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GENERAL  HEMATOLOGY
RED CELL  DISORDERS BONE MARROW FAILURE SYNDROMES BLEEDING  DISORDERS HEMATOLOGY PRIMARY  DECREASE PRODUCTION INCREASED DESTRUCTION POLYCYTHEMIA ANEMIA SECONDARY LEUKEMIAS CHRONIC ACUTE MYELOID MYELOID LYMPHOID LYMPHOID DIAMOND BLACKFAN APLASTIC ANEMIA PLATELET DISORDERS COAGULATION DEFECTS VASCULAR BLOOD LOSS
PRIMARY  DECREASED  PRODUCTION INCREASED  DESTRUCTION POLYCYTHEMIA ANEMIA SECONDARY BLOOD LOSS NUTRITIONAL  ANEMIAS FOLIC ACID DEF IRON VITAMIN B12 DEF HEMOLYTIC  ANEMIAS MEMBRANE DEFECTS INFECTION IMMUNE RED CELL DISORDERS
ANEMIA ,[object Object]
Etiopathogenesis of Anemia Iron, folic acid, proteins . . . Bone Marrow DEFICIENCY ANEMIA MARROW FAILURE Circulation BLOOD LOSS HEMOLYSIS Acute Chronic Intravascular Extravascular 1 2 4 3
Hematologic Values During Infancy and Childhood 47 (42-52) 16 (14.0-18.0) Adult male 42 (37-47) 14 (12.0-16.0) Adult female 38 (34-40) 13 (11.0-16.0) 7-12 yr 37 (33-42) 12.0 (10.5-14.0) 6 mo -6 yr 36 (31-41)  12.0 (9.5-14.5) 3 months 50 (42-66) 16.5 (13-20.0) 2 weeks 55 (45-65) 16.8 (13.7-21.1) Cord Blood HEMATOCRIT HEMOGLOBIN  AGE
Classification of Anemia based on Red Cell MCV Aplastic anemia Leukemia Folate deficiency Vitamin B12 deficiency Liver disease Normal Chronic Disease Hereditary Spherocytosis Blood loss Early iron deficiency Marrow infiltration Thalassemias Iron Deficiency Lead poisoning Chronic Diseases MCV High MCV Normal MCV low
Which of the RBC’s in the foll. blood smears is considered- 1. Normocytic, normochromic 2. hypochromic, microcytic 3. macrocytic B A C
Physiologic Anemia of Infancy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
[object Object],[object Object],[object Object],[object Object],Daily,  a normal adult, destroys  15 ml of senescent red cells  and produces an equal quantity of new red cells.  For the daily production of erythrocytes, about  15 mg of iron  is  required.
[object Object],[object Object],[object Object]
If the body is capable of recycling iron, then why is there iron deficiency? ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
Physiologic increase in iron requirements FEMALE infancy menopause Adolescence pregnancy childhood male
Pathologic causes of iron deficiency anemia ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
IRON DEPLETION IRON DEFICIENT   ERYTHROPOIESIS IRON DEFICIENCY ANEMIA
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],LABORATORY DIAGNOSIS
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Repletion of iron stores 1-3 mo Increase in hemoglobin level 4-30 days Reticulocytosis (peak at 5-7 days) 48-72 hour Initial bone marrow response: erythroid hyperplasia 36-48 hour Replacement of intracellular iron enzyme 12-24 hour Response Time after iron administration Response to iron therapy in iron deficiency anemia
[object Object],[object Object],[object Object],Megaloblastic Anemias
BONE MARROW A B
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Folic Acid Deficiencies Megaloblastic Anemias
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],VITAMIN B 12  DEFICIENCIES Megaloblastic Anemias
HEMOLYTIC ANEMIAS ,[object Object],HEMOLYTIC  ANEMIAS INTRAVASCULAR EXTRAVASCULAR
HEMOLYTIC ANEMIAS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
IMMUNE HEMOLYTIC ANEMIAS ,[object Object],[object Object],[object Object],[object Object],[object Object]
Immune Hemolytic Anemia ,[object Object],[object Object],[object Object],[object Object],[object Object]
DISORDERS OF HEMOGLOBIN SYNTHESIS HEMOGLOBIN  HEME GLOBIN Cong. Erythropoietic  porphyria ,[object Object],[object Object],[object Object],[object Object]
THE  HEMOGLOBINS 2 α   2 γ Hemoglobin F (Fetal) 2 α  2 δ Hemoglobin A2  2 α   2 β Hemoglobin A1 (Adult) Polypeptides Hemoglobin
Thalassemia syndromes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Alpha Thalassemia ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Thalassemia syndromes
Beta Thalassemia ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Thalassemia syndromes
Management ,[object Object],[object Object],[object Object],[object Object],[object Object],Thalassemia syndromes
Complications ,[object Object],[object Object],[object Object],Thalassemia syndromes
Hereditary Spherocytosis ,[object Object],[object Object],[object Object]
Hereditary Spherocytosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Hereditary Spherocytosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Hereditary Spherocytosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
G6PD Deficiency
Function of Red Cells ,[object Object],[object Object],[object Object],[object Object],G6PD Deficiency
Oxidant Defenses in the Red Cell ,[object Object],[object Object],[object Object],[object Object],G6PD Deficiency
Glutathione anti-oxidant system 2GSH + H2O2 GSSG + 2 H2O Reaction 1 GSSG + NADPH 2 GSH + NADP Reaction 2 GLU PEROXIDASE GLU REDUCTASE G6PD Deficiency
Role of Gluc 6 Phosphate  Dehydrogenase ,[object Object],[object Object],Gluc 6 PO4  + NADP 6 Phosphogluconate  +  NADPH G6PO4 dehydrogenase G6PD Deficiency
Damage to the Red Cell in G6PD deficiency brought about by oxidant stress ,[object Object],[object Object],[object Object],[object Object],[object Object],G6PD Deficiency
CHRONIC ACUTE MYELOID MYELOID LYMPHOID LYMPHOID LEUKEMIAS AML M0-M7 ALL L1-L2 CML CLL
CLASSIFICATION OF ACUTE LEUKEMIAS (FAB) assoc. with difficulty in aspirating the marrow megakaryoblastic AML M7 Erythroleukemia AML M6 Monocytic AML M5 Granulocytic and monocytic AML M4 Commonly associated with DIC Promyelocytic AML M3 With granulocytic maturation AML M2 Without maturation AML M1 Undifferentiated AML M0 ACUTE MYELOGENOUS LEUKEMIA
CLASSIFICATION OF ACUTE LEUKEMIAS (FAB) LEUKEMIAS Mature B cell (burkitt’s lymphoma)-bad prognosis T-cells (bad prognosis) Best prognosis (pre-B cell lineage) Large, finely stippled chromatin, mod. cytoplasm, deeply basophilic cytoplasm with vacuolations ALL L3 Large cells, cleft nucleus, prominent nucleoli, mod. cytoplasm ALL L2 Small cells predominate, homogenous nuclear chromatin, inconspicuous nucleoli, scanty basophilic cytoplasm ALL L1 ACUTE LYMPHOCYTIC LEUKEMIA
Generalities ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],LEUKEMIAS
PLATELET  DISORDERS COAGULATION  DEFECTS VITA K DEF BLEEDING DISORDERS HEMOPHILIAS QUALITATIVE QUANTITATIVE TRAUMA VASCULAR PURPURA VITAMIN DEF VASCULAR VWD CONN. TISS. DSE ITP INFECTIOUS SCURVY EHLER DANLOS SYNDROME DIC DIC THROMBASTHENIAS
[object Object]
Normal hemostasis Vessel injury Collagen exposure TXA2, ADP Platelet aggregation 1  hemostatic plug Stable hemostatic plug Vasoconstriction    blood flow Tissue thromboplastin Blood coag. Fibrin
Screening Tests of Hemostasis ,[object Object],[object Object]
Clinical manif typically assoc with specific hemostatic disorder ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Clinical manif typically assoc with specific hemostatic disorder ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Hemostatic Screening Tests ,[object Object],[object Object],[object Object],[object Object]
Prothrombin Time Intrinsic Surface XII Prekallikrein HMW -K XI  XIa IX  IXa VIIIa Phospoholipid Ca++ Extrinsic VII-VIIa Tissue Factor Phospholipid Ca++ X  Xa Va Phospholipid Ca++  Prothrombin(II)  Thrombin(IIa) Fibrinogen(I)  Fibrin
Activated Partial Thromboplastin Time Intrinsic Surface XII Prekallikrein HMW -K XI  XIa IX  IXa VIIIa Phospoholipid Ca++ Extrinsic VII-VIIa Tissue Factor Phospholipid Ca++ X  Xa Va Phospholipid Ca++  Prothrombin(II)  Thrombin(IIa) Fibrinogen(I)  Fibrin
Acquired platelet dysfunction with eosinophilia (APDE) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
APDE ,[object Object],[object Object],[object Object],[object Object],[object Object]
APDE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
APDE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Henoch-Schonlein purpura ,[object Object],[object Object],[object Object],[object Object]
Henoch-Schonlein purpura ,[object Object],[object Object],[object Object],[object Object]
Immune thrombocytopenic purpura ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Immune thrombocytopenic purpura ,[object Object],[object Object],[object Object],[object Object],[object Object]
Drug-induced thrombocytopenia ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
ACQUIRED PROTHROMBIN COMPLEX DEFICIENCY ,[object Object],[object Object],[object Object],[object Object],[object Object]
HEMOPHILIAS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
BLACKFAN-DIAMOND  ACQUIRED APLASTIC ANEMIA BONE MARROW FAILURE  FANCONI’S ANEMIA CONGENITAL APLASTIC ANEMIA TRANSIENT ERYTHOBLASTOPENIA OF CHILDHOOD (TEC)

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Hematology

  • 2. RED CELL DISORDERS BONE MARROW FAILURE SYNDROMES BLEEDING DISORDERS HEMATOLOGY PRIMARY DECREASE PRODUCTION INCREASED DESTRUCTION POLYCYTHEMIA ANEMIA SECONDARY LEUKEMIAS CHRONIC ACUTE MYELOID MYELOID LYMPHOID LYMPHOID DIAMOND BLACKFAN APLASTIC ANEMIA PLATELET DISORDERS COAGULATION DEFECTS VASCULAR BLOOD LOSS
  • 3. PRIMARY DECREASED PRODUCTION INCREASED DESTRUCTION POLYCYTHEMIA ANEMIA SECONDARY BLOOD LOSS NUTRITIONAL ANEMIAS FOLIC ACID DEF IRON VITAMIN B12 DEF HEMOLYTIC ANEMIAS MEMBRANE DEFECTS INFECTION IMMUNE RED CELL DISORDERS
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  • 5. Etiopathogenesis of Anemia Iron, folic acid, proteins . . . Bone Marrow DEFICIENCY ANEMIA MARROW FAILURE Circulation BLOOD LOSS HEMOLYSIS Acute Chronic Intravascular Extravascular 1 2 4 3
  • 6. Hematologic Values During Infancy and Childhood 47 (42-52) 16 (14.0-18.0) Adult male 42 (37-47) 14 (12.0-16.0) Adult female 38 (34-40) 13 (11.0-16.0) 7-12 yr 37 (33-42) 12.0 (10.5-14.0) 6 mo -6 yr 36 (31-41) 12.0 (9.5-14.5) 3 months 50 (42-66) 16.5 (13-20.0) 2 weeks 55 (45-65) 16.8 (13.7-21.1) Cord Blood HEMATOCRIT HEMOGLOBIN AGE
  • 7. Classification of Anemia based on Red Cell MCV Aplastic anemia Leukemia Folate deficiency Vitamin B12 deficiency Liver disease Normal Chronic Disease Hereditary Spherocytosis Blood loss Early iron deficiency Marrow infiltration Thalassemias Iron Deficiency Lead poisoning Chronic Diseases MCV High MCV Normal MCV low
  • 8. Which of the RBC’s in the foll. blood smears is considered- 1. Normocytic, normochromic 2. hypochromic, microcytic 3. macrocytic B A C
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  • 15. Physiologic increase in iron requirements FEMALE infancy menopause Adolescence pregnancy childhood male
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  • 17. IRON DEPLETION IRON DEFICIENT ERYTHROPOIESIS IRON DEFICIENCY ANEMIA
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  • 24. Repletion of iron stores 1-3 mo Increase in hemoglobin level 4-30 days Reticulocytosis (peak at 5-7 days) 48-72 hour Initial bone marrow response: erythroid hyperplasia 36-48 hour Replacement of intracellular iron enzyme 12-24 hour Response Time after iron administration Response to iron therapy in iron deficiency anemia
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  • 34. THE HEMOGLOBINS 2 α 2 γ Hemoglobin F (Fetal) 2 α 2 δ Hemoglobin A2 2 α 2 β Hemoglobin A1 (Adult) Polypeptides Hemoglobin
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  • 47. Glutathione anti-oxidant system 2GSH + H2O2 GSSG + 2 H2O Reaction 1 GSSG + NADPH 2 GSH + NADP Reaction 2 GLU PEROXIDASE GLU REDUCTASE G6PD Deficiency
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  • 50. CHRONIC ACUTE MYELOID MYELOID LYMPHOID LYMPHOID LEUKEMIAS AML M0-M7 ALL L1-L2 CML CLL
  • 51. CLASSIFICATION OF ACUTE LEUKEMIAS (FAB) assoc. with difficulty in aspirating the marrow megakaryoblastic AML M7 Erythroleukemia AML M6 Monocytic AML M5 Granulocytic and monocytic AML M4 Commonly associated with DIC Promyelocytic AML M3 With granulocytic maturation AML M2 Without maturation AML M1 Undifferentiated AML M0 ACUTE MYELOGENOUS LEUKEMIA
  • 52. CLASSIFICATION OF ACUTE LEUKEMIAS (FAB) LEUKEMIAS Mature B cell (burkitt’s lymphoma)-bad prognosis T-cells (bad prognosis) Best prognosis (pre-B cell lineage) Large, finely stippled chromatin, mod. cytoplasm, deeply basophilic cytoplasm with vacuolations ALL L3 Large cells, cleft nucleus, prominent nucleoli, mod. cytoplasm ALL L2 Small cells predominate, homogenous nuclear chromatin, inconspicuous nucleoli, scanty basophilic cytoplasm ALL L1 ACUTE LYMPHOCYTIC LEUKEMIA
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  • 54. PLATELET DISORDERS COAGULATION DEFECTS VITA K DEF BLEEDING DISORDERS HEMOPHILIAS QUALITATIVE QUANTITATIVE TRAUMA VASCULAR PURPURA VITAMIN DEF VASCULAR VWD CONN. TISS. DSE ITP INFECTIOUS SCURVY EHLER DANLOS SYNDROME DIC DIC THROMBASTHENIAS
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  • 56. Normal hemostasis Vessel injury Collagen exposure TXA2, ADP Platelet aggregation 1  hemostatic plug Stable hemostatic plug Vasoconstriction  blood flow Tissue thromboplastin Blood coag. Fibrin
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  • 61. Prothrombin Time Intrinsic Surface XII Prekallikrein HMW -K XI XIa IX IXa VIIIa Phospoholipid Ca++ Extrinsic VII-VIIa Tissue Factor Phospholipid Ca++ X Xa Va Phospholipid Ca++ Prothrombin(II) Thrombin(IIa) Fibrinogen(I) Fibrin
  • 62. Activated Partial Thromboplastin Time Intrinsic Surface XII Prekallikrein HMW -K XI XIa IX IXa VIIIa Phospoholipid Ca++ Extrinsic VII-VIIa Tissue Factor Phospholipid Ca++ X Xa Va Phospholipid Ca++ Prothrombin(II) Thrombin(IIa) Fibrinogen(I) Fibrin
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  • 74. BLACKFAN-DIAMOND ACQUIRED APLASTIC ANEMIA BONE MARROW FAILURE FANCONI’S ANEMIA CONGENITAL APLASTIC ANEMIA TRANSIENT ERYTHOBLASTOPENIA OF CHILDHOOD (TEC)