This patient has Felty syndrome, which is the clinical triad of rheumatoid arthritis (RA), splenomegaly, and neutropenia. Splenomegaly and lymphadenopathy may occur secondary to connective tissue disorders such as RA. The unusual cell seen on the peripheral blood smear is a large granular lymphocyte (LGL). LGLs may be seen in up to 40% of patients with Felty syndrome; they may also be associated with other collagen vascular diseases and autoimmune neutropenia. LGL leukemia may also occur in patients with rheumatoid arthritis. Because patients with Felty syndrome and LGL leukemia tend to share HLA-DR4 positivity, they are thought to be part of the same disease spectrum in which immune system dysfunction leads to expansion of this type of cell. The mechanism of neutropenia in Felty syndrome is considered partially autoimmune (likely related to the process leading to development of LGLs) and partially owing to sequestration associated with splenomegaly. Felty syndrome is the most appropriate diagnosis for this patient because the clinical triad is present. This is a useful syndrome to recognize clinically, because it may lead to an RA diagnosis when articular involvement is less prominent.

Aplastic anemia refers to conditions in which the bone marrow fails to produce blood cells, resulting in a hypocellular bone marrow and pancytopenia. It can be acquired or congenital and may be classified as moderate, severe, or very severe. This patient only has leukopenia, which is not consistent with aplastic anemia.

Autoimmune neutropenia is an acquired abnormality that may be associated with underlying disorders of immune regulation such as systemic lupus erythematosus or may exist in a more isolated form. The degree of neutropenia is generally not severe enough to be linked with frequent infections, and spontaneous remission may occur in patients with the primary form. Antineutrophil antibodies may be detected, although tests for them, which differ from the antineutrophil cytoplasmic antibody tests used to evaluate vasculitis, may not be widely available and have variable sensitivity and specificity. In patients in whom antineutrophil antibodies are not detected, the diagnosis is established by excluding other causes.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal progenitor cell disorder that should be considered in patients presenting with hemolytic anemia, pancytopenia, or unprovoked atypical thrombosis. PNH does not present with isolated leukopenia.