A Comprehensive Approach to Evaluating Anemia

Productive State • Hyper-productive – Elevated reticulocyte count • Acute blood loss • Replacement of a deficient nutrient • Hemolysis

Lloyd E. Damon, M.D. Professor of Clinical Medicine

• Hypo-productive – Normal or inadequately elevated reticulocyte count • Everything else

Anemia by Cell Size microcytic 100 fL

Size Does Not Answer All Questions microcytic 100 fL

Be aware of mixed anemias!

1

RBC Size Classification • Microcytic – – – –

Iron deficiency Anemia of chronic disease Thalassemia Lead toxicity

Microcytic Anemias Hypo-productive

Hyper-productive

Iron deficiency

Thalassemia*

• Normocytic

Anemia of chronic disease

– Anything but thalassemia

• Macrocytic – Megaloblastic – Non-megaloblastic

Lead toxicity *normal or elevated RBC count

Microcytosis Plus Elevated RBC Count

Macrocytic Anemia

Smear Normal Ferritin

Low Ferritin Diseases

Thalassemia

Polycythemia vera Plus Iron deficiency Thalassemia plus Iron deficiency

Megaloblastic

Non-Megaloblastic

•macroovalocytes •hypersegmented neutrophils Vitamin B12 deficiency Folate deficiency

•target cells •other poikilocytosis

DNA synthesis inhibitors

Cirrhosis Hypothyroidism Hemolysis

2

Iron Metabolism

Anemia of Chronic Disease relative or absolute hypoerythropoietemia* •

Anemia of inflammation** - sideropenia • • • • • • • •

•

‘Anemia’ ’ of endocrine deficiency - euferria • • • •

• Hematology 2010; 276-80

Malignancy Granulomatous disease Autoimmune rheumatologic disorders Chronic infection Hospitalized patient with subacute illness Heart failure Chronic kidney disease Unknown Hypothyroid Panhypopituitarism Hypoadrenalism Hypogonadism (males)

*Geriatrics 1992: 47: 47-57 **Hematology 2010; 276-280

Anemia of visceral organ failure - variable serum iron • Renal failure • Hepatic failure

Reprinted with Permission from the American Society of Hematology

Anemia of Inflammation - Hepcidin and Ferroportin

Anemia of Inflammation • Blunted response to erythropoietin • Shortened RBC survival • Pro-inflammatory cytokines restrict erythropoiesis and sequester iron in splenic macrophages – TNFα α, IL-1β β , macrophage migration inhibitory factor, acute phase reactants

• IL6 mediates hepcidin transcription which promotes the internalization and degradation of ferroportin – Reduced iron absorption across intestinal lumen – Impaired release of iron in macrophages to marrow erythroid progenitors

Hematology 2010: 276-280 Hematology 2010; 276-280 Reprinted with Permission from the American Society of Hematology

3

Iron Deficiency vs ACD Iron deficiency MCV low, normal MCH low, normal serum iron low transferrin normal, high % saturation low ferritin normal, low* sol. transferrin high receptor

ACD

Anemia of Inflammation Inflammation

low, normal low, normal low normal, low low normal, high normal

Iron Deficient

Iron Responsive

Iron Replete

Iron Non-Responsive

*