Bone marrow - nonneoplastic
Alterations in cellularity
Aplastic anemia (AA)

Topic Completed: 1 May 2013

Revised: 12 July 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Bone marrow [title] aplastic anemia [title] AA

Dragos C. Luca, M.D.
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Cite this page: Luca DC. Aplastic anemia (AA). website. Accessed December 13th, 2019.
Definition / general
  • Multiple cytopenias with trilineage bone marrow hypoplasia in the absence of neoplasia and reticulin fibrosis, indicating a basic failure to produce normal hematopoietic elements
  • The term may be source of confusion since it is frequently used interchangeably with bone marrow failure or to indicate only idiopathic acquired aplastic anemia
  • Rare; 2 - 6 cases/million; if strictly defined, probably 2 cases/million
  • Either constitutional / congenital or acquired (substantially more common)
  • Most patients are adults or elderly in acquired cases; the congenital ones generally manifest during childhood
  • Multifactorial etiology with numerous possible overlapping pathophysiologic mechanisms
  • Constitutional cases are usually linked to DNA repair defects or other types of chromosomal instability; acquired cases are likely antigen driven
  • May be due to immune mediated destruction of marrow hematopoietic progenitor / stem cells, mediated via Th1 T cells (BMC Genomics 2006;7:263)
  • Progenitor / stem cells are substantially reduced in acquired aplastic anemia (due to apoptosis inducing cytokines produced by cytotoxic T cells)
  • Children may acquire monosomy 7 (Am J Clin Pathol 2006;126:925)
  • Presence of substance P in B cells may predict progression to acute leukemia (J Clin Pathol 2006;59:935)
  • Acquired causes: idiopathic or secondary - due to drugs (carbamazapine and valproic acid, Epilepsia 2006;47:1232), chemicals, viruses, ionizing radiation; may be associated with thymoma, lupus (J Clin Rheumatol 2001;7:377); in children, cases are considered acquired only after excluding other causes; in adults, aplastic anemia is assumed to be acquired
  • Congenital causes: dyskeratosis congenita, Fanconi anemia, Schwachman-Diamond syndrome, TAR syndrome
Clinical features and diagnosis
  • Proposed diagnostic criteria (both I and II must be fulfilled in the absence of neoplasia):
    1. At least 2 of the following CBC findings: granulocytes < 500/μL, platelets < 20,000/μL, corrected reticulocyte count < 20 x 109/L
    2. Bone marrow must be either markedly hypoplastic ( < 25% of NAAC*) or moderately hypoplastic (25 - 50% of NAAC*) with < 30% of cells being hematopoietic (*NAAC = normal age appropriate cellularity)
  • Severity by absolute neutrophil count (ANC): nonsevere ( > 500/μL), severe (200 - 500/μL) and very severe ( < 200/μL)
  • Laboratory: variable cytopenias, usually pancytopenia, normocytic normochromic anemia, inadequate reticulocyte response
Constitutional aplastic anemia
Acquired aplastic anemia
  • Usually immune mediated attack sometimes triggered by exposure to toxins, drugs, infections or radiation
  • In idiopathic cases (majority of acquired AA) the inciting event is not apparent but the immune attack still occurs
  • Persistent aplastic state in most instances (progenitor cell damage)
  • Well documented association with certain viral infections (hepatitis - A, B, C; EBV, HIV, parvovirus), drugs (chloramphenicol) and toxins (benzene)
  • Possible association with paroxysmal nocturnal hemoglobinuria
  • May have clonal anomalies (e.g. trisomy 8)
Case reports
Treatment and prognosis
  • Untreated AA is almost universally fatal within 1 - 2 years
  • Immunosuppressive therapy, bone marrow transplantation
Microscopic (histologic) description
  • In practice, most cases demonstrate profound (5 - 10%) hypocellularity
  • Adipose cells predominate; beware of subcortical samples that could be normally hypocellular with fat predominance
  • Usually severe trilineage hypoplasia; sometimes agranulocytosis or red cell aplasia can precede AA
  • Some dyspoiesis, usually mild, may be identified
  • Nonhematopoietic cellularity represented by macrophages, lymphocytes and plasma cells (the last 2 often in a perivascular distribution)
  • Occasional cases with very prominent lymphoid aggregates or lymphoplasmacytic infiltrates raise the question of lymphoma / leukemia / myeloma
  • Other reported abnormalities: increased mast cells, increased eosinophils, fat necrosis, fibrosis, stromal edema
Microscopic (histologic) images

Images hosted on other servers:

Extreme hypocellularity with residual erythropoiesis

Postchemotherapy; infiltrate is primarily plasma cells

Postchemotherapy: iron stain

Differential diagnosis
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