Clinical Review

Aplastic Anemia: Diagnosis and Treatment



From the Oregon Health and Science University, Portland, OR.


  • Objective: To describe the current approach to diagnosis and treatment of aplastic anemia.
  • Methods: Review of the literature.
  • Results: Aplastic anemia can be acquired or associated with an inherited marrow failure syndrome (IMFS), and the treatment and prognosis vary dramatically between these 2 etiologies. Patients may present along a spectrum, ranging from being asymptomatic with incidental findings on peripheral blood testing to life-threatening neutropenic infections or bleeding. Workup and diagnosis involves investigating IMFSs and ruling out malignant or infectious etiologies for pancytopenia.
  • Conclusion: Treatment outcomes are excellent with modern supportive care and the current approach to allogeneic transplantation, and therefore referral to a bone marrow transplant program to evaluate for early transplantation is the new standard of care for aplastic anemia.

Keywords: inherited marrow failure syndrome; Fanconi anemia; immunosuppression; transplant; stem cell.

Aplastic anemia is a clinical and pathological entity of bone marrow failure that causes progressive loss of hematopoietic progenitor stem cells (HPSC), resulting in pancytopenia.1 Patients may present along a spectrum, ranging from being asymptomatic with incidental findings on peripheral blood testing to having life-threatening neutropenic infections or bleeding. Aplastic anemia results from either inherited or acquired causes, and the pathophysiology and treatment approach vary significantly between these 2 causes. Therefore, recognition of inherited marrow failure diseases, such as Fanconi anemia and telomere biology disorders, is critical to establishing the management plan.


Aplastic anemia is a rare disorder, with an incidence of approximately 1.5 to 7 cases per million individuals per year.2,3 A recent Scandinavian study reported that the incidence of aplastic anemia among the Swedish population is 2.3 cases per million individuals per year, with a median age at diagnosis of 60 years and a slight female predominance (52% versus 48%, respectively).2 This data is congruent with prior observations made in Barcelona, where the incidence was 2.34 cases per million individuals per year, albeit with a slightly higher incidence in males compared to females (2.54 versus 2.16, respectively).4 The incidence of aplastic anemia varies globally, with a disproportionate increase in incidence seen among Asian populations, with rates as high as 8.8 per million individuals per year.3-5 This variation in incidence in Asia versus other countries has not been well explained. There appears to be a bimodal distribution, with incidence peaks seen in young adults and in older adults.2,3,6


Acquired Aplastic Anemia

The leading hypothesis as to the cause of most cases of acquired aplastic anemia is that a dysregulated immune system destroys HPSCs. Inciting etiologies implicated in the development of acquired aplastic anemia include pregnancy, infection, medications, and exposure to certain chemicals, such as benzene.1,7 The historical understanding of acquired aplastic anemia implicates cytotoxic T-lymphocyte–mediated destruction of CD34+ hematopoietic stem cells.1,8,9 This hypothesis served as the basis for treatment of acquired aplastic anemia with immunosuppressive therapy, predominantly anti-thymocyte globulin (ATG) combined with cyclosporine A.1,8 More recent work has focused on cytokine interactions, particularly the suppressive role of interferon (IFN)-γ on hematopoietic stem cells independent of T-lymphocyte–mediated destruction, which has been demonstrated in a murine model.8 The interaction of IFN-γ with the hematopoietic stem cell pool is dynamic. IFN-γ levels are elevated during an acute inflammatory response, such as a viral infection, providing further basis for the immune-mediated nature of the acquired disease.10 Specifically, in vitro studies suggest the effects of IFN-γ on HPSC may be secondary to interruption of thrombopoietin and its respective signaling pathways, which play a key role in hematopoietic stem cell renewal.11 Eltrombopag, a thrombopoietin receptor antagonist, has shown promise in the treatment of refractory aplastic anemia, with studies indicating that its effectiveness is independent of IFN-γ levels.11,12


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