Aplastic anemia: Pathophysiology

Semin Hematol. 2022 Jan;59(1):13-20. doi: 10.1053/j.seminhematol.2021.12.002. Epub 2022 Jan 5.


Bone marrow failure (BMF) syndromes are a heterogeneous group of benign hematological conditions characterized by uni- or multi-lineage marrow and/or peripheral blood cytopenia(s), and can be classified in constitutional or acquired syndromes based on pathophysiology. In inherited diseases, germline mutations occur in the hematopoietic stem and progenitor cell (HSPC) compartment causing a progressive loss of normal hematopoiesis, while in acquired syndromes, HPSC compartment disruption can be caused by an extrinsic direct damage by external cytotoxic agents on the stem cell pool or by an autoimmune attack against HSPCs. Aplastic anemia is an acquired immune-mediated BMF syndrome where marrow disruption is driven by a cytotoxic T cell-mediated autoimmune attack against HSPCs sustained by type I interferons that polarize the immune system toward T helper 1 responses in early phases and then toward T helper 17 and effector memory CD8+ T cell in late stage and severe disease. Cytokines and chemokines also play a crucial role in driving immune responses and HSPC growth inhibition and apoptosis, as described for interferon-γ and tumor necrosis factor α. In this review, we summarize current knowledge on acquired aplastic anemia pathophysiology.

Keywords: aplastic anemia; bone marrow failure; immune system; pathophysiology.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Aplastic* / genetics
  • Bone Marrow / pathology
  • Bone Marrow Failure Disorders
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Syndrome