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APPROACH TO A PATIENT WITH ANEMIA Acibadem University Acibadem Medical Faculty Department of Pediatrics Cengiz Canpolat M.D. Professor of Pediatrics Division.

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Presentation on theme: "APPROACH TO A PATIENT WITH ANEMIA Acibadem University Acibadem Medical Faculty Department of Pediatrics Cengiz Canpolat M.D. Professor of Pediatrics Division."— Presentation transcript:


2 APPROACH TO A PATIENT WITH ANEMIA Acibadem University Acibadem Medical Faculty Department of Pediatrics Cengiz Canpolat M.D. Professor of Pediatrics Division of pediatric Hematology-Oncology

3 Objectives Review basic science of the RBC Define Anemia Review key aspects of history, physical and laboratory evaluation Review a systematic approach to the differential diagnosis marrow-basics/

4 Bone Marrow

5 Definitions Anemia is defined as the values of hemoglobin, hematocrit which are more than 2 standard deviations below the mean RBC counts and RBC indices helps us in differential diagnosis

6 RBC-The important players Hemoglobin –reversibly binds and transports oxygen from lungs to tissues –4 globin chains & iron

7 RBC-The important players (2) Iron –key element in the production of hemoglobin –absorption is poor Vitamin B12 Folic acid Zinc

8 General Principles Anemia is a sign, not a disease. Anemias are a dynamic process. Its never normal to be anemic. The diagnosis of iron deficiency anemia mandates further work-up.

9 Differential Diagnosis Classification by Pathophysiology –Blood Loss –Decreased Production –Increased Destruction

10 Blood Loss Acute –Traumatic –Variety of sources Melena, hematemesis, menometrorrhagia Chronic –Occult bleeding Fissura Hemorrhoids Polyps menstruation

11 Decreased Production Infectious Neoplastic Endocrine Nutritional Deficiency Anemia of Chronic Disease

12 Decreased Production INFECTIOUS Bacterial –Tuberculosis Viral –HIV –Parvovirus –CMV

13 Decreased Production NEOPLASTIC Leukemia Lymphoma/solid tm mets Myeloproliferative Syndromes Myelodysplasia

14 Decreased Production ENDOCRINE Thyroid Dysfunction –Hypothyroidism Erythropoietin Deficiency –Renal Failure

15 Decreased Production NUTRITIONAL DEFICIENCY Iron B12 Folate

16 Anemia of chronic disease *Infections: TB, SBE, osteomyelitis, chronic UTI or pyelonephritis, fungal infections *Chronic inflammatory disorders: JRA, SLE, Sarcoidosis, Collagen Vascular Disease, * Malignancy: Metastasis, Leukemia, Lymphoma,

17 Hemolytic Anemias INCREASED DESTRUCTION Hemolytic Anemias Immune Mediated Non-immune Mediated

18 Evaluation of the Patient HISTORY –Is the patient bleeding? Actively? In past? –Is there evidence for increased RBC destruction? –Is the bone marrow suppressed? –Is the patient nutritionally deficient? Pica?

19 Evaluation of the Patient (2) REVIEW OF SYMPTOMS CNS Fatique, Depression, Impaired cognitive function GISAnorexia, Neausia CVSLower skin temperature, Pallor of skin mucous membranes and conjuctivae CRSDyspnea, Tachycardia, Palpitations, Cardiac enlargement/hypertophy, increased pulse pressure, Systolic ejection murmur, Risk of cardiac failure ISImpaired T-cell and Macrophage function GUS Menstrual Problems

20 Evaluation of the Patient (3) PHYSICAL EXAM Stable or Unstable? -ABCs -Vitals Pallor Jaundice / hemolysis Lymphadenopathy Hepatosplenomegally Bony Pain Petechiae Rectal-? Occult blood

21 Red Cell Indices RBCRed Blood Cell HbHemoglobin HctHematocrit MCV Mean Corpuscular Volume MCHMean Corpuscular Hemoglobin MCHCMCH concentration RDWRed Cell Distribution Width

22 Red blood cell Red blood cell indices (RBC), MCH, MCHC, MCV, RDW –Use of volume-sensitive automated blood cell counters, such as the Coulter counter. The red cells pass through a small aperture and generate a signal directly proportional to their volume. – Other automated counters measure red blood cell volume by means of techniques that measure refracted, diffracted, or scattered light

23 Red blood cell Red blood cell indices Automated RBC measurement: –RBC, Hb, MCV Derived RBC indices: –Hct = MCVx RBC x 0.1 –MCH = Hb/RBC x 1 000 000 –MCHC = Hb/Hct x 0.1

24 Laboratory Evaluation Initial Testing –CBC w/ differential (includes RBC indices) –Reticulocyte count –Peripheral blood smear


26 Erythrocyte Development

27 Reticulocytes


29 Reticulocyte count Retic count = % immature RBC Normal 0.5-1.5% (for non-anemic) <1% Inadequate production >=2% Increased production (? adequacy)

30 Laboratory Evaluation (2) Bleeding –Serial HCT or HGB Iron Deficiency –Iron Studies Hemolysis –Serum LDH, indirect bilirubin, haptoglobin, coombs, coagulation studies Bone Marrow Examination Others-directed by clinical indication –hemoglobin electrophoresis –B12/folate levels

31 Differential Diagnosis No 2 Classification by Morphology –Normocytic –Microcytic –Macrocytic


33 Microcytic Anemia MCV <70 Reduced iron availability Reduced heme synthesis Reduced globin production

34 Iron deficiency is a common form of malnutrition that affects more than 2 billion people globally. - Project IDEA (Iron Deficiency Elimination Action)®, CDC

35 Iron defficiency

36 Microcytic Anemia REDUCED IRON AVAILABILTY Iron Deficiency –Deficient Diet/Absorption –Increased Requirements –Blood Loss –Iron Sequestration Anemia of Chronic Disease –Low serum iron, low TIBC, normal serum ferritin –MANY!! Chronic infection, inflammation, cancer, liver disease

37 Iron absorbtion (2) The body absorbs iron best from ingestion of meat (heme-iron pathway) Absorption of iron can be increased by adjunct ingestion of the following: – Absorption of iron can be enhanced by foods high in vitamin C _ Iron absorption can be blocked by coffee, tea, egg yolk, milk, fiber and spinach

38 Microcytic Anemia REDUCED HEME SYNTHESIS Lead poisoning Acquired or congenital sideroblastic anemia Characteristic smear finding ``Basophylic stippling``

39 Sideroblastic Anemias Heterogenous grouping of anemias defined by presence of ringed sideroblasts in the BM Etiologies: –Hereditary (rare), type of porphyria –Myelodysplasia –EtOH –Drugs (INH, Chloramphenicol) Tx: –Trial of pyridoxine for hereditary or INH induced SA

40 Sideroblastic anemia Accumulation of mitochondrial iron in erythroblasts Hereditary Drugs - INH, lead, zinc, alcohol, chloramphenicol, cycloserine, plavix Hypothermia Confirm w/ BM Bx


42 Microcytic Anemia REDUCED GLOBIN PRODUCTION Thalassemias Smear Characteristics –Hypochromia –Microcytosis –Target Cells –Tear Drops


44 Thalassemias Genetic defect in hemoglobin synthesis –  synthesis of one of the 2 globin chains (  or  ) –Imbalance of globin chain synthesis leads to depression of hemoglobin production and precipitation of excess globin (toxic) –“Ineffective erythropoiesis” –Ranges in severity from asymptomatic to incompatible with life (hydrops fetalis) –Found in people of African, Asian, and Mediterranean heritage

45 Macrocytic anemia Macro RPI >= 2 Check Occult Blood Loss No Coombs’ test Yes RPI < 2 Check B12 and folate

46 Macrocytic Anemia MCV > 100 Megaloblastic Abnormalities in nucleic acid metabolism –B12, Folate Non-megaloblastic: Abnormal RBC maturation –Myelodysplasia Alcohol, liver disease, hypothryroidism, GIS Ca, chemotherapy/drugs

47 Macrocytic: RPI < 2 B12/Folate B12 LowNormal MMA High MMA Homocysteine Normal Consider Liver, Renal, Thyroid, Alcohol, Chronic dis. Consider Bone Marrow Bx Homocysteine High Folate Low

48 Macrocytic: RPI < 2 Megaloblastic Anemia B12 Inadequate absorption Synthesized by bacteria Meat, fish, dairy (strict vegans) Absorbed as B12-IF complex in ileum (gastrectomy) Ca++ and pH dependant (PPI) Folate Inadequate intake Synthesized by plants and micro- organism Green leafy vege’s Fruits Absorbed in jejunum

49 Macrocytic: RPI < 2 Megaloblastic Anemia Smear Macro-ovalocytic Polychromasia Hypersegmented neutrophil Other Labs Homocysteine – Folate def. Methylmalonic A – B12 def. Intrinsic Factor Ab test – very specific for pernicious anemia but only 50%sensitve Parietal cell AB test – quite sensitive (90%) but not Spesific Schilling test

50 Macrocytic: RPI < 2 Non-megaloblastic Consider Liver, Renal, Endocrine (thyroid), alcohol, drugs Consider anemia of chronic disease Myelodysplastic Myeloproliferative - Leukemia, Lymphoma, Multiple Myeloma Get Bone Marrow Biopsy

51 Macrocytic: RPI < 2 continues Aplastic Anemia Fanconi anemia – congenitalFanconi anemia Direct stem cell destruction – external radiationDirect stem cell destruction Drugs - chloramphenicol, gold, sulfonamides, felbamateDrugs Other Toxins - Solvents, degreasing agents, pesticides Viral infection - parvovirus B19, HIV, otherViral infection Idiopathic

52 Macrocytic: RPI >= 2 Occult Blood Loss? Yes Investigate source No Coombs’ (DAT) Check for Hemolysis Peripheral smear

53 Macrocytic: RPI >= 2 Hemolytic Anemia Other Lab Characteristics RBC morphology Serum haptoglobin Serum LDH Unconjugated bilirubin Hemoglobinuria Hemosiderinuria

54 Macrocytic: RPI >= 2 Hemolytic Anemia Coombs’ (DAT) Positive Immune Hemolysis Drug related Hemolysis Transfusion, Infection, Cancer Negative Hemoglobinopathy, G6PD, PK, Spherocytosis, Eliptocytosis, PNH, TTP, DIC

55 Normocytic Anemia Hyperproliferative (RPI >= 2) Use same flow chart as macrocytic hyperproliferative Occult Blood Loss? Yes Investigate source No Coombs’ (DAT) Check for Hemolysis Peripheral smear

56 Normocytic Anemia Hypoproliferative (RPI < 2) 1. Get iron panel (ferritin)/B12/folate - some clue from RBC indices to check early disease, high RDW, peripheral smear. 2. Consider liver, renal, drugs, toxin, endocrine (thyroid), and anemia of chronic disease. 3. Get BM bx - Leukopenia, thrombocytopenia, CRI < 0.1 - Aplastic anemia/pancytopenia - Abnormal (immature) cells on smear

57 Elliptocytes/ovalocytes Abnormal cytoskeletal proteins Hereditary elliptocytosis

58 Howell Jolly body Nuclear remnant - DNA hemolytic anemia absent or hypofunction spleen

59 Schistocyte/helmet cells Fragmented (mechanical or phagocytosis) DIC TTP HUS Vasculitis prosthetic heart valve severe burns

60 Sickle cells Molecular aggregation of Hgb-S SS, SC, S-thallassemia Rarely S-trait

61 Spherocyte There is an absent central pallor, red cells look smaller Hereditary spherocytosis

62 Stomatocyte Mouth like membrane defects Smear artifact Hereditary stomatocytosis Liver disease



65 Target cells Hemoglobinopathies Thalassemia Liver disease

66 Tear drop cells Smear artifact Myelofibrosis Promyeloblastic leukemia Space occupying lesions of marrow

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