Diagnostic Considerations
Many symptoms associated with anemia are not caused by diminished RBC mass. For example, ice chewing, calf cramps, and diminished capability to perform muscular work occur in iron deficiency anemia with a hemoglobin (Hb) level of 10-11 g/dL because of depletion of iron-containing proteins other than Hb. [13] Pernicious anemia is often detected incidentally in patients who are asymptomatic despite an Hb level as low as 6 g/dL.
Tolerance of anemia is proportional to the anemia's rate of development. Symptoms and mortality associated with rapidly developing anemia are more profound than in slowly developing anemia.
Differential Diagnoses
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Anemia. Decreased production of red blood cells is suggested in certain patients with anemia. Bone marrow biopsy specimen allows categorization of patients with anemia without evidence of blood loss or hemolysis into 3 groups: aplastic or hypoplastic disorder, hyperplastic disorder, or infiltration disorder. Each category and its associated causes are listed in this image.
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Microcytic anemia.
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Peripheral smear showing classic spherocytes with loss of central pallor in the erythrocytes.
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Bone marrow aspirate containing increased numbers of plasma cells.
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Bone marrow aspirate showing erythroid hyperplasia and many binucleated erythroid precursors.
Tables
Condition |
Serum Iron |
Total Iron-Binding Capacity (TIBC) |
Bone Marrow Iron |
Comment |
Iron deficiency |
↓ |
↑ |
0 |
Responsive to iron therapy |
Chronic inflammation |
↓ |
↓ |
++ |
Unresponsive to iron therapy |
Thalassemia major |
↑ |
N |
++++ |
Reticulocytosis and indirect bilirubinemia |
Thalassemia minor |
N |
N - ↓ |
++ |
Elevation of fetal hemoglobin and Hb A2, target cells, and poikilocytosis |
Lead poisoning |
N |
N |
++ |
Basophilic stippling of RBCs |
Sideroblastic |
↑ |
N |
++++ |
Ring sideroblasts in marrow |
Hemoglobin |
N |
N |
++ |
Hemoglobin electrophoresis |
↓ = decreased; ↑ = increased; 0 = absent; +'s indicate the amount of stainable iron in bone marrow specimens, on a scale of 0-4; N = normal. |
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Megaloblastic bone marrow |
Deficiency of vitamin B12 |
Deficiency of folic acid |
|
Drugs affecting deoxyribonucleic acid (DNA) synthesis |
|
Inherited disorders of DNA synthesis |
|
Nonmegaloblastic bone marrow |
Liver disease |
Hypothyroidism and hypopituitarism |
|
Accelerated erythropoiesis (reticulocytes) |
|
Hypoplastic and aplastic anemia |
|
Infiltrated bone marrow |
Macrocyte |
Larger than normal (> 8.5 µm diameter). See Table 2. |
Microcyte |
Smaller than normal (< 7 µm diameter). See Table 1. |
Hypochromic |
Less hemoglobin in cell. Enlarged area of central pallor. See Table 1. |
Spherocyte |
Loss of central pallor, stains more densely, often microcytic. Hereditary spherocytosis and certain acquired hemolytic anemias |
Target cell |
Hypochromic with central "target" of hemoglobin. Liver disease, thalassemia, hemoglobin D, and postsplenectomy |
Leptocyte |
Hypochromic cell with a normal diameter and decreased MCV. Thalassemia |
Elliptocyte |
Oval to cigar shaped. Hereditary elliptocytosis, certain anemias (particularly vitamin B12 and folate deficiency) |
Schistocyte |
Fragmented helmet- or triangular-shaped RBCs. Microangiopathic anemia, artificial heart valves, uremia, and malignant hypertension |
Stomatocyte |
Slitlike area of central pallor in erythrocyte. Liver disease, acute alcoholism, malignancies, hereditary stomatocytosis, and artifact |
Tear-shaped RBCs |
Drop-shaped erythrocyte, often microcytic. Myelofibrosis and infiltration of marrow with tumor. Thalassemia |
Acanthocyte |
Five to 10 spicules of various lengths and at irregular intervals on surface of RBCs |
Echinocyte |
Evenly distributed spicules on surface of RBCs, usually 10-30. Uremia, peptic ulcer, gastric carcinoma, pyruvic kinase deficiency, and preparative artifact |
Sickle cell |
Elongated cell with pointed ends. Hemoglobin S and certain types of hemoglobin C and l |
|
Hereditary |
Acquired |
Intracorpuscular defect |
Hereditary spherocytosis Hereditary elliptocytosis Hemoglobinopathies Thalassemias Congenital dyserythropoietic anemias Hereditary RBC enzymatic deficiencies Rarer hereditary abnormalities |
Vitamin B12 and folic acid deficiency Paroxysmal nocturnal hemoglobinuria Severe iron deficiency |
Extracorpuscular defect |
|
Physical agents: Burns, cold exposure Traumatic: Prosthetic heart valves, march hemoglobinuria, disseminated intravascular coagulation (DIC), graft rejection Chemicals: Drugs and venoms Infectious agents: Malaria, toxoplasmosis, mononucleosis, hepatitis, primary atypical pneumonia, clostridial infections, bartonellosis, leishmaniasis Hepatic and renal disease Collagen vascular disease Malignancies: Particularly hematologic neoplasia Transfusion of incompatible blood Hemolytic disease of the newborn Cold hemagglutinin disease Autoimmune hemolytic anemia Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) |
