A 69-year-old man with a history of an Escherichia coli urinary tract infection treated 8 days ago with ceftriaxone presents to the emergency room with symptoms of fatigue and jaundice. Physical examination reveals pallor and icteric sclerae. Laboratory evaluation reveals a hemoglobin level of 7.9 g/dL, elevated lactate dehydrogenase (LDH), low haptoglobin, indirect hyperbilirubinemia, and reticulocytosis. Review of the peripheral smear shows increased reticulocytes, anisocytosis, and spherocytic red blood cells (RBCs). A direct antiglobulin test (DAT) is positive for IgG. The patient is managed with supportive measures and recovers spontaneously after 7 days.
Production of RBCs requires the interaction of several elements and catalysts, including functional bone marrow, erythropoietin, iron, vitamins, and cytokines; deficiency in any of these can lead to anemia.
A systematic approach in narrowing down the cause of anemia should be taken to ensure an accurate diagnosis and avoid unnecessary testing.
In approaching a patient with anemia, the initial work-up should delineate whether the cause is a result of marrow underproduction or peripheral destruction or sequestration. This should be followed by a focused work-up of the suspected cause. Apparent or occult blood loss should be excluded, after which the pathogenesis can be categorized as follows.
Microcytic RBCs: disorders in heme or globin synthesis (eg, iron deficiency, congenital sideroblastic anemia, thalassemia)
Normocytic RBCs: anemia of chronic disease (can be microcytic), chronic kidney disease, or compound deficiencies (eg, iron and folate deficiency)
Macrocytic RBCs: deficiency of vitamin B12 or folate, or liver disease
Anemia secondary to increased RBC destruction (hemolytic anemia)
Intravascular hemolysis: hemoglobinemia, hemoglobinuria, hemosiderinuria, decreased haptoglobin, or elevated LDH2
Extravascular hemolysis (spleen, liver): no release of hemoglobin in the blood; no hemoglobinemia, no hemoglobinuria, no or minimal consumption of haptoglobin, and LDH can be normal
See Table below