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A Practical Approach To
Anemia
Minal Barve, MD
September 28, 2006
Objective
 Recognition
 Diagnosis: do not overlook the
primary problem
 Hematological data
 Peripheral smear
 Treatment
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:
 Size and shape
 Hb content
 Polychromatophilia
 Inclusions: Howell-Jolly bodies,
basophilic stippling, malaria
 Rouleau
 WBC
 Platelets
Basic chemistries
 BUN, creatinine
 Bilirubin, icterus = 2.5mg/dl (direct and
indirect)
 LDH, haptoglobin
 Proteins, polyclonal/monoclonal
 Iron/TIBC
 Ferritin
 Folic acid
 Vitamin B12
Urinalysis
 Protein: light chains are not
detected by dipstick
 RBC
 Hemoglobin
Mechanism of anemia
 Blood loss
 Decreased production
 Increased destruction
Most common anemias
 Iron deficiency
 Alpha- thalassemia
 Beta-thalassemia
 Anemia of chronic disease
Other anemias
 Sickle cell disorders
 Autoimmune hemolytic anemias
 Folate and B12 deficiency
 Refractory anemia/MDS
 Aplastic anemia
 Red cell membrane or enzyme
defects
Classification of anemias
 Microcytic
 Normocytic
 Macrocytic
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
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2002;2002:100325
Figure 1. Note the profound central pallor of the hypochromic and microcytic RBC
Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2001;2001:100208
Figure 2. Peripheral smear
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 
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
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
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 Valvular
Prosthesis
TTP
Spur Cells PNH
Immune
Hemolysis
Hereditary
Spherocytosis
Valve Disease DIC
Burr Cells
Intracardiac
Myxomas
Malignant
Hypertension
Target Cells
Bongo
drumming
Adeno CA
Eclampsia
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2002;2002:100344
Figure 4. Low-power view showing dense micro-spherocytes without central pallor
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.
Maslak, P. ASH Image Bank 2002;2002:100394
Figure 2. Peripheral smear from a splenectomized patient with recurrent autoimmune
hemolytic anemia
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
Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2001;2001:100214
Figure 1. Note the dense microspherocytes and the macrocytes with polychromasia
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2002;2002:100344
Figure 5. This patient has hereditary elliptocytosis
Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2001;2001:100248
No Caption Found
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
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.
Lazarchick, J. ASH Image Bank 2002;2002:100507
Figure 1. Peripheral smear from a patient with liver disease and hemolytic anemia
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
Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2001;2001:100226
Figure 1. Note the "bite cells" and the cells with "blisters" and dense cross-bonded
hemoglobin
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
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,
Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2001;2001:100231
No Caption Found
Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2001;2001:100231
Figure 2. Note the hypersegmented neutrophil (7-8 lobes)
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
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
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.
 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 500K
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 92K, LDH 1800
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 252K
 BMP: creatinine 3.4
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 52K,
creatinine 3.2, LDH 4200, bili 2.2
Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.
Schrier, S. ASH Image Bank 2001;2001:100249
Figure 1. Note the fragmented schistocytes, burr cells, and helmet cells
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 86K
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 72K
A Practical Approach To Anemia.ppt

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A Practical Approach To Anemia.ppt

  • 1. A Practical Approach To Anemia Minal Barve, MD September 28, 2006
  • 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. Copyright ©2002 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2002;2002:100325 Figure 1. Note the profound central pallor of the hypochromic and microcytic RBC
  • 13. Copyright ©2001 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2001;2001:100208 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
  • 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 Valvular Prosthesis TTP Spur Cells PNH Immune Hemolysis Hereditary Spherocytosis Valve Disease DIC Burr Cells Intracardiac Myxomas Malignant Hypertension Target Cells Bongo drumming Adeno CA Eclampsia
  • 19. Copyright ©2002 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2002;2002:100344 Figure 4. Low-power view showing dense micro-spherocytes without central pallor
  • 20. Copyright ©2002 American Society of Hematology. Copyright restrictions may apply. Maslak, P. ASH Image Bank 2002;2002:100394 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. Copyright ©2001 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2001;2001:100214 Figure 1. Note the dense microspherocytes and the macrocytes with polychromasia
  • 23. Copyright ©2002 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2002;2002:100344 Figure 5. This patient has hereditary elliptocytosis
  • 24. Copyright ©2001 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2001;2001:100248 No Caption Found
  • 25. 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
  • 26. Copyright ©2002 American Society of Hematology. Copyright restrictions may apply. Lazarchick, J. ASH Image Bank 2002;2002:100507 Figure 1. Peripheral smear from a patient with liver disease and hemolytic anemia
  • 27. 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
  • 28. Copyright ©2001 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2001;2001:100226 Figure 1. Note the "bite cells" and the cells with "blisters" and dense cross-bonded hemoglobin
  • 29. 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.
  • 31. 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,
  • 32. Copyright ©2001 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2001;2001:100231 No Caption Found
  • 33. Copyright ©2001 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2001;2001:100231 Figure 2. Note the hypersegmented neutrophil (7-8 lobes)
  • 34. 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
  • 35. 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
  • 36. 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
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  • 38.
  • 39. 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 500K
  • 40.
  • 41. 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 92K, LDH 1800
  • 42.
  • 43. 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 252K  BMP: creatinine 3.4
  • 44.
  • 45. 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 52K, creatinine 3.2, LDH 4200, bili 2.2
  • 46. Copyright ©2001 American Society of Hematology. Copyright restrictions may apply. Schrier, S. ASH Image Bank 2001;2001:100249 Figure 1. Note the fragmented schistocytes, burr cells, and helmet cells
  • 47. 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 86K
  • 48.
  • 49. 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 72K