1 ANEMIA Tongji Medical College, Huazhong University of Science and Technology

2 Introduction Anemia is a commonly encountered clinical symptom that is caused by an acquired or hereditary abnormality of red blood cells (RBC) or its precursors, or may be a manifestation of an nonhematologic disorder hematologic adj. hematology n.

3 Definition Anemia is defined as a decrease in the circulating RBC or hemoglobin and a corresponding decrease in the oxygen- carrying capacity of the blood. Normal values of the hemogram: TEST WOMEN MEN HCT (%) Hb (g/L) RBC Count(10 12 /L) HCT:Haematocrit Hb:hemoglobin

4 Definition A decrease in any of these values (HCT, Hb, RBC count) is called anemia. TEST WOMEN MEN HCT (%) ＜ 37 ＜ 42 Hb (g/L) ＜ 110 ＜ 120 RBC Count(10 12 /L) ＜ 4.0 ＜ 4.5 They can be altered by the plasmatic volumes. Difference between women and men values are due to androgen hormones. For pregnant women, Hb ＜ 100g ／ L

5 cell morphological classification cell morphological type MCV （ fl ） MCHC (%) Macrocytic anemia ＞ ～ 35 Normocytic anemia 80 ～ ～ 35 Microcytic hypochromic anemia ＜ 80 ＜ 32 MCV ： mean corpuscular volume ； MCHC ： mean cell hemoglobin concentration

6 Macrocytic anemia Megaloblastic anemias ( folic acid and vitamin B 12 deficiency) Alcoholism Drugs Liver diseases Primary bone marrow disorder Hypothyroidism Splenectomy

7 Normocytic anemia Chronic disease anemia (hepatic, renal or endocrine disorders) Primary bone marrow disorders (aplasia, myelodisplasia, myelofibrose, hematologic and solid tumors, HIV infection, granulomas Hemolytic anemia

8 Microcytic anemia Iron Deficiency Thalassemia

9 Classification according to severity Degree Hb （ g/L ） Mild anemia 90 ～ 120 Moderate anemia 60 ～ 90 Severe anemia ＜ 60 Very Severe anemia ＜ 30

10 Classification: according to Bone marrow proliferative degree Bone marrow anemia hyperplasia IDA, hemolytic anemia, blood loss anemia Hypoplasia AA, PRCA Dysmaturity (ineffective erythropoiesis) myelodysplastic syndrome ( MDS ) Megaloblastic anemias

11 Classification: according to etiology/pathogenesis etiology/pathogenesis Decreased RBC production Increased RBC destruction Blood loss

12 Classification: according to etiology/pathogenesy Decresed RBC production Anemia 1.BM stem cells abnormality AA 2.BM injured by abnormal tissues/cells Leukemia 3.Cell dysmaturity (1). DNA dyssynthesis Megaloblastic anemias (2). Hb dyssynthesis IDA 4. Abnormality in haematopoiesis modulation AA

13 Classification: according to etiology/pathogenesis Increased RBC destruction Anemia 1.RBC internal defect (1)RBC membrane defect acquired: PNH hereditary : hereditary spherocytosis (2) enzyme deficiency: G6PD deficiency (3) Hb abnormality hemoglobinopathy (4) porphyrin metabolism porphyrinopathy 2. Exopathic immunologic, chemical, biological, or phisical factors

14 Classification: according to etiology/pathogenesy Blood loss 1.Acute blood loss 2.Chronic blood loss

15 Related factor; 1.cause of anemia 2.Degree of decrease of oxygen carrying capacity 3.Degree of decrease of blood volume 4.Speed of anemia genesis 5.Compensation and tolerance of blood and other Clinical manifestation

16 1 、 nervous system ： headache 、 dizzy 、 dispirited 、 faint 、 ear noises 、 dim eyesight 、 memory impairment 、 impaired concentration ； acroanesthesia, intelligence development abnormality 2 、 skin and mucosa ： pallor ； rough ； ulcer, stained yellow, Koilonychia 3 、 espiratory apparatus ： accelerated breathing ； short breath 、 4 、 digestive system ： abdominal distention 、 anorexia, bowel disturbance, swallow foreign body sensation ； Decreased food appetite; mirror surface tongue Clinical manifestation

17 5 、 urinary system ： bilirubinuria 、 hemoglobinuria 、 urinary siderosis ； ARF 6 、 circulating system ： peripheral vaso-constriction ， Palpitation, congestive heart failure 7 、 endocrine system ： endocrine functional abnormality 8 、 immune system ： Clinical manifestation

18 9 、 hematological system ： peripheral blood: blood cell count, appearance and biochemical component ； plasma,serum hematopoietic organ :BM, liver, spleen, lymph node 10 、 genital system ： Clinical manifestation

19 complete diagnosis 1.anemia 2.Degree of anemia 3.Classification of anemia 4.Cause of anemia Diagnosis

20 History( inquisition ): 1.Present history(symptoms and their duration) 2.Past history( Gastrectomy, haemorrhoids, peptic ulcer ) 3.Family history(hereditary background) 4.Menses and childbearing history 5.Diet habit 6.Exposure to risk factors(such as chemicals or toxins) Diagnosis: history

21 Diagnosis: Physical examination 1.Pale (lip, palpebral conjunctiva, finger nail ) 2.accompanying symtoms hemolytic bleeding infiltration infection malnutrition

22 laboratory investigation : 1.Peripheral blood(PB) (1)blood routine test : RBC, HCT,Hb, Erythrocyte indexes(MCV,MCH,MCHC) (2)blood smears (3)Reticulocyte count(Ret) 2.Bone marrow(BM) aspiration 3.investigation for cause: urine routine test, renal function test, Occult blood in stools, X ray or endoscope for stomach and bowel Diagnosis: laboratory investigation

23 1. Treatment for original cause 2. Treatment for symptoms transfusion haemostasis anti-infection supportive therapy Treatment

24 Break

25 Aplastic anemia (AA)

26 Definition The term aplastic anemia describes a clinical syndrome in which there is a deficiency of red cells,neutrophils, and monocytes,and platelet without mophological evidence of another marrow disorder. Marrow examination shows a near absence of normal hematopoietic precursor cells and fatty replacement. It is a life-threatening hematologic disease.

27 Definition The term pancytopenia If all of the cell lines(erythrocytic, leukocytic, and thrombocytic) are affected and decrease, the disorder is referred to as pancytopenia. If only one cell line is involved, it is usually the erythrocytic cells. (pure red cell anemia,PRCA)

28 Etiology and pathogenesis Etiology 1.Idiopathic about 65% of all cases 2.Acquied (1)chemicals Benzene (2)drugs chloramphenicol (3)radiation (4)viruses Epstein-Barr virus, hepatitis virus (5)miscellaneous pregnansy, connective tissue disorders 3.Hereditary

29 Etiology and pathogenesis Pathogenesis 1. “Seeds” Absent or defective stem cells 2. “Soil” Abnormal bone marrow microenviroment 3. “Worms ” Abnormal regulatory cells or factors Immue-mediated supression of hamatopoiesis

30 Clinical manifestation and classification Clinical manifestation Anemia normochromic normocytic Bleeding Infection Classification 1.severe aplastic anemia （ SAA ） : type I type II 2.non-severe aplastic anemia （ NSAA ）

31 1. peripheral blood: pancytopenia normochromic and normocytic anemia SAA: （ 1 ） Hb < 30g/L; reticulocyte <1 ％， absolute value ＜ 15×10 9 ／ L 。 （ 2 ） neutrophil ＜ 0.5×10 9 ／ L （ 3 ） platelet ＜ 20×10 9 ／ L Very severe aplatic anemia(VSAA ）： SAA- Ⅰ neutrophil ＜ 0.2x10 9 /L. NSAA ： （ 1 ） Hb 40 ～ 60g/L ， Ret ＞ 1 ％， its absolute value is lower than normal. （ 2 ） neutrophil ＞ 0.5×10 9 ／ L ， relative value of lymphocyte increases. （ 3 ） BPC(blood platelet count) ＞ 20×10 9 ／ L Laboratory findings

32 2 、 Bone marrow smear Bone marrow hypoplasia Hematopoietic cells decrease so proportion of non hematopoietic cells (lymphocyte, monocyte, plasmacyte, basophil ） increases. Platelet is rare and NAP count increases. SAA no megakaryocyte NSAA residual areas of hematopoiesis(hot spot) megakaryocyte decreased or absence Laboratory findings

33 3 、 Bone marrow biopsy ： better than smear Red pulp is replaecd by fatty tissues. Hematopoietic cells is less than half of normal normal situation ， ratio of fatty tissues increses. Megakaryocyte is rare or absent. 4 、 Bone marrow ECT ： It helps to evaluate remained hematopoietic activity. Laboratory findings

34 1.pancytopenia, reticulocyte absolute value decreases. 2.no splenormegaly 3.at least on area of hypoplasia in bone marrow(significant reduction of megakaryocytes is needed if hyperplasia is found ). Non- hematopoietic cells increase. 4. Elimination of other diseases which may cause pancytipenia such as PNH, MDS,MFMyelofibrosis, acute arrest of hemopoiesis, etc. 5. Common therapy for anemia is ineffective. Diagnosis

35 Differentiation between SAA and NSAA SAA NSAA Progress acute chronic bleeding severe mild often occurred in internal organ often occurred in skin and mucosa infection severe sepsis mild Upper respiratory tract PB （ ×10 9 /L ） Neutrophil ＜ 0.5 ＞ 0.5 BPC ＜ 20 ＞ 20 Ret absolute value ＜ 15 ＞ 15 BM most areas of hypoplasia hypoplasia or hyperplasia Prognosis bad, die in 6 to 12 months better ， a few patients may die

36 1 、 paroxysmal nocturnal hemoglobinuria （ PNH ） 2 、 myelodysplastic syndrome （ MDS ） 3 、 hypoproliferative leukemia 4 、 acute arrest of hemopoiesis 5 、 Myelofibrosis ６、 autoantibody mediated pancytopenia Differential diagnosis

37 1 、 withdrawal of etiologic agents （ acquired AA ） 2 、 supportive care ： （ 1 ） anemia ： RBC transfusion(Hb ＜ 60g/L ） （ 2 ） bleeding ： BPC<20×10 9 ／ L, spontaneous bleeding platelet transfusion （ 3 ） infection ： 1aminar flow ward, cleaning of skin,mouth cavity,anus and diet Antibiotics used early and strongly Neutrophil transfusion is not recommended Therapy

38 3 、 SAA （ 1 ） hematopoietic stem cell transplantation(HSCT) ： allo-HSCT （ 2 ） Immunosuppressive therapy ： a ． antilymphocyte globulin （ ALG ） or antilymphocyte globulin （ ATG ） b. High dose methylprednisolone （ HDMP ） C ． cyclosporin A （ CsA ） Combination of ATG/ALG, CsA and HDMP (3) Hemopoietic growth factor: EPO, granulocyte colony-stimulating factor (G-CSF), IL-11 Therapy

39 4 、 NSAA a ． androgen ： b ． CsA c ． Other drugs ： Securinine 、 Levamisole d ． combination of traditional Chinese medicine and western medicine Therapy

40 Thank you