Aplastic anemia is a serious condition defined as pancytopenia with an "empty" bone marrow (hypoplastic or aplastic). The anemia is only one part of the spectrum of sequelae that result from this, and is not as clinically significant as the concomitant neutropenia, lymphopenia and thrombocytopenia. There are an estimated 2-4 million cases per year of aplastic anemia, and the incidence occurs in three peaks: 2-5 years, 20-25 years and 55-60 years. Other causes of pancytopenia include: malignancy (leukemia or other cancer replacing bone marrow), megaloblastic hematopoiesis, viral infection, paroxysmal nocturnal hematuria and myelodysplastic syndrome.

Etiology:

70% of aplastic anemia cases are idiopathic, but other known causes are:

• Hereditary:
• Fanconi anemia
• Dyskeratosis congenital
• Schwachman-Diamond syndrome
• Amegakaryocytic thrombocytopenia
• Acquired:
• Direct stem cell destruction
• Drugs
• Toxic chemicals
• Infection (viral, hepatitis)
• Immune disorders
• Collagen vascular diseases

• Anemia: fatigue and pallor
• Thrombocytopenia: unexplained or excessive bleeding, easy bruising
• Neutropenia: fever, mucosal ulcerations, bacterial infection

Definitive diagnosis is made with bone marrow biopsy, but the workup for pancytopenia should include an evaluation for all possible causes of pancytopenia as well as an investigation into the etiologies of aplastic anemia. These labs include: CBC with platelets and smear, drug screen, viral serologies, serum folate and B12, Fanconi anemia screening, CD 55/59 (for PNH), LFTs. The bone marrow biopsy will commonly show profound hypocellularity, but no malignant infiltrates or fibrosis. The hematopoetic cells that are present will be normal and should not be megaloblastic.

Treatment:

If the patient has been exposed to any agents known to cause aplastic anemia, these should be discontinued or removed. However, in many cases the damage to the bone marrow will be irreversible. Initial treatment should consist of supportive care: transfusions and limiting infectious exposures. Definitive therapy consists of hematopoietic stem cell transplantation, with matched sibling donor transplants having a cure rate of 60-70%, or immunosuppressive therapy. Studies have documented a 50% response rate to antithymocyte globulin or cyclosporine and 75-80% response rate with more intensive, multi-agent therapy. If available with related matched donor, HCT has been shown to improve survival compared with immunosuppressive therapy.

References

1. Doney, K et al, Ann Intern Med 1997; 126:107

2. Young N, and Maciejewski G The Pathophysiology of Acquired Aplastic Anemia NEJM 1999;336:1365-72