1. ANEMIA Hematology Department,Huashan Hospital,Fudan University,Shanghai XieYan-Hui

2. DIAGNOSIS AND CLASSIFICATIONAnemia is an absolute decrease in hematocrit, hemoglobin concentration, or the RBC count. Anemia is not a diagnosis, but a sign of underlying disease..

3. Hemoglobin(Hb): male(adult)<120g/L female(adult)<110g/L female(gestation)<100g/L Red cell count male<4.5x1012 /L female<4.0x1012 /L Hemocrit(HCT) male<0.42 female<0.37 female(gestation)<0.30

4. Determination of the cause:A. History1. Drug administration.2. Exposure to toxic chemicals 3. Family occurrence.4. Recent transfusions5.menstruation(woman)6.ingestion(child)7.chronic disease8. Age at onset.

5. B. Physical findings and complaintsa. Pale mucous membranes and skinsb. Weakness, loss of stamina, and exercise intolerance,Hypersensitivity to cold ,fever. c. Tachycardia and polypnea,Heart murmur. anemia associated cardiac disease: • Hb<30g/L more than 2 months • heart enlargement • ST depression

6. d. headache,dizzinesse.anorexia,nauxea,abdominal fullness diarria or constipation, Icterus.f.menstruation disorder or amenorreahemoglobinuriag. Shock if >1/ 2blood volume lost in short period.

7. C. Laboratory findings1. The Hct is the easiest, most accurate method for detecting anemia. Its result should be interpreted with knowledge of the hydration status and any alteration caused by splenic contraction.

8. 2. Hb and RBC may be used to further classify the anemia.

9. II. ClassificationA. Size (MCV) and Hb Concentration (MCHC)1. Normocytic, macrocytic, microcytic.2. Normochromic, hypochromic. (Hyperchromia does not occur)

10. Type MCV(fl) MCHC(%) MCH(pg) disorder Macro >100 >32 32-35 megaloblastic anemia MDS Normo 80-100 26-32 32-35 aplastic anemia,blood lost, hemolytic anemia Micro <80 <26 <32 iron deficiency anemia sideroblastic anemia thalassemia

11. B. Bone marrow response1.Regenerativea. Bone marrow actively responds by increasing its production of RBC’s.b. Findings:(1) Polychromasia.(2) Reticulocytosis

12. .(3) Macrocytosis (increased MCV) and hypochromia associated with reticulocytosis.(4) Hypercellular bone marrow with a low M/E ratio.(5) Increase in MCV and RDW

13. c. The presence of regeneration suggests an extramarrow cause. (1) Blood loss (2) Erythrocyte destruction (hemolysis) d. Bone marrow examination would reveal erythropoietichyperplasia .

14. 2. Non-Regenerative a. Inadequate bone marrow response because of a bone marrow disorder. b. Polychromasia and reticulocytosis are absent.

15. C. Pathophysiologic mechanism • Blood loss–hemorrhagic anemia. • 2. Accelerated erythrocyte destruction–hemolytic anemia. • 3. Reduced or defective • erythropoiesis

16. ANEMIA FROM ACCELERATED ERYTHROCYTE DESTRUCTION (HEMOLYTIC ANEMIA)

17. A. Clinical findings 1. Clinical signs of hemorrhage are absent. 2. Jaundice may be seen in acute and severe cases. 3. Hemoglobinuria and red plasma is seen if significant intravascular hemolysis occurs

18. B. Laboratory findings 1. Reticulocyte counts are higher in hemolytic anemias than external hemorrhagic anemias 2. Plasma protein concentration is normal or increased.

19. 3. Neutrophilic leukocytosis and monocytosis may occur. 4. Evidence of Hb degradation (hyperbilirubinemia, hemoglobinuria). 5. Abnormal erythrocyte morphology (Heinz bodies, erythrocytic parasites,spherocytes, or poikilocytes).

20. I. Differentiation of the Causes of Hemolytic Anemias A. Extravascular hemolysis

21. 1. Mechanisms • Autoimmune Mediated--Antibody and/or C3 mediated ( AIHA, infection, drug,immune system disorder) • b. Decreased erythrocyte deformability • (a)Shistocytes of microangiopathic anemia • (b) Spherocytes of immune-mediated anemia • (c) Parasitized erythrocytes • (d) Heinz body-containing cells

22. c. Reduced glycolysis and ATP content of the erythrocyte( PKdeficiency) d. Increased macrophage activity (hypersplenism)

23. e. Intravascular causes of hemolysis do not lyse all erythrocytes; some altered cells may remain that are removed by phagocytosis.

24. 2. Clinical and laboratory characteristics of phagocytic (extravascular) hemolysis. • Usually chronic with insidious onset. • b. A regenerative response. • c. Hemoglobinemia and hemoglobinuria are absent.

25. d. Hyperbilirubinemia e. Neutrophilia, monocytosis, and thrombocytosis f. Splenomegaly.

26. h. Low-grade extravascular hemolysis occurs in many anemias that are primarily nonhemolytic (e.g., anemia of chronic renal disease,iron-deficiency anemia). Referred to as the “hemolytic component” of other types of anemia

27. B. Intravascular hemolysis–Erythrocytes are destroyed within the circulation, releasing hemoglobin into the plasma where it is either removed by the liver or excreted by the kidneys.

28. 1. Mechanisms: The erythrocyte membrane must be significantly disrupted to allow escape of the Hb molecule into the plasma. Most of the mechanisms of intravascular hemolysis are extrinsic or extracorpuscular defects– the erythrocyte is initially normal.

29. Complement-mediated lysis. (neonatal isoerythrolysis and transfusion reactions, PNH ) b. Physical injury(Traumatic ,microangio- pathic anemia, DIC,Coagulation,Vasculitis) c. Oxidative injury (Heinz body,methemo- globin) d.Osmotic lysis( hypotonic intravenous fluids)

30. e. Other membrane alterations. (1) Castor beans–ricin. Causes direct lysis (2) Snake venoms (3) Bacterial toxins (4) Parasites (Babesia)

31. 2.Clinical and laboratory characteristics of intravcascular hemolytic anemia. • Most cases present as peracute or acuteepisodes. b. History may reveal exposure to causative drugs or plants, recent transfusion of blood, or recent ingestion of colostrum. c. A regenerative response occurs, but it may not be evident in early stages.

32. d. Hemoglobinemia is the principal feature of intravascular hemolysis. (1)Red discoloration of plasma (2) Increased MCHC e. Hemoglobinuria f. Hemosiderinuria g. Hyperbilirubinemia

33. h.Additional laboratory findings may include schistocytes, keratocytes, Heinz bodies, erythrocytic parasites, positive Coombs’ test.

34. ANEMIA FROM REDUCED OR DEFECTIVE ERYTHROPOIESIS reduced or defective erythropoisis long or onset insidious clinic course

35. I. General considerations. A. Mechanisms: 1. Precursor cells Nutrients (iron and B vitamins) Stimulation (erythropoietin)

36. 2. Bone marrow failure( intramarrow disease and extramarrow causes) 3. Bone marrow failure may be selective for the erythroid series or may also affect the other cell lines.

37. B. Bone marrow response • When the number of precursor cells or erythropoietic stimulation is inadequate, the erythroid marrow is hypocellular. 2. Maturation abnormalities which characterize the nutritional deficiencies, are associated with a Hypercellular marrow and ineffective erythropoiesis..

38. 3. All degrees of bone marrow failure can occur, from complete aplasia to a suboptimal response of the erythroid marrow following hemorrhage or hemolysis.

39. II. Differentiation of anemias caused by reduced or defective erythropoiesis. erythrocyte morphology, • blood neutrophil • platelet numbers • bone marrow cellularity.

40. A. Normocytic, normochromic anemia; normal or increased neutrophil and platelet numbers; increased M/E ratio caused by hypocellular erythroid marrow. 1. Anemia of erythropoietin lack. a. Chronic renal disease. Anemia proportional to severity of the uremia.

41. b. Endocrinopathies (1) Cushings (2) Hypoandrogenism (3) Hypopituitarism

42. 2. Anemia of chronic disorders (ACD) a. Occurs in chronic infectious, inflammatory, or neoplastic disorders. b. Cytokines involved with the inflammatory process initiate the anemia. c. Erythrocyte life span reduced

43. d. Laboratory findings include: (1) Low serum iron (2) Low total iron binding capacity (3) Increased bone marrow macrophage iron (4) Mild-moderate anemia that is usually nonprogressive

44. 3. Pure red cell aplasia a. Characterized by a selective loss of erythroid precursors in the bone marrow. b. Thought to be immune mediated. 4. Unknown mechanisms a. Liver disease b. Vitamin E deficiency

45. B. Normocytic, normochromic anemia; neutropenia and/or thrombocytopenia; M/E ratio is difficult to determine because of hypocellularity.

46. 1. Aplastic anemia a. pancytopenia. b. shorter life spans of the cells. c. Causes (1) Drugs, chemicals, plants (2) Irradiation (3) Cytotoxic T cells or antibody (4) Infectious agents

47. 2. Myelophthisic anemia a. The bone marrow is physically replaced by an abnormal proliferation of cells. (1) Myeloproliferative disorders–leukemias (2) Myelofibrosis (3) Osteosclerosis (4) Diffuse granulomatous osteomyelitis (5) Metastatic cancer

48. 3. Anemia caused by infectious agents a. Ehrlichiosis(埃里西提病） b. FeLV（猫白血病病毒）

49. C. Microcytic, hypochromic anemia; variable neutrophil and platelet number; usually a hypercellular marrow with a variable M/E ratio.

50. 1. Iron deficiency a. Chronic hemorrhage b. Dietary deficiency, especially in young milk-fed c. Ineffective erythropoiesis early;