(See also Overview of Decreased Erythropoiesis Overview of Decreased Erythropoiesis Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction... read more .)
Congenital pure red cell aplasia (Diamond-Blackfan anemia Perinatal Anemia Anemia is a reduction in red cell mass or hemoglobin and is usually defined as hemoglobin or hematocrit > 2 standard deviations below the mean for age. Some authorities also consider a relative... read more ) 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
Autoimmune disorders Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following types of hypersensitivity reactions may be involved: Type II: Antibody-coated... read more /collagen vascular diseases (systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more
, rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more 
)Medications (eg, tranquilizers, antiseizure medications, recombinant erythropoietin, immune checkpoint inhibitors)
Lymphoproliferative diseases (chronic lymphocytic leukemia Chronic Lymphocytic Leukemia (CLL) Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of phenotypically mature malignant B lymphocytes. Primary sites of disease include peripheral blood, bone marrow... read more , large granular lymphocyte leukemia, chronic myeloid leukemia Chronic Myeloid Leukemia (CML) Chronic myeloid leukemia (CML) occurs when a pluripotent stem cell undergoes malignant transformation and clonal myeloproliferation, leading to a striking overproduction of mature and immature... read more , Hodgkin lymphoma Hodgkin Lymphoma Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more
, non-Hodgkin lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more 
, multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more 
/plasma cell disorders)Parvovirus B19 Erythema Infectiosum (Parvovirus B19 Infection) Erythema infectiosum is caused by acute infection with human parvovirus B19. In children, it causes mild constitutional symptoms and a blotchy or maculopapular rash beginning on the cheeks and... read more
, 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 Myelodysplastic Syndrome (MDS) The myelodysplastic syndrome (MDS) is group of clonal hematopoietic stem cell disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular... read more (1 Diagnosis reference 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... read more ).
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 has been successfully managed with immunosuppressants (eg, prednisone, cyclosporine, cyclophosphamide), especially when an autoimmune mechanism is suspected.
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.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
riboflavin |
No brand name available |
prednisone |
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS |
cyclosporine |
Cequa, Gengraf , Neoral, Restasis, Sandimmune, SangCya, Verkazia |
cyclophosphamide |
Cyclophosphamide, Cytoxan, Neosar |
