Aplastic anemia (AA)

  • Method:
  • Anticoagulant:
  • Recommendation:
  • Method:
    Cytomorphology
  • Anticoagulant:
    EDTA
  • Recommendation:
    obligatory
  • Method:
    Immunophenotyping
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    facultative
  • Method:
    Chromosome analysis
  • Anticoagulant:
    Heparin
  • Recommendation:
    obligatory
  • Method:
    FISH
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    facultative
  • Method:
    Molecular genetics
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    obligatory

Based on the current guidelines and the current state of research, there are different diagnostic recommendations for patients with aplastic anemia. We have summarized the most important information on classification and diagnostic methods at MLL. In addition, we provide further links on prognosis and therapy in aplastic anemia, so that you can inform yourself in more detail.

Aplastic anemia: Classification

Acquired aplastic anemias (AA) are characterized by bi- or tricytopenias resulting from hypo- or aplasia in the bone marrow. Patients with aplastic anemia typically initially experience benign oligoclonal hematopoiesis due to a reduction in the stem cell pool resulting from immune-mediated pathogenesis, in which autoreactive T cells appear to play a major role. During the pathogenesis of aplastic anemia, the majority of bone marrow cells are replaced by adipocytes (Marsh et al. 2009, Ogawa 2016, Young 2018).

For the diagnosis of aplastic anemia, the exclusion of acquired cytopenias, as well as congenital syndromes with bone marrow insufficiency and hypoplastic myelodysplastic syndromes (MDS) is essential (Marsh et al. 2003, Marsh et al. 2009, Killick et al. 2016). In all cases, diagnostics should include cytomorphology, histology, and cytogenetics from bone marrow.

Aplastic anemia can be classified into the following severity levels:

Table 1: Classification of aplastic anemia (two of three criteria must be met) (Onkopedia Guideline Aplastic Anemia 2018).

(Onkopedia Leitlinie AA 2018).

 

Moderately severe AA

Severe AA

Very severe AA

Neutrophil granulocytes

< 1.0 G/L

< 0.5 G/L

< 0.2 G/L

Thrombocytes

< 50 G/L

< 20 G/L

< 20 G/L

Reticulocytes

< 20 G/L

< 20 G/L

< 20 G/L

To diagnose very severe AA, < 0.2 G/L neutrophil granulocytes must be present and, in addition, hypocellular bone marrow must be present (cellularity < 25% or 25-50% with < 30% hematopoietic cells in the bone marrow) in severe and very severe AA, whereas evidence of hypocellular bone marrow is sufficient to diagnose moderately severe AA (Onkopedia Guideline Aplastic Anemia 2018).

Aplastic anemia: Diagnostics

Aplastic anemia: Prognosis

The risk of leukemic transformation is significantly increased when cytogenetic alterations are detected in chromosome banding analysis (Fig. 1).

Fig. 1: Cumulative probability of leukemic transformation within 5 years in AA with normal versus aberrant karyotype (prepared according to Kim et al. 2010).

Depending on the type of cytogenetic alteration, response to immunosuppressive therapy and prognosis may be worse (-7, complex karyotype, 5q syndrome) or better (+8, -13q) (Maciejewski & Selleri 2004, Kim et al. 2010).

In addition to cytogenetic alterations, molecular aberrations such as mutations in the genes ASXL1 and DNMT3A may also increase the risk of developing MDS or AML (see molecular genetics) (Kulasekararaj et al. 2014).

Aplastic anemia: Therapy

With the help of immunosuppressive therapies (IST), approximately 50% of patients with aplastic anemia achieve remission, with significantly higher response in patients with age ≤ 67 years (p=0.002), coexistence of a PNH clone (p=0.017), and normal karyotype (p=0.024) (Maciejewski & Selleri 2004, Kim et al. 2010). Patients with mutations of the genes PIGA, BCOR and BCORL1 also respond significantly better to IST (Yoshizato et al. 2015, Ogawa 2016). An overview of the therapy structure can be found in the Onkopedia Guideline Aplastic Anemia.

Aplastic anemia: Recommendation

The differentiation of aplastic anemia from hypoplastic MDS is important for prognostic assessment as well as for the choice of therapeutic strategies despite the partially overlapping symptoms (Fig. 2), but morphological analyses are challenging due to the poor cellularity of the bone marrow. Therefore, histologic examination on a sufficiently large bone marrow cylinder (at least 15 mm biopsy length) should necessarily be performed to establish the diagnosis. Indications of clonal evolution in the course of aplastic anemia are an increased blast percentage, hypercellular bone marrow in the presence of recurrent or persistent cytopenia, and the appearance of new cytogenetic or molecular genetic aberrations (Maciejewski & Selleri 2004, Afable et al. 2011).

Fig. 2: Overview of common symptoms in AA and hypoplastic MDS (modeled according to Mufti et al. 2018).

Other differential diagnoses include clonal cytopenia of undetermined significance (CCUS) and paroxysmal nocturnal hemoglobinuria (PNH).

Status: July 2022

You may also be interested in

Career

As a rapidly growing, innovative medical laboratory, we are always looking for bright minds to help us bring new and more effective therapies to patients around the world.

Learn more

Services

Do you have questions about sample submission, analyses performed or findings? Here you will find contact details, contact persons and our most frequently asked questions (FAQs).

Learn more

Quality management

We have been certified according to national and international standards since 2009 and have successfully maintained these accreditations.

Learn more