Mrs. A is a 48-year-old white woman who has had 2 months of fatigue due to anemia.
|What is the differential diagnosis of anemia? How would you frame the differential?|
The framework for organizing the differential diagnosis of anemia is a combination of pathophysiologic and morphologic. The first step in determining the cause of an anemia is to determine the general mechanism of the anemia, using a pathophysiologic framework. Anemia is caused by 1 of 3 processes:
Acute or chronic blood loss is clinically obvious. Chronic blood loss leads to iron deficiency and consequent underproduction.
Underproduction of RBCs by the bone marrow.
Increased destruction of RBCs, known as hemolysis.
After determining the general mechanism, the next step is to determine the cause of the underproduction or increased destruction. (This chapter will not discuss the approach to acute blood loss.) The framework for underproduction anemia is morphologic:
Microcytic anemias (mean corpuscular volume [MCV] < 80 mcm3)
Anemia of inflammation (formerly called anemia of chronic disease)
Macrocytic anemias (MCV > 100 mcm3)
Megaloblastic anemias (due to abnormalities in DNA synthesis; hypersegmented neutrophils also occur)
Vitamin B12 deficiency
Antimetabolite drugs, such as methotrexate or zidovudine
Nonmegaloblastic anemias (no hypersegmented neutrophils)
Anemia of inflammation
Early iron deficiency
Infiltration of bone marrow due to malignancy or granulomas
Suppression by parvovirus B19 or medications
The framework for hemolytic anemias is pathophysiologic:
Enzyme defects, such as pyruvate kinase or glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hemoglobinopathies, such as sickle cell anemia
RBC membrane abnormalities, such as spherocytosis
Autoimmune: warm IgG, cold IgM, cold IgG
Drug induced: autoimmune or hapten
Macrovascular: shearing due to prosthetic valves
Microvascular: disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS)
Infections, such as malaria
Toxins, such as snake venom and aniline dyes
Paroxysmal nocturnal hemoglobinuria
Figure 6–1 outlines the approach to evaluating anemia caused by underproduction and increased destruction of RBCs.
Mrs. A has a past medical history of obesity, reflux, depression, asthma, and arthritis. She comes to your office complaining of feeling down with progressive fatigue for the last 2 months. She has no chest pain, cough, fever, weight loss, or edema. Her only GI symptoms are poor appetite and her usual reflux symptoms; she has had no vomiting, melena, or rectal bleeding. She still has regular menses that are occasionally heavy. She brought in her medication bottles, which include ranitidine, sertraline, tramadol, cetirizine, and a fluticasone inhaler. Her physical exam shows a depressed affect, clear lungs, a normal cardiac exam, a nontender abdomen, guaiac-negative stool, no edema, and no pallor.
How reliable is the history ...