This patient should undergo an osmotic fragility test. She most likely has hereditary spherocytosis. Inheritance is usually autosomal dominant with variable penetrance but may occasionally be sporadic. Alternations in membrane structure destabilize the erythrocyte, leading to a spherocytic shape, reduced deformability, trapping, and subsequent destruction in the spleen. Hereditary spherocytosis should be suspected in patients with a personal or family history of anemia, jaundice, splenomegaly, or gallstones. Some patients, such as this patient, may come to medical attention because of an aplastic crisis precipitated by an acute parvovirus B19 infection. Spherocytes are present on the peripheral blood smear, and the direct antiglobulin (Coombs) test (DAT) is negative. The osmotic fragility test with 24-hour incubation is a key step in diagnosis, demonstrating increased erythrocyte fragility in hypotonic saline compared with control erythrocytes.
Patients with warm autoimmune hemolytic anemia (WAIHA) may present with rapid or insidious symptoms of anemia or jaundice; mild splenomegaly is often present. Spherocytes are seen on the peripheral blood smear. The DAT is used to diagnose WAIHA. In less than 10% of patients, the DAT may be normal, in which case more sensitive diagnostic testing through a reference laboratory or blood center is required. First-line therapy for WAIHA is glucocorticoids; however, a trial period of prednisone is not indicated in this patient with a negative DAT and a family history of anemia.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal progenitor cell disorder characterized by hemolytic anemia, pancytopenia, or unprovoked thrombosis. Diagnosis is based on flow cytometry results, which can detect CD55 and CD59 deficiency on the surface of peripheral erythrocytes or leukocytes. In the absence of pancytopenia and a history of thrombosis, flow cytometry is not indicated in this patient
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by various mutations on the X chromosome and occurs more commonly in men, often in blacks. During an acute hemolytic episode, bite cells may be seen on the peripheral blood smear, and a brilliant cresyl blue stain may reveal Heinz bodies (denatured oxidized hemoglobin). These findings are not present in the patient's peripheral blood smear, so measuring the G6PD activity is not indicated.
