Classification of Anemia

      Pathogenesis

• Megaloblastic Anemias
• Nonmegaloblastic Macrocytic Anemia
• Relative Incidence

      Laboratory Evaluation

• Hematologic Findings
• Vitamin B₁₂ and Folate Levels in Serum and Erythrocytes
• The Deoxyuridine (dU) Suppression Test
• Serum and Urinary Metabolites
• Therapeutic Trial
• Tests of Vitamin B₁₂ Absorption
• Intrinsic Factor-Blocking Antibodies

      Pathogenesis

• Disorders of the Iron Pathway
• Disorders of Globin Synthesis
• Sideroblastic Anemias

      Laboratory Evaluation

• Hematologic Observations
• Iron Metabolism
• Sideroblasts and Siderocytes
• Erythrocyte Zinc Protoporphyrin
• Globin

      Diagnostic Approach

• Traditional Strategy
• Alternative Strategies

      Classification and Diagnostic Approach

Lab. tests:
CBC with smear & reticulocyte count.

RDW
Coulter instruments calculate the coefficient of variation (CV) in red cell volume and reports it as red cell distribution width (RDW). The upper limit of normal values for RDW is 14.6% .  An increased RDW value is an early and pronounced finding in iron deficiency and most megaloblastic anemias but not in heterozygous thalassemia. In iron deficiency, the RDW value may become abnormal even before the MCV falls below the lower limits of normal.

Blood iron, vit. B12, or folate levels to check for deficiency.

Hemoglobin electrophoresis to check for inherited hemoglobinopathy.

Direct Coombs' (antiglobulin) test - to check for autoimmune hemolytic anemia;  when both direct & indirect Coombs' tests are positive, immune-mediated destruction of RBS is occurring.  In the majority of cases with positive direct but negative indirect Coombs' test, the immune-mediated destruction of RBs is absent.

Osmotic fragility test is abnormal in spherocytosis.

Sugar water test is positive in paroxysmal nocturnal hemoglobinuria (PNH) or AIHA.

Bone marrow study.

If MCV is < 70:  blood iron level, TIBC, % sat, or ferritin; Hemoglobin electrophoresis to check for Beta Thalassemia.
If MCV is > 106: blood Vit. B12 or folate levels; ? liver disease anemia, ? myelodysplasia (blood smear with bilobed & hypogranular neutrophiles; bone marrow with megaloblastoid late, erythroid cells), ? antimetabolic medications as hydroxyurea or mercaptopurine, ? cold agglutinins.

Diminished Production of Mature Erythrocytes (RBC)

Deficiencies:

• Iron deficiency
• Vitamin B12 (cobalamine), or Folate Deficiency
• Erythropoietin deficiency, as in chronic renal failure or chronic inflammation disorders.
• Other deficiency

Replacement of Bone Marrow with Other Cells

• Myelodysplasia
• Multiple myeloma
• Cancer
• Lymphoma
• Other infiltration

Humoral or Cellular Inhibition of normal Cells

• Antibodies
• Toxic chemicals
• Cytokines
• Undefined toxic effects

Accelerated Loss of Mature Erythrocytes (RBC) from the Circulation

• Inherited erythrocyte defects: sickle cell anemia, congenital spherocytosis, Thalassemia
• Acquired erythrocyte defects
• Chemical destruction of erythrocytes
• Antibody-mediated destruction of erythrocytes
• Hemorrhage

Ref:

Lee: Wintrobe's Clinical Hematology, 10th ed., Copyright © 1999

2007

Erythropoiesis-Stimulating Agents (ESA)

1.  Procrit /Epogen (Epoetin alfa)

• anemia, CRF-associated:  12.5-525 units/kg SC/IV 3x/wk Start: 50-100 units/kg SC/IV 3x/wk; Info: IV route preferred for HD pts; recommended target Hgb 10-12 g/dL; decr. dose 25% if Hgb approaches 12 g/dL or incr. 1 g/dL over 2wk; if inadequate response after 8wk, incr. dose 25% q4-8wk
• anemia, chemo-related: 40,000-60,000 units SC qwk Start: 40,000 units SC qwk, incr. dose in 4wk to 60,000 units qwk if Hgb incr. <1 g/dL; Alt: 150 units/kg SC/IV 3x/wk; incr. dose in 8wk to 300 units/kg 3x/wk if inadequate response; Info: recommended target Hgb 10-12 g/dL; decr. dose 25% if Hgb approaches 12 g/dL or incr. 1 g/dL over 2wk; hold dose and restart at 75% dose if Hgb >13 g/dL

2.  Aranesp (Darbepoetin alfa)

• de novo use Start: 0.45 mcg/kg SC/IV qwk; Info: IV route preferred for HD pts; recommended max target Hgb 12 g/dL; incr. dose 25% if Hgb response <1 g/dL/4wk; decr. dose 25% if Hgb response >1 g/dL/2wk; some pts may need q2wk schedule
• conversion from epoetin Start: see pkg. insert for dose based on current epoetin tx, admin SC/IV q1-2wk; Info: IV route preferred for HD pts; recommended max target Hgb 12 g/dL; incr. dose 25% if Hgb response <1 g/dL/4wk; decr. dose 25% if Hgb response >1 g/dL/2wk