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Approach to Anemia - Summary. Approach to Anemia – Case 1 37 year old female patient of Caucasian origin37 year old female patient of Caucasian origin.

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Presentation on theme: "Approach to Anemia - Summary. Approach to Anemia – Case 1 37 year old female patient of Caucasian origin37 year old female patient of Caucasian origin."— Presentation transcript:

1 Approach to Anemia - Summary

2 Approach to Anemia – Case 1 37 year old female patient of Caucasian origin37 year old female patient of Caucasian origin referred to the Emergency Room because of anemia referred to the Emergency Room because of anemia Medical background: generally healthy, normalMedical background: generally healthy, normal diet; during the last week treated with an antibiotic diet; during the last week treated with an antibiotic because of suspected pharyngitis because of suspected pharyngitis Complains of weakness and low-grade feverComplains of weakness and low-grade fever

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

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

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

6 Approach to Anemia – Case 1 Laboratory evaluation - Set II: Laboratory evaluation - Set II: - Reticulocytes – 14% - Reticulocytes – 14% - Corrected reticulocyte count: - Corrected reticulocyte count: /% Retics X (measured to the expected Hb ratio)/ /% Retics X (measured to the expected Hb ratio)/ 14% x 7.9/15 = 7.4% 14% x 7.9/15 = 7.4% - Reticulocyte Production Index (RPI): - Reticulocyte Production Index (RPI): /Corrected reticulocyte count/shift correction factor/ /Corrected reticulocyte count/shift correction factor/ 7.4 / 2 = 3.7 (>2) 7.4 / 2 = 3.7 (>2)

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

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

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

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

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12 Approach to Anemia – Case 1 Laboratory evaluation – Set V: Laboratory evaluation – Set V: - Direct anti-globulin (Coombs) test – IgG +3 - 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 An approach to anemia is based on asking 3 main questions: 1. MCV? 2. Reticulocyte count? (Bone marrow function) 3. Involvement of additional lineages? Approach to Anemia

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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36 Ringed Sideroblast Iron

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

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


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