1. Anemia Kristine Krafts, M.D.

2. Background facts about blood Anemia: general information Anemia: specific types Anemia Outline

3. Background facts about blood Anemia Outline

4. Normal blood cells

6. Complete Blood Count (CBC) RBC Hemoglobin Hematocrit

7. MCVMCHC microcyticnormocyticmacrocytic normochromichypochromic Complete Blood Count (CBC)

8. Size variation Additional Red Blood Cell Properties Shape anisocytosispoikilocytosis

9. Normal red blood cells

10. Background facts about blood Anemia: general information Anemia Outline

11. An (without) -emia (blood): a reduction below normal in hemoglobin or red blood cell number.

12. Symptoms of Anemia Pale skin, mucous membranes Jaundice (if hemolytic) Tachycardia Breathlessness Dizziness Fatigue

13. Background facts about blood Anemia: general information Anemia: specific types Anemia Outline

14. Lose blood Destroy too much blood Extracorpuscular reasons Intracorpuscular reasons Make too little blood Too few building blocks Too few erythroblasts Not enough room Three Ways to Get Anemic

15. Lose blood Three Ways to Get Anemic

16. Anemia of Blood Loss Cause: traumatic, acute blood loss At first, hemoglobin is normal! After 2-3 days, see reticulocytes Chronic blood loss is different (it causes iron deficiency anemia). Things you must know

17. Reticulocytes

18. Lose blood Destroy too much blood Extracorpuscular reasons Intracorpuscular reasons Three Ways to Get Anemic

19. Intracorpuscular vs. extracorpuscular Chronic vs. acute Signs of destruction: ↑ bilirubin, ↑ LDH, ↓ haptoglobin Signs of production: ↑ reticulocytes, nucleated red cells in blood Hemolytic Anemias

20. Reticulocytes (supravital stain)

21. Lose blood Destroy too much blood Extracorpuscular reasons Three Ways to Get Anemic

22. Microangiopathic Hemolytic Anemia Physical trauma to red cells Schistocytes Find out why! Things You Must Know

23. Red cells snagged on fibrin strand

24. Schistocytes

25. Triangulocyte

26. Artificial heart valve Malignancy Obstetric complications Sepsis Trauma Causes of MAHA

27. Warm AIHA IgG Spleen Spherocytes Cold AIHA IgM, complement Intravascular hemolysis Agglutination Autoimmune Hemolytic Anemia Things You Must Know

28. Warm AIHA

31. Cold AIHA

33. patient red cells+AHG=agglutination Direct antiglobulin test (DAT)

34. Lose blood Destroy too much blood Extracorpuscular reasons Intracorpuscular reasons Three Ways to Get Anemic

35. Hemoglobinopathy (qualitative defect in hemoglobin) Single amino acid substitution in beta chain of hemoglobin Can be heterozygous or homozygous Sickle cells are nasty: Fragile (burst easily) Get stuck in vessels Sickle Cell Anemia Things You Must Know

36. Hemoglobin

37. Point mutation in  chain gene abnormal  chains (substitution of valine for glutamate) Hgb S Aggregates and polymerizes on deoxygenation Red cell becomes sickle shaped Sickles clog up vessels… …plus, they are fragile Nasty!

38. Sickle cell anemia

40. Sickle cell anemia: foot lesion

41. Sickle cell anemia: spleen

42. Clinical Findings in Sickle Cell Anemia Blacks (8% are heterozygous) Severity of disease is variable Chronic hemolysis, vaso-occlusive disease, and  infections (autosplenectomy) Treatment: prevent triggers, vaccinate, transfuse

43. Thalassemia Quantitative defect in hemoglobin Can’t make enough α or β chains Variable disease severity Hypochromic, microcytic anemia with increased RBC and target cells Things You Must Know

44. Hemoglobin chain development birth Hgb F = α 2 γ 2 Hgb A 2 = α 2 δ 2 Hgb A = α 2 β 2 α δ β γ

45. Thalassemia

46. Thalassemia: Medullary expansion

47. Hereditary Spherocytosis Tons of spherocytes Spectrin defect Splenectomy is curative Things You Must Know

48. z

49. Hereditary spherocytosis

50. Splenomegaly in hereditary spherocytosis

51. Glucose-6-Phosphate Dehydrogenase Deficiency  G6PD →  peroxides → cell lysis Oxidant exposure Bite cells (removal of Heinz bodies) Self-limiting Things You Must Know

52. Some patients asymptomatic Others have episodic hemolysis Triggers: broad beans (favism), drugs (antibiotics, aspirin) Spontaneous resolution Clinical Findings in G6PD Deficiency

53. Child with G6PD deficiency: jaundiced sclera

55. They can’t reduce nasties Nasties attack hemoglobin bonds Heme breaks away from globin Globin denatures, sticks to red cell membrane (“Heinz body”) Spleen bites out Heinz bodies Why Do G6PD-Deficient Red Cells Die?

56. G6PD deficiency: Heinz bodies

57. G6PD deficiency: bite cells

58. Lose blood Destroy too much blood Extracorpuscular reasons Intracorpuscular reasons Make too little blood Too few building blocks Three Ways to Get Anemic

59. Iron-Deficiency Anemia Things You Must Know Most important cause: GI bleeding Microcytic, hypochromic anemia Must find out why patient is iron deficient!

60. Hemoglobin

61. Iron-deficiency anemia

62. Atrophic glossitis in iron-deficiency anemia

63. Koilonychia in iron-deficiency anemia

64. Decreased iron intake bad diet bad absorption Increased iron loss GI bleed menses hemorrhage Increased iron requirement pregnancy Causes of Iron Deficiency

65. Anemia of Chronic Disease Infections, inflammation, malignancy Iron metabolism disturbed Normochromic, normocytic anemia Anemia usually mild Things You Must Know

66. Megaloblastic Anemia Things You Must Know Defective DNA synthesis Nuclear/cytoplasmic asynchrony  B 12 /folate Macrocytic anemia with oval macrocytes and hypersegmented neutrophils

67. FH 4 methylene FH 4 FH 2 methyl FH 4 dUMP dTMP DNA B 12 Need B 12 to make DNA!

68. retarded DNA synthesis unimpaired RNA synthesis BIG cells! immature nucleus mature cytoplasm Megaloblastic Anemia

69. Megaloblastic anemia

71. Atrophic glossitis in megaloblastic anemia

72. homocysteine  homocysteine endothelial damage atherosclerosis thrombosis What else is B 12 good for? methionine  methionine myelin damage subacute combined degeneration

73. Lose blood Destroy too much blood Extracorpuscular reasons Intracorpuscular reasons Make too little blood Too few building blocks Too few erythroblasts Three Ways to Get Anemic

74. Aplastic Anemia Pancytopenia Empty marrow Most are idiopathic Things You Must Know

75. Blood smear in aplastic anemia

76. Empty bone marrow in aplastic anemia

78. Idiopathic Drugs Viruses Pregnancy Fanconi anemia Causes of Aplastic Anemia

79. Lose blood Destroy too much blood Extracorpuscular reasons Intracorpuscular reasons Make too little blood Too few building blocks Too few erythroblasts Not enough room Three Ways to Get Anemic

80. Bone marrow full of fibrosis