Pure Red Cell Aplasia

Also see Anemia: General Considerations.

Definition and EtiologyTop

Pure red cell aplasia (PRCA) refers to aplasia of the erythroid lineage leading to severe normocytic (in some cases macrocytic) and normochromic anemia. It may be inherited (Diamond-Blackfan syndrome) or acquired. PRCA is also characterized by severe reticulocytopenia (hypoproliferative), which can help differentiate it from other causes of anemia.

Acquired PRCA is thought to be related to T-cell–mediated erythroid destruction, potentially triggered by several etiologies. These include:

1) Viral infections (parvovirus B19, Epstein-Barr virus, HIV, hepatotropic viruses, cytomegalovirus).

2) Immunologic disorders (thymoma, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, common variable immunodeficiency), status post allogeneic stem cell transplant.

3) Lymphoid malignancies (chronic lymphocytic leukemia, large granular lymphocytic leukemia, marginal zone lymphoma).

4) Treatment with an erythropoiesis-stimulating agent (ESA), recombinant human erythropoietin (rhEPO), or drugs such as phenytoin, carbamazepine, valproate, azathioprine, chloramphenicol, sulfonamides, isoniazid.

Many cases of PRCA are idiopathic. PRCA may precede myelodysplastic syndrome, as it can undergo clonal evolution.

Clinical Features and diagnosisTop

The diagnosis of PRCA is usually established in patients >40 years. Clinical features include severe anemia with low reticulocyte count, normal serum erythropoietin levels, and low bone marrow erythroblast counts (<0.5%). Clinical subtypes include acute transient PRCA (caused by viral infections or drugs) and chronic PRCA (idiopathic, thymoma, systemic lupus erythematosus, rheumatoid arthritis). The presence of leukopenia or thrombocytopenia or a history of thrombosis should raise concern for aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), or both.

The diagnostic workup for PRCA should include medication history. Evaluation for infectious, immunologic, and lymphoproliferative disorders is warranted. Most patients undergo peripheral blood testing with viral serologies, autoimmune antibodies, as well as flowcytometry and T-cell rearrangement testing for the presence of clonal large granular lymphocytes. Nutritional deficiencies including vitamin B12, iron, and folic acid can also result in hypoproliferative anemia and need to be excluded.

In the absence of another etiology, a computed tomography (CT) scan of the thorax for thymoma evaluation is warranted. Bone marrow evaluation is required for definitive morphologic assessment, cytogenetic studies, and exclusion of other conditions such as myelodysplastic syndrome or lymphoid or plasma cell infiltration.

TreatmentTop

Treatment for PRCA typically requires management of the underlying trigger, if present. This frequently leads to the resolution of PRCA.

Specific interventions may include drug discontinuation for suspected medication-associated PRCA, consideration of surgical resection for patients with a thymoma, systemic treatment for hematologic malignancies, and the use of IV immunoglobulin (typically at doses of 2 g/kg divided over 2-5 days) for parvovirus B19–associated PRCA.

In cases of idiopathic or immune-related PRCA, immunosuppressive treatment is used (most frequently with glucocorticoids); this also has a role in the management of patients with Diamond-Blackfan anemia. While effective, glucocorticoids do not always produce a durable response and are thus frequently paired with other immunosuppressants: usually cyclosporine [INN ciclosporin].

Other active agents, administered in a specialized setting, may include cyclophosphamide, high-dose IV immunoglobulin, rituximab, antithymocyte globulin, and alemtuzumab. Patients requiring frequent packed red blood cell transfusions may develop iron overload. Allogeneic stem cell transplant is rarely pursued for PRCA but can be considered in refractory cases.