1. Approach to Anemia - Summary

2. Approach to Anemia – Case 1
37 year old female patient of Caucasian origin
referred to the Emergency Room because of anemia
Medical background: generally healthy, normal
diet; during the last week treated with an antibiotic
because of suspected pharyngitis
Complains of weakness and low-grade fever

3. Approach to Anemia – Case 1
On examination: pallor, slight jaundice; spleen mildly enlarged, soft, tender
No lymphadenopathy, no bleeding tendency, no glossitis
Pulse 100, regular, blood pressure and oxygen saturation normal

4. Approach to Anemia – Case 1
Laboratory evaluation - Set I:
- Hemoglobin – 7.9 gr%
- MCV – 100
- RDW – 17
- WBC – normal
- Platelets - normal

5. Approach to Anemia – Case 1
Interpretation: macrocytic anemia
Differential diagnosis:
- Megaloblastic anemia
- Hemolytic anemia
- Myelodysplastic syndrome/Aplastic anemia
- Other

6. Approach to Anemia – Case 1
Laboratory evaluation - Set II:
- Reticulocytes – 14%
- Corrected reticulocyte count:
/% Retics X (measured to the expected Hb ratio)/
14% x 7.9/15 = 7.4%
- Reticulocyte Production Index (RPI):
/Corrected reticulocyte count/shift correction factor/
7.4 / 2 = (>2)

7. Approach to Anemia – Case 1
Interpretation: hyperproliferative anemia
Differential diagnosis:
- Megaloblastic anemia? No
- Myelodysplastic syndrome/Aplastic anemia? No
- Hemolytic anemia? Yes

8. Approach to Anemia – Case 1
Laboratory evaluation - Set III:
- LDH – high
- Bilirubin – high (unconjugated)
- Haptoglobin – low
Diagnosis confirmed: Hemolytic anemia

9. Approach to Anemia – Case 1
Hemolytic anemia – differential diagnosis:
- Intra-corpuscular (hemoglobinopathy, enzymopathy)
- Red cell membrane (cytoskeleton, PNH, spur cell anemia)
- Extra-corpuscular (hypersplenism, mechanic hemolysis, immune hemolysis, toxic/infectious agents)

10. Approach to Anemia – Case 1
Laboratory evaluation - Set IV:
Blood smear
- Anisocytosis (high RDW)
- Polychromasia (reticulocytosis)
- Spherocytes? - Ellyptocytes?
- Bite cells? Spur cells?
- Schistocytes? - Sickle cells?

12. Approach to Anemia – Case 1
Laboratory evaluation – Set V:
- Direct anti-globulin (Coombs) test – IgG +3

13. Approach to Anemia – Case 1
Summary:
- Mild splenomegaly, fever, jaundice
- Macrocytic anemia
- Reticulocytosis
- Spherocytosis
- Positive direct anti-globulin test
Warm-type immune hemolytic anemia, possibly – drug related

14. Approach to Anemia An approach to anemia is based on asking 3
main questions:
1. MCV?
2. Reticulocyte count? (Bone marrow function)
3. Involvement of additional lineages?

15. Approach to Anemia MCV: - Low: Iron deficiency Thalassemia trait
Chronic disease
Sideroblastic anemia
- Normal: Iron deficiency (early)
Renal failure

16. Approach to Anemia - High: Megaloblastic anemia Hemolytic anemia
MDS / Aplastic anemia
Drug-related
Hypothyroidism
Alcoholism
Liver disease

17. Approach to Anemia Reticulocyte count:
- Adequte (RPI>2): Hemolytic anemias (most)
Acute blood loss
Liver disease
- Inadequate (RPI<2): Iron deficiency
Megaloblastic anemia
Anemia of chronic disease
Bone marrow failure
(malignancy, chemotherapy,
MDS/Aplastic anemia)

18. Approach to Anemia Additional lineage(s) involvement:
- Leukopenia: Malignancy
Chemotherapy
Hypersplenism
Drug-related
Megaloblastic anemia
Aplastic anemia

19. Approach to Anemia - Thrombocytopenia: Malignancy Chemotherapy
Hypersplenism
Drug-related
Megaloblastic anemia
Aplastic anemia
TTP
DIC

20. Approach to Anemia
In addition, blood smear always needs to be carefully assessed:
Schistocytes? Spherocytes?
Target cells? Normoblasts?
Spur cells (acanthocytes)? Burr cells?
Malignant cells (leukemia, lymphoma)?
Malaria parasites? Sickle forms?

21. Anemia With Low MCV and Low Reticulocytes
Iron deficiency
Hereditary defects in hemoglobin synthesis (thalassemia trait)
Defects in heme synthsis (sideroblastic anemia)
Anemia of chronic disease

22. Anemia With Normal MCV and Low Reticulocytes
Early or mild iron deficiency anemia
Chemotherapy
Anemia of chronic disease
Anemia of renal failure

23. Anemia with High MCV and Low Reticulocytes
Megaloblastic anemia
Myelodysplastic syndrome / Aplastic anemia
Drug-related anemia
Hypothyroidism
Alcoholism

24. Anemia with High Reticulocytes
Low MCV:
- Thalassemia Major (some cases)
- Spherocytosis
High MCV:
- Sickle cell anemia
- G-6PD deficiency
- Immune hemolytic anemia
- Malaria infection

25. Anemia with Leukopenia and/or Thrombocytopenia
Low reticulocytes:
- Aplastic anemia/Myelodysplastic syndrome
- Chemotherapy
- Alcoholism
- Megaloblastic anemia
High reticulocytes:
- TTP / DIC
- Hypersplenism

26. Approach to Anemia – Case 2
63 year old male patient presented to your clinic with weakness and anemia; generally healthy, no permanent medications.
On examination: afebrile, normal pulse and blood pressure. No hepatosplenomegaly and lymphadenopathy. Scattered purpura over lower extremities and chest.

27. Approach to Anemia – Case 2
Laboratory evaluation - Set I:

28. Approach to Anemia – Case 2
Interpretation: macrocytic anemia with thrombocytopenia
Differential diagnosis:

29. Approach to Anemia – Case 2
Laboratory evaluation - Set II:

30. Interpretation: High MCV, Low RPI Differential Diagnosis:
Megaloblastic anemia
Myelodysplastic syndrome
Aplastic anemia
Drug-related
Alcoholism

31. Approach to Anemia – Case 2
Laboratory evaluation - Set III:
- B12 and Folate levels
Thorough history taking: alcohol? medications?

32. Approach to Anemia – Case 2
Laboratory evaluation - Set IV:

34. Approach to Anemia – Case 2
Laboratory evaluation - Set V:

36. Ringed
Sideroblast
Iron

37. Approach to Anemia – Case 2
Summary:
- Macrocytic anemia
- Thrombocytopenia
- Low RPI
- Dysplastic maturation (peripheral smear,
bone marrow)
- Normal B12 and Folate levels
Myelodysplastic syndrome

38. Copyright © 2005 Elsevier Inc. (USA) All rights reserved.
Table 29-05
Copyright © 2005 Elsevier Inc. (USA) All rights reserved.