Acquired pure red blood cell aplasia is a disorder of erythroid precursors that results in an isolated normocytic anemia. White blood cells and platelets are not affected. Symptoms result from anemia and include fatigue, lethargy, decreased exercise tolerance, and pallor. Diagnosis requires demonstration of peripheral normocytic anemia and a normocellular bone marrow biopsy with absence of erythroid precursors. Treatment usually involves treatment of underlying cause and in some cases thymectomy or immunosuppression.
(See also Overview of Decreased Erythropoiesis.)
Congenital pure red cell aplasia (Diamond-Blackfan anemia) is discussed elsewhere.
Etiology of Pure Red Blood Cell Aplasia
Pure red blood cell (RBC) aplasia is most often due to an inappropriate immune response causing suppression of erythropoiesis. Well-known causes include
ABO-mismatched bone marrow transplant
Autoimmune disorders/collagen vascular diseases (systemic lupus erythematosus, rheumatoid arthritis)
Medications (eg, tranquilizers, antiseizure medications, recombinant erythropoietin, immune checkpoint inhibitors)
Lymphoproliferative diseases (chronic lymphocytic leukemia, large granular lymphocyte leukemia, chronic myeloid leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma/plasma cell disorders)
Parvovirus B19, particularly in immunocompromised patients such as those with HIV infection or chronic hemolytic anemias (the parvovirus binds to the blood group P antigen on erythroid precursors and is directly cytotoxic to the cells)
Pregnancy
Solid tumors
Thymomas
Toxins (organic phosphates)
Symptoms of Pure Red Blood Cell Aplasia
Symptoms of pure RBC aplasia are generally mild and relate to the degree of the anemia or to the underlying disorder. The onset of pure red blood cell anemia usually is insidious, often occurring over weeks or months. Symptoms related to anemia include fatigue, lethargy, decreased exercise tolerance, and pallor.
Diagnosis of Pure Red Blood Cell Aplasia
Complete blood count (CBC), reticulocyte count
Bone marrow examination
Peripheral blood smear looking for large granular lymphocytes
Sometimes peripheral blood flow cytometry and T cell gene rearrangement testing
Pure RBC aplasia manifests with a normocytic anemia but normal white blood cell and platelet counts. Reticulocytes are decreased (absolute reticulocyte count < 10,000/microliter, reticulocyte percentage < 1%).
The bone marrow reveals normal cellularity with a maturation arrest at the proerythroblast stage. In parvovirus B19 infection, giant pronormoblasts may be present. Although not widely available, if possible, a marrow burst forming units-erythroid (BFU-E) assay should be obtained to differentiate autoimmune causes of pure red cell aplasia from primary bone marrow disorders such as myelodysplastic syndrome (1).
Chest CT is indicated to evaluate for thymoma in the absence of another identified cause.
Diagnosis reference
1. DeZern AE, Pu J, McDevitt MA, et al: Burst-forming unit–erythroid assays to distinguish cellular bone marrow failure disorders. Exp Hematol 41:808–816, 2013.
Treatment of Pure Red Blood Cell Aplasia
Immunosuppression
Sometimes intravenous immunoglobulin (IVIG) or thymectomy
Some patients undergo spontaneous remission after an ABO-incompatible stem cell transplant, if the causative medication is stopped, or following delivery if pregnancy is the cause.
Pure RBC aplasia secondary to parvovirus infection is treated with intravenous immune globulin.
Thymectomy is done in patients with thymoma-associated pure RBC aplasia; most patients improve but are not always cured and require immunosuppressive agents.
Key Points
Pure red cell aplasia involves isolated erythroid hypoplasia.
Immune-mediated suppression of the erythroid cell line is the most likely cause.
Bone marrow cellularity is normal with an arrest of erythroid maturation causing a normocytic anemia.
Direct treatment of underlying cause with thymectomy, IV immune globulin (IVIG), or immunosuppression.
