25-35%; N 16 – 18% ) polychromatic and pyknotic cytoplasm of erythroblasts is vacuolated and irregular in outline ( micronormoblastic erythropoiesis ) absence of stainable iron

63. Anemia: Lab Evaluation Normal Periperhal Smear Iron Deficiency Anemia

64. IDA blood smear

65. IDA bone marrow

66. Normal store iron(blue)

67. IDA

68. Reticulocytes up

69. Using special stains such as methylene blue or brilliant cresyl blue, reticulocytes stain with dark blue granules whereas mature erythrocytes evenly stain pale blue.

70. Management History and physical examination is sufficient to exclude serious disease (e.g pregnant or lactating women, adolescents) - CURE ANEMIA

71. Management History and/or physical examination is insufficient (e.g old men, postmenopausal women) - FIND ETIOLOGY OF ANEMIA AND CURE (CAUSAL TREATMENT) Benzidine test Gastroscopy Colonoscopy Gynaecological examination

72. IRON DEFICIENCY ANEMIA CURE ORAL 3 00 mg of iron daily after meal How long? 3-6 months to restore iron reserve Absorption is enhanced: vit C, meat, orange juice, fish is inhibited: tea, milk

73. IRON DEFICIENCY ANEMIA CURE PARENTERAL IRON SUBSTITUTION Bad oral iron tolerance (nausea, diarrhoea) Negative oral iron absorption test Necessity of quick management (CHD, CHF)

74. Remember: Iron deficiency anemia is a manifestation of an underlying process. Look for and treat the cause of the iron deficiency.

75. Look for the cause colonoscopy reveals colon carcinoma which is subsequently resected.

76. Iron Deficiency anemia Diagnostics: Iron levels Total iron-binding capacity (TIBC) Serum Ferritin Medications: Iron supplements, oral or parenteral Vit. C

77. The End