A Practical Approach to Anemia

1. A Practical Approach To Anemia

2. Objective
• Recognition
• Diagnosis: do not overlook the primary
problem
– Hematological data
– Peripheral smear
• Treatment

3. 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

4. Peripheral Smear
• RBC:
– Size and shape
– Hb content
– Polychromatophilia
– Inclusions: Howell-Jolly bodies, basophilic stippling,
malaria
– Rouleau
• WBC
• Platelets

5. Basic chemistries
• BUN, creatinine
• Bilirubin, icterus = 2.5mg/dl (direct and indirect)
• LDH, haptoglobin
• Proteins, polyclonal/monoclonal
• Iron/TIBC
• Ferritin
• Folic acid
• Vitamin B12

6. Urinalysis
• Protein: light chains are not detected by
dipstick
• RBC
• Hemoglobin

7. Mechanism of anemia
• Blood loss
• Decreased production
• Increased destruction

8. Most common anemias
• Iron deficiency
• Alpha- thalassemia
• Beta-thalassemia
• Anemia of chronic disease

9. Other anemias
• Sickle cell disorders
• Autoimmune hemolytic anemias
• Folate and B12 deficiency
• Refractory anemia/MDS
• Aplastic anemia
• Red cell membrane or enzyme defects

10. Classification of anemias
• Microcytic
• Normocytic
• Macrocytic

11. 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 A2 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

12. Figure 1. Note the profound central pallor of the hypochromic and microcytic RBC

13. Figure 2. Peripheral smear

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

15. Important points in iron therapy
• Determine the underlying cause
• Ferrous sulfate orally, parenteral iron IV or IM rarely
• Start with one tablet (300 mg-60mg 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 citrus fruits

16. 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

17. Normocytic normochromic anemia with increased
reticulocyte count
• Blood loss anemia
• Hemolytic anemia

18. Investigation of Hemolytic Anemia
Spherocytes Schistocytes Specific
Morphological
Features
No Specific
Features
Coombs Test Big Vessel
Disease or
Trauma
Small Vessel
Disease
Sickle Cells G6PD
Ellip tocytes PK & other
enzyme defects
Positive Negative Valvul ar
Prosthesis
TTP
Spur Cells PNH
Immune
Hemolysis
Hereditary
Spherocytosis
Valve Disease DIC
Burr Cells
Intracardiac
Myxomas
Malign ant
Hypertension
Target Cells
Bongo
drumming
Adeno CA
Eclampsia

19. Figure 4. Low-power view showing dense micro-spherocytes without central pallor

20. Figure 2. Peripheral smear from a splenectomized patient with recurrent autoimmune
hemolytic anemia

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

22. Figure 1. Note the dense microspherocytes and the macrocytes with polychromasia

23. Figure 5. This patient has hereditary elliptocytosis

24. Hemolytic anemias
• Acanthocytes
– Spurr cells- end stage liver disease- fatal prognosis
• Burr cells
– Uremia, PK deficiency
• Target cells
– High degree (30-100%) Hg CC, Hb EE, Hb SC, S-β-thal

25. Figure 1. Peripheral smear from a patient with liver disease and hemolytic anemia

26. Hemolytic anemias
• RBC enzyme defects
– G6PD 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
– Serum haptoglobin
– Urine hemosiderin-useful 1-3 weeks after episode of intravascular
hemolysis

27. Figure 1. Note the "bite cells" and the cells with "blisters" and dense cross-bonded
hemoglobin

28. Hemolytic anemias
• Causes of chronic intravascular hemolysis
– Cardiac abnormalities, usually prosthetic valve
– PNH
• PNH- paroxysmal nocturnal hemoglobinuria
– Sucrose hemolysis test
– Acid serum hemolysis test (Ham’s test)
– Flow cytometry for CD55, CD59

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

31. Note the hypersegmented neutrophil (7-8 lobes)

32. MCV > 115 fl DDX Folate or B12 Deficiency
Folic Acid
Deficiency
B12 Deficiency
Peripheral smear & BM
morphology
Same Same
Dietary Cause Common, in 3-4
months
Rare, except pure
vegans, 3-4 yrs
Drugs interfering with
absorbtion
Dilantin, oral
contraceptives
Omeprazole (Prilosec)
Neurologic findings No May be present
Methylmalonic acid level Normal Elevated
Schilling test Useful for etiology
Obtain after Rx

33. Important Points About Anemia
Retic peak occurs 1 week after Rx Fe, B12, folate
Hb/Hct increases to normal in 6-8 weeks If not, complications
1% reticulocytosis increases MCV 1fl (Chronic reticulocytosis)
High LDH suggests megaloblastic anemia (1000-3000 U/ml)
High MCHC suggests hereditary
spherocytosis
(or acquired spherocytosis)
Bilirubin not over 4mg/dl with hemolysis Higher values = complications

34. THANK YOU