Hematologic Diseases

1. Hematologic Diseases General Introduction of Hematology

2. Components and functions of blood • Two major components: blood cells(cellular fraction) plasma (non-cellular fraction) • Primary functions : red blood cell: to transport O2 and CO2 neutrophils: to destruct microorganisms lymphocyte: to mediate immune reaction

3. T cell: (thymus dependent ): cell- mediated immune B cell: (BM dependent ): humoral-mediated immune Monocytes: to phagocytize and modulate immune reaction Eosinophils: to be involved in IgE immune reaction Basophils: to be involved in type I hypersensitivity

4. Plasma: relevant to coagulation factors, immunoglobulins and complements

5. Compositions of hematopoietic organs • Hematopoietic organs: blood, bone marrow, liver,spleen, lymph nodes • Structure of bone marrow: outside cortex: inside medulla : 50% hematopoietic and 50% fat tissues hematopoietic cells are arranged in cords around sinusoid mature cell are released into sinusoid through endothelia cell of sinus abundant blood vessles are linked to sinusoid

6. Hematopoiesis in adult: To be confined to bone marrow and lymphocyte • Hematopoiesis in fetal: Yolk sac, liver and spleen • Extramedullary hematopoisis:

7. Process of hematopoiesis • Hematopoietic cell: Pluripotential stem cell CD34+/ CD38- A small compartment of stem cells A large compartment of proliferating cells of committed lineage A large compartment of maturing cells of both myeloid and lymphoid

8. Hematopoietic growth factor: Erythropoietin(EPO): G-CSF,GM-CSF : Thrombopoietin (TPO), IL-11:

9. Classification and characteristics of hemayologic diseases • Diseases of red blood cells: Aplastic anemia, IDA, hemolytic anemia, megaloblastic anemia, thalassemia, sideroblastic anemia • Diseases of white blood cells: Leukepeania, leukecytosis, leukemia, lymphoma, myeloma, myelodisplastic syndrome(MDS) • Diseases of bleeding and thrombosis: ITP, DIC, hemophila

10. Characteristics of blood diseases • Numerous types • Low incidence • High mortality • Poor prognosis • Multi-system involved • Lab-test dependent diagnosis

11. Diagnosis of hematopoietic diseases • History: symptoms, period of diseas, inductive factors, personal history, occupation history, family history, diet habit, drug take-in history, age, sex • Physical examination: pallor, purpura, fever, sternum tenderness, lympho node, hepatomegaly, splenomegaly • Laboratory tests: BRT, morphology, bone marrow biopsy, DIC examination, hemolytic examination, biochemical and immunologic examination, chromosome banding technique, FCM detection

12. The progresses in hematologic diseases • Immunotherapy: leukemic vaccine, dendritic vaccine, cytokine gene-transduced vaccine, recombinant hematopoietic growth factor : rIL-2,rIL-11,rTPO, rEPO,rGM-CSF, • Hematopoietic stem cell transplantation: BMT,peripheral stem cell transplantation, cord blood transplantation • Gene therapy: hemophilia, thalassemia, leukemia, gene chip

13. Introduction of anemia • Concept of anemia Anemia is a syndrome, not a name of a disease Anemia is a common symptoms in many diseases In anemia status, Hb and RBC are lower than normal Decreases of Hb is more important in judge degree of anemia

14. Causes and mechanisms of anemia The injury of progenitor of erythrocyte: physical,chemical, viruses factors The lack of hematopoietic factors: ferritin,vitB12, folic acid,vitB6,vitC The lack of bone marrow tissues: leukemia, lymphoma,MM, solid tumor infiltrate to bone marrow Increase of red blood cell destruction: hereditary and acquied hemolytic anemia: abnormal of RBCmembrane, Hb, RBC enzymes

15. Classification of anemia • According to the causes and mechanisms of anemia to type: Decrease of red blood cell production(AA, IDA,leukemia) Increase of red blood cell destruction (hemolytic anemia) Acute or chronic blood loss, GI tumor hypermenorrhea, hemorrhiod, hook-worm

16. Accoding to morphology: Microcytic hypochromic anemia:IDA Megalocytic anemia: deficiency folic acid and vitB12 Normal erythrocytic anemia: AA, hemolytic anemia

17. Clinic features of anemia • Shortness of breath on exertion Palpitation Tiredness, weakness or fatigue Faintness tinnitus Headache Spots before the eyes

18. Factors influencing symptoms of anemia: The rapidity of onset and severity of anemia The ability of patients to make cardiovascular compensations Age: old person with severe symptoms Sex: female with severe symptoms

19. Diagnosis of anemia • Whether anemia exist • How severe anemia is • Original causes diseases of anemia

20. Treatment of anemia • Primary diseases and causes • Supportive treatment: blood transfusion • Hematopoietic factors: EPO, iron, folic acid vitb12 • Immune suppressor: CsA, Prednision, • Splenectomy: HS AIHA • BMT: AA, PNH, MDS

21. Iron Deficiency Anemia(IDA)

22. Concept and characters of IDA IDA is usually caused by chronic blood loss or lack of hematopoietic nutrient ferritin by malabsorption. The morphologic characteristic of IDA is microcytic hypochromic anemia. IDA is one of the most common nutritious anemia in the world.

23. Iron metabolisms • In general, iron metabolism depends on a precise balance between iron absorption and excretion. • Iron is supplied by food,10 to 20 mg of iron is presented in the average daily food, which is enough to healthy adult male and nonmenstrating female. • Iron absorption occurs mainly in the duodenum and proximal jejunum. Gut mucosal cells regulate absorption by storage iron. • Normally, 5-10% dietary iron is absorbed.

25. Iron enters the mucosal cells is either bound to transferrin or transported into the portal circulation or remains in the mucoscal cell . Transferrin delivers either to bone marrow tissues for Hb synthesis or to liver to store. • The reticuloendothelial system phagocytoses senescent red blood cells. About 2/3 iron obtained by metabolism of Hb within the reticuloendothelial system binds rapidly to plasma transferrin for transport to marrow reuseness. The others is stored within the macrophage as ferritin or hemosiderin.

26. Approximately 1mg of iron is lost daily by the adult male and nonmenstruating female via sweet, urine, stool. Menstruating females lose an additional 10-30mg of iron with each menstrual period. • Daily needed iron: adult male: 1mg/d children: 2mg/d menstruating female: 3mg/d pregnant and breast feeding woman: 4mg/d

27. Causes and primary disease of IDA • Inadequate dietary iron related to inappropriate food , Iron deficiency occurs more commonly in populations whose diets often lacking of meats. • Increased iron requirement: woman with menstruation and pregnancy. Infancy and adolescence when growth is rapid. • Decreased iron absorption: partial and total gastrectomy and achlorhydria.

28. Blood loss: predominant cause of iron deficiency young woman-menstrual blood loss: during a normal menstrual period, approximately 32mg iron may be lost(2:1) oldman and non-menstrual woman-gastro-intenstinal blood loss : GI tumor, young man blood loss – peptic ulcer, hemorrhoid, children blood loss – hookworm disease,

29. Clinical features of IDA • General symptoms of anemia: palpitation, shortness of breath, tiredness, headache • Specific symptoms of IDA: spoon-shaped nails(koilonychia) with dry , brittle, ridged changes • A hunger for unusual substances : ice, clay, hair, • Digestive symptoms: sore tongue, atrophy of the gastric mucosa, plummer-vinson syndrome

33. Laboratory tests of IDA BRT: Hb decrease, WBC and platelet are normal Bone marrow: microcytic hypochromatic changes in morphology, intracellular iron is <15%, extracellular iron is negative Iron metabolism index: serum iron decrease, serum ferritin protein decrease, total iron binding capacity increase

38. Diagnosis and differential diagnosis • History • Morphologic characteristics of RBC • BM examination and iron staning • Serum iron and serum ferritin level • Diagnostic treatment with iron

39. Treatment of IDA • Treatment of primary diseases • Treatment with iron –ferrintherapy • Oral iron: ferrous sulfate: 300mg tablet daily and gradually increase to three time daily post meal • Injection iron: iron dextran: im, 50-100mg daily,total iron needed: ( Hb15g/dl -patient’s Hbg/dl ) x300mg+500mg

40. Hemolytic anemia

41. Introduction • Hemolytic anemia results from an increased rate and speed in RBC destruction. • BM has the capacity to compensate production of RBC from 6-8 folds. Compensated hemolytic disease has a persistently elevated reticulocyte count with a normal Hb. • In situ hemolysis: RBC are destructed in BM before they are released into blood (<10%)

42. Extravascular hemolysis: RBC are phagocytosed by reticuloendothelial system and removed from the circulation because of inflexible prematurely. AIHA, HS, • Intravascular hemolysis : RBC are actually lysed in the circulation and blood vessels. PNH, DIC

43. physiopathology of hemolytic anemia • Increased hemolysis: Increased serum bilirubin Increased urine urobilinogen Decreased serum haptoglobin • Increased production of RBC: Reticulocytosis and polychromasia Erythroid hyperplasia in BM

44. RBC damage: Morphology: fragment, micro-spherocytes, spherocytes Increased osmotic fragility Short RBC survival time Hemoglobinemia and hemoglobinuria

45. Classification of hemolytic anemia • RBC intrinsic abnormal Memberane (hereditary spherocytosis) Enzyme (G-6PD deficiency) Hemoglobinopathy( sick cell diseases) Globin synthesis (thalassemia)

46. RBC extrinsic abnormal(usually acquired) Abtibody induced (coomb’s positive hemolytic anemia): worm antibody and cold antibody Drug induced (penicillin) Toxin mediated (burns, sepsis) Mechanical hemolysis(heart valve surgery)

47. Clinic features of hemolysis • General symptoms of anemia • Jaundice • Hemoglobinuria • Acute hemolysis: high fever, cold, pain of back, nausea and vomit, occurs rapidly with intravascular hemolysis • Chronic hemolysis: splenomegaly, uncler on ankle skin and bile pigment stone, occurs slowly with extravascular hemolysis.