13-08: Pure Red Cell Aplasia

Acquired pure red cell aplasia is rare. It is an autoimmune disease mediated by T lymphocytes and/or by an IgG antibody against erythroid precursors in the bone marrow. In adults, the disease is usually idiopathic. However, cases have been seen in association with systemic lupus erythematosus, chronic lymphocytic leukemia (CLL), lymphomas, or thymoma. Some medications (phenytoin, chloramphenicol) may cause red cell aplasia. Rarely, anti-erythropoietin antibodies cause pure red cell aplasia in patients who are treated with recombinant erythropoietin. Transient episodes of red cell aplasia are probably common in response to viral infections, especially parvovirus infections. However, these acute episodes will go unrecognized unless the patient has a chronic hemolytic disorder or a chronic immunocompromised state, in which case the hematocrit may fall precipitously.

The only signs are those of anemia unless the patient has an associated autoimmune or lymphoproliferative disorder. The anemia is often severe and normochromic, with low or absent reticulocytes. Red blood cell morphology is normal, and the myeloid and platelet lines are unaffected. The bone marrow is normocellular with markedly reduced or absent erythroid progenitors; all non-erythroid elements are present and normal. The bone marrow karyotype is normal on standard banding cytogenetics. In some cases, chest imaging studies will reveal a thymoma.

The disorder must be distinguished from aplastic anemia (in which the marrow is hypocellular and all cell lines are affected) and from myelodysplasia. This latter disorder is recognized by the presence of morphologic abnormalities that should not be present in pure red cell aplasia.

Possible offending medications should be stopped. Most patients will require red blood cell transfusion support. With thymoma, resection alone results in amelioration of anemia in a low proportion of cases (about 10%). High-dose intravenous immune globulin has produced responses in a small number of cases, mainly during parvovirus infections. For idiopathic cases, the treatment of choice is immunosuppressive therapy with a calcineurin inhibitor (ie, cyclosporine) with durable response rates of 65–87%. A calcineurin inhibitor is usually used in conjunction with surgical resection in cases of thymoma. Monotherapy with corticosteroids produce responses in 30–60% of cases, but relapses are common once corticosteroids are discontinued. Anti-CD20 monoclonal antibody (rituximab) is the treatment of choice in the setting of anti-erythropoietin antibodies. In patients with an associated lymphoproliferative disorder, treating the neoplasm should also treat the anemia.

WHEN TO REFER

All patients should be referred to a hematologist.