Anemia, Acquired Aplastic

Key Features

Essentials of Diagnosis

• Weakness and pallor

• Petechiae, purpura, and bleeding

• Frequent or severe infections

• Pancytopenia with hypocellular bone marrow

General Considerations

• Approximately 50% of cases in childhood are idiopathic

• Other cases are secondary to idiosyncratic reactions to drugs such as phenylbutazone, sulfonamides, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticonvulsants

• Toxic causes include exposure to benzene, insecticides, and heavy metals

• Infectious causes include viral hepatitis, infectious mononucleosis (Epstein-Barr virus [EBV]), and HIV

• Has been associated with human parvovirus B19 infection in immunocompromised children

• Immune mechanisms of marrow suppression are suspected in most cases

Clinical Findings

• Weakness, fatigue, and pallor result from anemia

• Petechiae, purpura, and bleeding occur due to thrombocytopenia

• Fevers due to generalized or localized infections are associated with neutropenia

• Hepatosplenomegaly and significant lymphadenopathy are unusual

Diagnosis

Laboratory Findings

• Usually normocytic, with a low reticulocyte count

• Low WBC count, with a marked neutropenia

• Platelet count is typically below 50,000/μL and is frequently below 20,000/μL

Diagnostic Procedures

• Bone marrow biopsy shows a marked decrease in cellularity, typically < 20% of normal in severe cases

Treatment

• Comprehensive supportive care is essential

• Febrile illnesses require prompt evaluation and usually parenteral antibiotics

• Red blood cell transfusions alleviate symptoms of anemia

• Platelet transfusions

  • May be lifesaving

  • However, should be used sparingly because platelet alloantibodies eventually develop in many patients who then become refractory to platelet transfusions

• Immunomodulation, usually with antithymocyte globulin and cyclosporine or tacrolimus, is associated with a high response rate and improved overall survival. However, incomplete response, relapse, and progression to myelodysplasia/leukemia may occur

• Hematopoietic stem cell transplantation

  • Treatment of choice for severe aplastic anemia when an HLA-identical sibling donor is available

  • Because the likelihood of success with transplant is influenced adversely by receipt of transfusions, HLA typing of family members should be undertaken at the time of diagnosis

• Patients who lack HLA-identical siblings may be able to find matched donors through cord blood banks or the National Marrow Donor Program

Outcome

Complications

• Infection and hemorrhage are the leading causes of death

• Other complications are those associated with therapy

Prognosis

• Children receiving early bone marrow transplant from an HLA-identical sibling have a long-term survival rate > 80%

• Sustained, complete remissions may be seen in 65–80% of patients receiving immunosuppressive therapy

• However, both therapies are associated with an increased risk of myelodysplastic syndromes, acute leukemia, and other malignancies in long-term survivors

References