bubble_chart Overview

Pure red cell aplasia (PRCA) is a rare syndrome caused by selective aplasia of the erythroid series in the bone marrow. Over 100 cases have been reported in domestic literature. The pathogenesis is mostly related to autoimmunity. Clinically, it can be divided into congenital and acquired categories. The acquired type can be further classified into primary and secondary based on etiology, and into acute and chronic forms based on disease course.

bubble_chart Clinical Manifestations

The common clinical manifestations of this condition include progressive and severe anemia, presenting as normocytic or grade I macrocytic anemia, accompanied by a significant reduction or absence of reticulocytes. Peripheral blood white blood cell and platelet counts are normal or near normal. Bone marrow nucleated cells are not reduced, with normal proliferation of granulocyte and megakaryocyte series, but a marked reduction or complete absence of erythroblast series. In some cases, maturation arrest of the erythroblast series may be observed at an early stage, with small clusters of proerythroblasts and megaloblastoid changes, but more mature erythroblasts are absent. Iron kinetic studies indicate that the underlying issue is impaired erythropoiesis.

(1) **Congenital Pure Red Cell Aplasia (Diamond-Blackfan Anemia)**: 90% of cases manifest between birth and 1 year of age, rarely after 2 years. The inheritance pattern remains unclear, but it is familial. Affected children exhibit delayed growth and development. A few may also present with grade I congenital malformations, such as thumb deformities. Unlike Fanconi anemia, it is rarely associated with malignant diseases. Patients not only have a quantitative deficiency of erythroid progenitor cells but also qualitative abnormalities. Increased HbF, persistence of fetal membrane antigen i, and elevated activity of enzymes in the purine salvage pathway suggest defects in nucleic acid synthesis. Lymphocytes from these patients can inhibit the growth of normal erythroid progenitor cells in vitro. Spontaneous remission occurs in 20% of cases, and 60% respond to adrenal corticosteroids. For non-responders, bone marrow transplantation may be considered.

(2) **Acquired Acute Pure Red Cell Aplasia**: During the course of chronic hemolytic anemia, viral infections—particularly human parvovirus B₁₉ infection—can selectively suppress erythroid progenitor cells, leading to acute pure red cell aplasia, also known as aplastic crisis of hemolytic anemia. In some cases, temporary hematopoietic arrest occurs after viral infection, resulting in pancytopenia and the appearance of giant proerythroblasts in the bone marrow, termed acute hematopoietic arrest. Acute pure red cell aplasia can also occur in children aged 1–4 years, resolving spontaneously within weeks without an infectious cause, known as transient erythroblastopenia of childhood. It may also arise following viral hepatitis or drug induction (e.g., phenytoin, azathioprine, chloramphenicol, isoniazid, procainamide). Most cases recover completely after discontinuation of the offending agent.

(3) **Chronic Acquired Pure Red Cell Aplasia**: Primarily seen in adults, 50% of patients have thymomas, though only 5% of thymoma patients develop pure red cell aplasia. Most thymomas are benign (70% spindle cell type), with a few being malignant. It is more common in women (female-to-male ratio 3–4.5:1). A minority of cases may be secondary to autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis) or certain tumors (e.g., chronic lymphocytic leukemia, chronic myeloid leukemia, lymphoma, immunoblastic lymphadenopathy, biliary adenocarcinoma, stony goiter [thyroid carcinoma], bronchogenic lung cancer, breast cancer). Idiopathic cases are termed primary acquired pure red cell aplasia, caused by various immune mechanisms that inhibit erythroblast production. Patient sera may contain anti-erythroblast antibodies, anti-erythropoietin antibodies, or inhibitory T lymphocytes. Patients often exhibit immunological abnormalities such as elevated or reduced immunoglobulins, monoclonal gammopathy, and positive serum antibodies (e.g., cold agglutinins, cold hemolysins, heterophile antibodies, antinuclear antibodies). Positive Coombs test may also be observed. Some patients may have multiple endocrine gland deficiencies. Pure red cell aplasia without thymoma is more common in men (male-to-female ratio 2:1).

bubble_chart Diagnosis

All patients with the chronic type should undergo thorough examinations to check for thymoma. It is essential to perform posteroanterior, lateral, and 20-degree oblique chest X-rays, which can detect 85–90% of thymomas. The detection rate of CT scans can reach 100%.

bubble_chart Treatment Measures

Once the diagnosis of thymoma is confirmed, it should be surgically removed as early as possible, with a postoperative anemia remission rate of up to 30%. For those who achieve remission after surgery, administration of adrenal corticosteroids or immunosuppressants may be effective.

For primary acquired pure red cell aplasia without thymoma, a combination of adrenal corticosteroids, androgens, and Root Leaf or Flower of Common Threewingnut glycosides can be used to improve efficacy. If treatment is ineffective, immunosuppressants such as azathioprine, cyclophosphamide, 6-mercaptopurine, antilymphocyte globulin, or antithymocyte globulin should be promptly selected, and cyclosporine A may also be considered. Some suggest that high-dose immunoglobulin combined with cyclosporine A can enhance therapeutic outcomes. Effective treatment often leads to reticulocytosis within 1 to 8 weeks. Immunosuppressive therapy can achieve remission in over 66% of patients, but the relapse rate may reach 80%. If all treatments fail, splenectomy may be performed, which is effective in some cases. For those who do not respond to surgery, subsequent immunosuppressive therapy may still be beneficial. For patients with high antibody titers, plasmapheresis can also be considered, and danazol may be tried as well. To alleviate symptoms, red blood cell transfusions can be administered. However, for patients requiring long-term repeated transfusions, the incidence of secondary hemochromatosis is relatively high, and timely use of deferoxamine is recommended.