Defining the aplastic anemia (AA).
| * criteria for severe and very severe AA.1 | ||
| Abbreviations: FBC; MDS/AML, myelodysplastic syndrome/acute myeloid leukemia; T-LGL, T-cell large granular lymphocytic leukemia; DEB, diepoxybutane; MMC, mitomycin C; EBV, Epstein-Barr virus | ||
| 1. | Traditional definition | Confirmation of diagnosis |
| Pancytopenia* with hypocellular bone marrow (BM), hematopoietic tissue replaced by fat cells, in absence of abnormal infiltrate or increase in reticulin. | Full blood count, reticulocyte count, blood film examination, BM aspirate and trephine | |
| *At least 2 of the following required: Hb < 10 g/dL; platelet count < 100 × 109/L; and neutrophil count < 1.5 × 109/L. | ||
| 2. | Is the diagnosis really AA? | |
| Or is there another cause for pancytopenia and hypocellular BM? | Exclude hypocellular MDS/AML, T-LGL, myelofibrosis, lymphoma, atypical mycobacterial infection, anorexia nervosa | |
| 3. | Is the disease an inherited bone marrow failure syndrome? | Clues in medical history and clinical examination and diagnostic tests: |
| Fanconi anemia | Presence of café au lait spots, short stature, anomalies of upper extremities etc. Increased chromosome breakages of peripheral blood lymphocytes with DEB/MMC | |
| Dyskeratosis congenita | Nail dystrophy, leukoplakia and skin pigmentation, but also pulmonary fibrosis, osteoporosis, liver function abnormality. DKC-1 (X-linked), TERC (autosomal dominant), TERT gene mutation analysis | |
| Shwachmann-Diamond syndrome | History of pancreatic insufficiency, neutropenia prior to AA, short stature. SBDS gene mutation analysis | |
| 4. | What is the etiology? | |
| Idiopathic | 70–80% of cases | |
| Post-hepatitic | Liver function tests, viral studies (hepatitis A, B, C, G, but usually negative, EBV rarely) | |
| Drugs and chemicals | Careful drug and exposure history, but no tests available to prove association | |
| Environmental/occupational exposures | ||
| Paroxysmal nocturnal hemoglobinuria | ||
| Rarely: pregnancy, SLE, thymoma, eosinophilic fasciitis | Flow cytometry of GPI-anchored proteins on red cells, neutrophils and monocytes | |
| 5. | Are abnormal clones present? | |
| Paroxysmal nocturnal hemoglobinuria | Flow cytometry as above | |
| Cytogenetic clone | BM cytogenetics +/− FISH | |
| T-LGL clone | TCR gene analysis and immunophenotyping (CD3+,CD8+,CD57+) | |
| 6. | How severe is the disease? | |
| Severe AA (Camitta*) | Criteria: | |
| • BM cellularity < 25% or 25–50% with < 30% residual hematopoietic cells with: | ||
| • 2 out of 3 of the following: neutrophils < 0.5 × 109/L, platelets < 20 × 109/L, | ||
| reticulocytes < 20 × 109/L | ||
| Very severe AA (Bacigalupo*) | Same as for severe AA, except neutrophil count < 0.2 instead of < 0.5 × 109/L | |
| * criteria for severe and very severe AA.1 | ||
| Abbreviations: FBC; MDS/AML, myelodysplastic syndrome/acute myeloid leukemia; T-LGL, T-cell large granular lymphocytic leukemia; DEB, diepoxybutane; MMC, mitomycin C; EBV, Epstein-Barr virus | ||
| 1. | Traditional definition | Confirmation of diagnosis |
| Pancytopenia* with hypocellular bone marrow (BM), hematopoietic tissue replaced by fat cells, in absence of abnormal infiltrate or increase in reticulin. | Full blood count, reticulocyte count, blood film examination, BM aspirate and trephine | |
| *At least 2 of the following required: Hb < 10 g/dL; platelet count < 100 × 109/L; and neutrophil count < 1.5 × 109/L. | ||
| 2. | Is the diagnosis really AA? | |
| Or is there another cause for pancytopenia and hypocellular BM? | Exclude hypocellular MDS/AML, T-LGL, myelofibrosis, lymphoma, atypical mycobacterial infection, anorexia nervosa | |
| 3. | Is the disease an inherited bone marrow failure syndrome? | Clues in medical history and clinical examination and diagnostic tests: |
| Fanconi anemia | Presence of café au lait spots, short stature, anomalies of upper extremities etc. Increased chromosome breakages of peripheral blood lymphocytes with DEB/MMC | |
| Dyskeratosis congenita | Nail dystrophy, leukoplakia and skin pigmentation, but also pulmonary fibrosis, osteoporosis, liver function abnormality. DKC-1 (X-linked), TERC (autosomal dominant), TERT gene mutation analysis | |
| Shwachmann-Diamond syndrome | History of pancreatic insufficiency, neutropenia prior to AA, short stature. SBDS gene mutation analysis | |
| 4. | What is the etiology? | |
| Idiopathic | 70–80% of cases | |
| Post-hepatitic | Liver function tests, viral studies (hepatitis A, B, C, G, but usually negative, EBV rarely) | |
| Drugs and chemicals | Careful drug and exposure history, but no tests available to prove association | |
| Environmental/occupational exposures | ||
| Paroxysmal nocturnal hemoglobinuria | ||
| Rarely: pregnancy, SLE, thymoma, eosinophilic fasciitis | Flow cytometry of GPI-anchored proteins on red cells, neutrophils and monocytes | |
| 5. | Are abnormal clones present? | |
| Paroxysmal nocturnal hemoglobinuria | Flow cytometry as above | |
| Cytogenetic clone | BM cytogenetics +/− FISH | |
| T-LGL clone | TCR gene analysis and immunophenotyping (CD3+,CD8+,CD57+) | |
| 6. | How severe is the disease? | |
| Severe AA (Camitta*) | Criteria: | |
| • BM cellularity < 25% or 25–50% with < 30% residual hematopoietic cells with: | ||
| • 2 out of 3 of the following: neutrophils < 0.5 × 109/L, platelets < 20 × 109/L, | ||
| reticulocytes < 20 × 109/L | ||
| Very severe AA (Bacigalupo*) | Same as for severe AA, except neutrophil count < 0.2 instead of < 0.5 × 109/L | |