25. The aplastic anemia

Page created on April 8, 2022. Last updated on December 18, 2024 at 16:58

Written by ms. Worldwide, edited by Nikolas.

Introduction and epidemiology

Aplastic anaemia (AA) refers to pancytopenia caused by bone marrow hypoplasia/aplasia. It’s a rare disorder, affecting 2 per million.

It’s distinct from bone marrow failure, in which pancytopaenia can be caused by bone marrow replacement (by tumour, fibrosis, or myelodysplastic syndromes). It might be anywhere from mild to severe.

Etiology

Mostly idiopathic (50%), but can also be due to known factors such as:

1. Direct injury
   1. Benzene
   2. NSAIDs
   3. Antiepileptics
   4. Antibiotics (sulphonamides and chloramphenicol)
   5. Infections (sepsis, hepatitis, parvovirus B19)
2. Immune destruction
   1. Idiopathic
   2. Eosinophilic fasciitis
   3. Thymoma
3. Constitutional genetic defects
   1. Telomere disease
   2. Fanconi anaemia

Predictable bone marrow hypoplasia, for example due to anticancer treatment, is not considered aplastic anaemia.

Pathomechanism

Idiopathic aplastic anaemia might be due to aberrant immune response and is increased in pregnancy and rheumatologic disorders, which leads to immune destruction of haematopoietic cells.

Classification

Based on Camitta criteria, which classifies the severity according to the bone marrow cellularity, absolute neutrophil count, platelet count, and reticulocyte count:

• Severe
  • Bone marrow cellularity <25%
  • And two or more of the following:
    • Neutrophile count <0,5 G/L
    • Platelet count <20 G/L
    • Reticulocyte count <20 G/L
• Very severe
  • Neutrophils below <0,2 G/L
• Non-severe
  • Hypocellular bone marrow but not meeting criteria for severe AA

Clinical features

The presentation of aplastic anaemia is usually insidious, with an inciting event (medication change, infection) some weeks before. The clinical features are those of anaemia, neutropaenia, and thrombocytopaenia. Presence of hepatosplenomegaly or lymphadenopathy points to another diagnosis.

Diagnosis and evaluation

Complete blood count show pancytopenia, and normocytic or macrocytic anaemia. The reticulocyte count is low and EPO level is high. On blood smear, the cells have normal morphology.

Bone marrow biopsy is obligatory and will show a fat-filled (“dry”) marrow containing very few cells. The few RBC’s will have normal morphology. HLA typing is obligatory in those <60 as it influences choice of therapy. Young patients should be evaluated for congenital causes.

Treatment

It is important to isolate the patients, so they won’t catch infections, give broad-spectrum AB in case of fever, and give necessary transfusions of RBCs and platelets if needed.

If an underlying cause is found, withdrawal of the triggering factor restores the bone marrow. However, the bone marrow will need some time to recover.

For young patients (<40-50 years), hematopoietic cell transplantation is indicated as first line therapy. In older patients or while waiting for transplant, immunosuppressive therapy, namely anti-thymocyte globulin + cyclosporin + glucocorticoids, is used. Granulocyte-monocyte colony stimulating factors (GM-CSF) may improve the pancytopaenia.