Aplastic anemia. Agranulocytosis
Aplastic anemia is a rare stem cell disorder leading to pancytopenia and hypoplastic bone marrow, characterised by the bone marrow's inability to produce peripheral blood cells and their progenitors. It is helpful to remember that the term ‘aplastic’ = failure of an organ or tissue to develop or function normally. Therefore, it is fair to say, aplastic anemia is the failure of the bone marrow to function, in this case, at all.
Peripheral pancytopenia is usually present, aplastic anaemia however can only be diagnosed on observation of bone marrow where there is absence of non lymphoid hematopoietic cells. If the hematopoietic marrow has been suppressed or replaced by infiltration of other cells, a diagnosis of aplastic anemia cannot be made. Therefore we can say, for aplastic anemia to be diagnosed, we need ‘empty’ bone marrow. At least two of RBC, platelet and neutrophil count should be low as well.
There are a range of different causes of aplastic anemia, all of which lead to this empty bone marrow state. The most common causes are:
- Marrow aplasia (15%)
- Autoimmune aplastic anemia
- Idiopathic (most common single cause)
- Drug induced
- Infections (hepatitis, Epstein-Barr)
- Fanconi anaemia (most common congenital - AR or XL)
- Autoimmune-mediated failure of single hematopoietic lineages
- Agranulocytosis
- Pure RBC aplasia
- Direct stem cell toxicity
- Other aplastic states such as pregnancy or inherited bone marrow failure
Aplastic anaemia generally presents with neutropenia, anemia, and/or thrombocytopenia.
In autoimmune aplastic anemia we see CD4 T cell mediated AI attack directed against the haematopoietic system, creating a proinflammatory environment in the bone marrow that results in apoptosis of hematopoietic stem cells. In congenital aplastic anemia we see a different path, it varies based on the precise cause, but taking the most common, fanconi anaemia, there is an underlying defect in the DNA damage repair mechanisms which causes the failure of the marrow.
Diagnostic criteria:
- At least two of the following along with bone marrow hypocellular
- Hemoglobin <100g/L
- Platelet count <50 x 10*9/L
- Absolute neutrophil count <1.5 x 10*9/L
Main treatment modalities are:
- Withdrawal of potential etiological agent (e.g. drugs)
- Immunosuppressive therapy
- Allogeneic stem cell transplantation
- Eltrombopag (oral thrombopoietin receptor agonist)
- Supportive care with blood transfusions