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Aplastic Anemia

(Hypoplastic Anemia)

By Alan E. Lichtin, MD, Cleveland Clinic;Cleveland Clinic Lerner College of Medicine

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Aplastic anemia is a normocytic-normochromic anemia that results from a loss of blood cell precursors, causing hypoplasia of bone marrow, RBCs, WBCs, and platelets. Symptoms result from severe anemia, thrombocytopenia (petechiae, bleeding), or leukopenia (infections). Diagnosis requires demonstration of peripheral pancytopenia and the absence of cell precursors in bone marrow. Treatment is equine antithymocyte globulin and cyclosporine. Erythropoietin, granulocyte-macrophage colony-stimulating factor, and bone marrow transplantation may also be useful.

The term aplastic anemia commonly implies a panhypoplasia of the marrow with associated leukopenia and thrombocytopenia. In contrast, pure RBC aplasia is restricted to the erythroid cell line. Although both disorders are uncommon, aplastic anemia is more common.


True aplastic anemia (most common in adolescents and young adults) is idiopathic in about half of cases. Recognized causes are chemicals (eg, benzene, inorganic arsenic), radiation, and drugs (eg, antineoplastic drugs, antibiotics, NSAIDs, anticonvulsants, acetazolamide, gold salts, penicillamine, quinacrine). The mechanism is unknown, but selective (perhaps genetic) hypersensitivity appears to be the basis.

Fanconi anemia is a very rare, familial form of aplastic anemia with bone abnormalities, microcephaly, hypogonadism, and brown pigmentation of skin. It occurs in children with abnormal chromosomes. Fanconi anemia is often inapparent until some illness (especially an acute infection or inflammatory disorder) supervenes, causing peripheral cytopenias. With clearing of the supervening illness, peripheral values return to normal despite reduced marrow mass.

Pure RBC aplasia may be acute and reversible. Acute erythroblastopenia is a brief disappearance of RBC precursors from the bone marrow during various acute viral illnesses (particularly human parvovirus infection), especially in children. The anemia lasts longer than the acute infection. Chronic pure RBC aplasia has been associated with hemolytic disorders, thymomas, and autoimmune mechanisms and, less often, with drugs (eg, tranquilizers, anticonvulsants), toxins (organic phosphates), riboflavin deficiency, and chronic lymphocytic leukemia. A rare congenital form, Diamond-Blackfan anemia, usually occurs during infancy but has also been reported in adulthood. Diamond-Blackfan anemia is associated with bony abnormalities of the thumbs or digits and short stature.

Symptoms and Signs

Although onset of aplastic anemia usually is insidious, often occurring over weeks or months after exposure to a toxin, occasionally it is acute. Signs vary with the severity of the pancytopenia. Symptoms and signs of anemia (eg, pallor) usually are severe.

Severe thrombocytopenia may cause petechiae, ecchymosis, and bleeding from the gums, into the conjunctivae, or other tissues. Agranulocytosis commonly causes life-threatening infections. Splenomegaly is absent unless induced by transfusion hemosiderosis. Symptoms of pure RBC aplasia are generally milder and relate to the degree of the anemia or to the underlying disorder.


  • CBC

  • Bone marrow examination

Aplastic anemia is suspected in patients, particularly young patients, with pancytopenia (eg, WBC < 1500/μL, platelets < 50,000/μL). Pure RBC aplasia (including Diamond-Blackfan anemia) is suspected in patients with bony abnormalities and normocytic anemia but normal WBC and platelet counts. If either diagnosis is suspected, bone marrow examination is done.

In aplastic anemia, RBCs are normochromic-normocytic (sometimes marginally macrocytic). The WBC count reduction occurs chiefly in the granulocytes. Platelets are often far below 50,000/μL. Reticulocytes are decreased or absent. Serum iron is elevated. The bone marrow is acellular. In pure RBC aplasia, normocytic anemia, reticulocytopenia, and elevated serum iron are present, but WBC and platelet counts are normal. Bone marrow cellularity and maturation may be normal except for absence of erythroid precursors.


  • Equine antithymocyte globulin, corticosteroids, and cyclosporine

  • Sometimes hematopoietic cell transplantation

  • Sometimes cytokines

  • Sometimes surgery in thymoma-associated RBC aplasia

In aplastic anemia, treatment of choice is equine antithymocyte globulin (ATG) 10 to 20 mg/kg diluted in 500 mL saline and infused IV over 4 to 6 h once/day for 10 consecutive days. Shorter regimens are also used. About 60% of patients respond to ATG. Allergic reactions and serum sickness may occur; some experts advocate skin testing (to identify allergy to horse serum) and concomitant corticosteroids (prednisone 40 mg/m2 po once/day beginning on day 7 for 10 days or until symptoms subside). Cyclosporine (5 to 10 mg/kg po once/day) is as effective as ATG and produces responses in about 50% of patients who do not respond to ATG, suggesting that its mechanism of action is different. Combined ATG and cyclosporine is also effective. If aplastic anemia is very severe or fails to respond to ATG and cyclosporine, bone marrow transplantation or treatment with cytokines (erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor) may be effective.

Hematopoietic stem cell transplantation may help younger patients (particularly patients < 30) but requires an identical twin or an HLA-compatible sibling. At diagnosis, siblings are evaluated for HLA compatibility. Because transfusions pose a risk to subsequent transplantation, blood products are used only when essential.

Pure RBC aplasia has been successfully managed with immunosuppressants (prednisone, cyclosporine, or cyclophosphamide), especially when an autoimmune mechanism is suspected. Because patients with thymoma-associated pure RBC aplasia improve after thymectomy, CT is used to seek the presence of such a lesion, and surgery is considered.

Key Points

  • Aplastic anemia involves panhypoplasia of the marrow with anemia, leukopenia, and thrombocytopenia.

  • Many cases are idiopathic, but chemicals, drugs, or radiation may be involved.

  • Manifestations including severe pallor and weakness, petechiae, ecchymosis and mucosal bleeding, and severe infection.

  • Bone marrow examination usually is done and shows acellularity.

  • Give equine antithymocyte globulin (ATG) and/or cyclosporine; corticosteroids may be needed to control allergic reactions to ATG.

  • Bone marrow transplantation or treatment with erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor may be needed.

* This is the Professional Version. *