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A Practical Approach To Anemia Minal Barve, MD September 28, 2006 A Practical Approach To Anemia Minal Barve, MD September 28, 2006

Objective Recognition ¡ Diagnosis: do not overlook the primary problem ¡ l l ¡ Objective Recognition ¡ Diagnosis: do not overlook the primary problem ¡ l l ¡ Hematological data Peripheral smear Treatment

Hematological CBC: Hb, Hct, RBC, WBC and diff, plts, retic count ¡ MCV: useful Hematological CBC: Hb, Hct, RBC, WBC and diff, plts, retic count ¡ MCV: useful <80, 80 -100, >100 ¡ MCH: not useful ¡ MCHC g/dl if high suggests hereditary spherocytosis ¡ RDW: helpful in ddx of iron deficiency vs thalassemia minor ¡

Peripheral Smear ¡ RBC: l l l Size and shape Hb content Polychromatophilia Inclusions: Peripheral Smear ¡ RBC: l l l Size and shape Hb content Polychromatophilia Inclusions: Howell-Jolly bodies, basophilic stippling, malaria Rouleau WBC ¡ Platelets ¡

Basic chemistries ¡ ¡ ¡ ¡ BUN, creatinine Bilirubin, icterus = 2. 5 mg/dl Basic chemistries ¡ ¡ ¡ ¡ BUN, creatinine Bilirubin, icterus = 2. 5 mg/dl (direct and indirect) LDH, haptoglobin Proteins, polyclonal/monoclonal Iron/TIBC Ferritin Folic acid Vitamin B 12

Urinalysis Protein: light chains are not detected by dipstick ¡ RBC ¡ Hemoglobin ¡ Urinalysis Protein: light chains are not detected by dipstick ¡ RBC ¡ Hemoglobin ¡

Mechanism of anemia Blood loss ¡ Decreased production ¡ Increased destruction ¡ Mechanism of anemia Blood loss ¡ Decreased production ¡ Increased destruction ¡

Most common anemias Iron deficiency ¡ Alpha- thalassemia ¡ Beta-thalassemia ¡ Anemia of chronic Most common anemias Iron deficiency ¡ Alpha- thalassemia ¡ Beta-thalassemia ¡ Anemia of chronic disease ¡

Other anemias Sickle cell disorders ¡ Autoimmune hemolytic anemias ¡ Folate and B 12 Other anemias Sickle cell disorders ¡ Autoimmune hemolytic anemias ¡ Folate and B 12 deficiency ¡ Refractory anemia/MDS ¡ Aplastic anemia ¡ Red cell membrane or enzyme defects ¡

Classification of anemias Microcytic ¡ Normocytic ¡ Macrocytic ¡ Classification of anemias Microcytic ¡ Normocytic ¡ Macrocytic ¡

DDX of Microcytosis Iron deficiency anemia Familial telangiectasia (OWR) idiopathic pulmonary hemosiderosis, PNH - DDX of Microcytosis Iron deficiency anemia Familial telangiectasia (OWR) idiopathic pulmonary hemosiderosis, PNH - thalassemia No simple test, trial of iron therapy - thalassemia Thal minor - elevated Hb A 2 if not iron deficient Anemia of chronic disease MCV 75 -82; inadequate erythropoietin response Hb CC African-American, splenomegaly, mild anemia MCV 65, many target cells Hb EE Southeast Asian, no anemia or minimal anemia. MCV 65 many target cells

Figure 1. Note the profound central pallor of the hypochromic and microcytic RBC Schrier, Figure 1. Note the profound central pallor of the hypochromic and microcytic RBC Schrier, S. ASH Image Bank 2002; 2002: 100325 Copyright © 2002 American Society of Hematology. Copyright restrictions may apply.

Figure 2. Peripheral smear Schrier, S. ASH Image Bank 2001; 2001: 100208 Copyright © Figure 2. Peripheral smear Schrier, S. ASH Image Bank 2001; 2001: 100208 Copyright © 2001 American Society of Hematology. Copyright restrictions may apply.

Lab Test for DDx of Common Microcytic Hypochromic Anemias Iron Deficiency Thalassemia Minor Chronic Lab Test for DDx of Common Microcytic Hypochromic Anemias Iron Deficiency Thalassemia Minor Chronic Disease Scrum Iron N or TIBC N or (< 10%) N or Serum Feritin FEP N % Iron Saturation

Important points in iron therapy Determine the underlying cause ¡ Ferrous sulfate orally, parenteral Important points in iron therapy Determine the underlying cause ¡ Ferrous sulfate orally, parenteral iron IV or IM rarely ¡ Start with one tablet (300 mg-60 mg Fe) daily then bid until Hgb normalizes ¡ Then reduce to one tablet daily for a year to replete iron stores ¡ Grey/black iron stools vs tarry stools ¡ Avoid tea with iron, encourage ¡

Normocytic anemia with a normal or reduced retic count ¡ ¡ ¡ ¡ Anemia Normocytic anemia with a normal or reduced retic count ¡ ¡ ¡ ¡ Anemia of chronic disease (reutilization defect) Megaloblastic anemia with thalassemia or iron deficiency Hypoendocrine states Chronic renal failure AIDS Bone marrow infiltration Myelodysplastic syndromes

Normocytic normochromic anemia with increased reticulocyte count Blood loss anemia ¡ Hemolytic anemia ¡ Normocytic normochromic anemia with increased reticulocyte count Blood loss anemia ¡ Hemolytic anemia ¡

Investigation of Hemolytic Anemia Investigation of Hemolytic Anemia

Figure 4. Low-power view showing dense micro-spherocytes without central pallor Schrier, S. ASH Image Figure 4. Low-power view showing dense micro-spherocytes without central pallor Schrier, S. ASH Image Bank 2002; 2002: 100344 Copyright © 2002 American Society of Hematology. Copyright restrictions may apply.

Figure 2. Peripheral smear from a splenectomized patient with recurrent autoimmune hemolytic anemia Maslak, Figure 2. Peripheral smear from a splenectomized patient with recurrent autoimmune hemolytic anemia Maslak, P. ASH Image Bank 2002; 2002: 100394 Copyright © 2002 American Society of Hematology. Copyright restrictions may apply.

Hemolytic anemias ¡ ¡ Coomb’s test direct negative, indirect positive = delayed transfusion reaction Hemolytic anemias ¡ ¡ Coomb’s test direct negative, indirect positive = delayed transfusion reaction Hereditary spherocytosis l l ¡ Sickle cells l l ¡ Osmotic fragility test: fresh and incubated Autosomal dominant, spectrin decreased, splenectomy Sickledex- solubility screening test for hgb S Cellulose acetate electrophoresis necessary to define AS, SC, S-thal etc Elliptocytes l l Most are not anemic or have compensated hemolytic process 10 -15% have chronic hemolytic anemia

Figure 1. Note the dense microspherocytes and the macrocytes with polychromasia Schrier, S. ASH Figure 1. Note the dense microspherocytes and the macrocytes with polychromasia Schrier, S. ASH Image Bank 2001; 2001: 100214 Copyright © 2001 American Society of Hematology. Copyright restrictions may apply.

Figure 5. This patient has hereditary elliptocytosis Schrier, S. ASH Image Bank 2002; 2002: Figure 5. This patient has hereditary elliptocytosis Schrier, S. ASH Image Bank 2002; 2002: 100344 Copyright © 2002 American Society of Hematology. Copyright restrictions may apply.

No Caption Found Schrier, S. ASH Image Bank 2001; 2001: 100248 Copyright © 2001 No Caption Found Schrier, S. ASH Image Bank 2001; 2001: 100248 Copyright © 2001 American Society of Hematology. Copyright restrictions may apply.

Hemolytic anemias ¡ Acanthocytes l ¡ Burr cells l ¡ Spurr cells- end stage Hemolytic anemias ¡ Acanthocytes l ¡ Burr cells l ¡ Spurr cells- end stage liver diseasefatal prognosis Uremia, PK deficiency Target cells l High degree (30 -100%) Hg CC, Hb EE, Hb SC, S-β-thal

Figure 1. Peripheral smear from a patient with liver disease and hemolytic anemia Lazarchick, Figure 1. Peripheral smear from a patient with liver disease and hemolytic anemia Lazarchick, J. ASH Image Bank 2002; 2002: 100507 Copyright © 2002 American Society of Hematology. Copyright restrictions may apply.

Hemolytic anemias ¡ RBC enzyme defects l l l ¡ G 6 PD deficiency-X Hemolytic anemias ¡ RBC enzyme defects l l l ¡ G 6 PD deficiency-X linked, NSHA, Favism, Spot test Pyruvate kinase and other enzyme defects Autosomal recessive, for most Chronic hemolytic anemia Specific enzyme assays Intravascular hemolysis l l Serum haptoglobin Urine hemosiderin-useful 1 -3 weeks after episode of intravascular hemolysis

Figure 1. Note the Figure 1. Note the "bite cells" and the cells with "blisters" and dense cross-bonded hemoglobin Schrier, S. ASH Image Bank 2001; 2001: 100226 Copyright © 2001 American Society of Hematology. Copyright restrictions may apply.

Hemolytic anemias ¡ Causes of chronic intravascular hemolysis l l ¡ Cardiac abnormalities, usually Hemolytic anemias ¡ Causes of chronic intravascular hemolysis l l ¡ Cardiac abnormalities, usually prosthetic valve PNH- paroxysmal nocturnal hemoglobinuria l l l Sucrose hemolysis test Acid serum hemolysis test (Ham’s test) Flow cytometry for CD 55, CD 59

Macrocytic-normochromic anemia MCV 95 -100 ¡ Chronic liver disease ¡ Hypothyroidism ¡ Drugs- hydrea, Macrocytic-normochromic anemia MCV 95 -100 ¡ Chronic liver disease ¡ Hypothyroidism ¡ Drugs- hydrea, methotrexate etc ¡ Primary bone marrow disorderaplastic anemia, MDS, leukemia, myeloma, etc ¡ BM infiltrative disease-miliary TB, metastatic ca, ¡

No Caption Found Schrier, S. ASH Image Bank 2001; 2001: 100231 Copyright © 2001 No Caption Found Schrier, S. ASH Image Bank 2001; 2001: 100231 Copyright © 2001 American Society of Hematology. Copyright restrictions may apply.

Figure 2. Note the hypersegmented neutrophil (7 -8 lobes) Schrier, S. ASH Image Bank Figure 2. Note the hypersegmented neutrophil (7 -8 lobes) Schrier, S. ASH Image Bank 2001; 2001: 100231 Copyright © 2001 American Society of Hematology. Copyright restrictions may apply.

MCV > 115 fl DDX Folate or B 12 Deficiency Folic Acid Deficiency Peripheral MCV > 115 fl DDX Folate or B 12 Deficiency Folic Acid Deficiency Peripheral smear & BM morphology Same B 12 Deficiency Same Dietary Cause Common, in 3 - Rare, except pure 4 months vegans, 3 -4 yrs Drugs interfering with absorbtion Dilantin, oral contraceptives Omeprazole (Prilosec) No May be present Normal Elevated Neurologic findings Methylmalonic acid level Schilling test Useful for etiology Obtain after Rx

Important Points About Anemia Retic peak occurs 1 week after Rx Fe, B 12, Important Points About Anemia Retic peak occurs 1 week after Rx Fe, B 12, folate Hb/Hct increases to normal in 68 weeks If not, complications 1% reticulocytosis increases MCV (Chronic reticulocytosis) 1 fl High LDH suggests megaloblastic anemia (1000 -3000 U/ml) High MCHC suggests hereditary spherocytosis (or acquired spherocytosis) Bilirubin not over 4 mg/dl with hemolysis Higher values = complications

Case 1 27 yo female with a history of lupus presents with a one Case 1 27 yo female with a history of lupus presents with a one week history of worsening dyspnea on exertion ¡ Reports dark urine ¡ Labs: hgb 8, mcv 101, rdw 19, total bili 1. 9 ¡

Case 2 62 yo white male presents with worsening fatigue for 3 months. ¡ Case 2 62 yo white male presents with worsening fatigue for 3 months. ¡ He reported anginal pain to his PCP and was referred to cardiology and had an abnormal stress test ¡ Underwent cardiac cath which was unremarkable ¡ Labs done post- cath showed a hgb of 6, hct 20, MCV 62, RDW 20, platelets 500 K ¡

Case 3 84 yo female living in an assisted living facility admitted for “failure Case 3 84 yo female living in an assisted living facility admitted for “failure to thrive” ¡ Admission labs: WBC 3. 2 with normal diff, hgb 8. 7, mcv 112, platelets 92 K, LDH 1800 ¡

Case 4 68 yo white female with a 10 year history of poorly controlled Case 4 68 yo white female with a 10 year history of poorly controlled type II DM, HTN, CAD presents for routine follow-up. ¡ CBC: wbc 7. 2 with normal diff, hgb 9. 8, hct 28, mcv 82, rdw 11, platelets 252 K ¡ BMP: creatinine 3. 4 ¡

Case 5 28 yo AAM with a h/o HIV brought to the ER for Case 5 28 yo AAM with a h/o HIV brought to the ER for altered mental status ¡ Found to have a temp of 101. 2 ¡ Labs: wbc 2. 2, ANC 1200, hgb 7. 2, mcv 80, rdw 18, platelets 52 K, creatinine 3. 2, LDH 4200, bili 2. 2 ¡

Figure 1. Note the fragmented schistocytes, burr cells, and helmet cells Schrier, S. ASH Figure 1. Note the fragmented schistocytes, burr cells, and helmet cells Schrier, S. ASH Image Bank 2001; 2001: 100249 Copyright © 2001 American Society of Hematology. Copyright restrictions may apply.

Case 6 55 yo female with metastatic breast cancer reports worsening fatigue for a Case 6 55 yo female with metastatic breast cancer reports worsening fatigue for a few weeks ¡ CBC: wbc 6. 8 with 1% blasts, hgb 9. 1, mcv 102, platelets 86 K ¡

Case 7 ¡ ¡ ¡ 72 yo female with no significant PMH is brought Case 7 ¡ ¡ ¡ 72 yo female with no significant PMH is brought for a routine physical by her daughter She has not seen a doctor in 20 years Daughter notes that mom is increasingly tired and has abdominal distension On exam, patient is pale and has marked splenomegaly CBC: wbc 4. 2, hgb 7, hct 20, mcv 94, platelets 72 K