Makindo Medical Notes

Related Subjects: | Alpha Thalassaemia | Anaemia of Chronic Disease | Aplastic Anaemia

Aplastic anaemia is a rare but serious condition characterized by pancytopenia and hypocellular bone marrow. In approximately 75% of acquired cases, the cause is unknown (idiopathic). Autoimmune mechanisms are believed to play a significant role, and patients may respond to immunosuppressive therapy.

About Aplastic Anaemia

• Causes pancytopenia due to bone marrow failure (aplasia or hypoplasia).
• Bimodal age distribution: peaks at ages 15–25 and in the elderly.
• Potentially fatal due to severe anaemia, leukopenia, and thrombocytopenia.

Aetiology

• Aplastic anaemia is the primary syndrome of bone marrow failure.
• Often idiopathic; immune-mediated destruction of haematopoietic stem cells by cytotoxic T cells is implicated.
• Results in pancytopenia and a hypocellular bone marrow.

Clinical Features

• Anaemia (Low Hb): Tiredness, pallor, fatigue.
• Leukopenia (Reduced WCC): Recurrent infections, fever, cough, chest and urinary tract infections.
• Thrombocytopenia (Reduced Platelets): Bleeding gums, mucous membranes, petechiae, bruising, increased risk of spontaneous bleeding.
• Typically no lymphadenopathy or organomegaly; lymph nodes, liver, and spleen are usually normal.

Causes

• Idiopathic (Approximately 50%): Immune-mediated destruction of bone marrow stem cells.
• Drugs and Toxins:
  • Chemotherapy agents (alkylating agents, antimetabolites).
  • Benzene and other solvents.
  • Certain medications: Chloramphenicol, carbimazole, some anticonvulsants (e.g., phenytoin), sulfonamides, gold compounds, and rarely NSAIDs.
• Radiation Exposure: High doses of ionizing radiation.
• Viral Infections: Hepatitis viruses (non-A, non-B, non-C), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HIV, Parvovirus B19.
• Autoimmune Diseases: Systemic lupus erythematosus (SLE), graft-versus-host disease.
• Pregnancy: Rare cases associated with pregnancy.
• Inherited Conditions: Fanconi anaemia, dyskeratosis congenita.
• Paroxysmal Nocturnal Haemoglobinuria (PNH): A clonal stem cell disorder that can lead to aplastic anaemia.
• Other Haematological Diseases: Myelodysplastic syndrome, leukaemia, lymphoma.

Investigations

• Full Blood Count (FBC): Shows pancytopenia—low haemoglobin, low white cell count (especially neutropenia), and low platelet count.
• Blood Film: Reduced numbers of all cell lines; cell morphology is typically normal.
• Bone Marrow Biopsy (Aspirate and Trephine): Hypocellular or acellular marrow with fatty infiltration confirms the diagnosis.
• Reticulocyte Count: Low, indicating decreased red cell production.
• Cytogenetic Analysis: To exclude other haematological disorders like leukaemia or myelodysplasia.
• Viral Serology: Testing for hepatitis viruses, EBV, HIV, Parvovirus B19.

Severity and Prognosis

• Severe Aplastic Anaemia:
  • Neutrophils < 0.5 x 10⁹/L.
  • Platelets < 20 x 10⁹/L.
  • Reticulocytes < 20 x 10⁹/L.
  • Bone marrow cellularity < 25% of normal.
• Very Severe Aplastic Anaemia:
  • Neutrophils < 0.2 x 10⁹/L.
• Without appropriate treatment, mortality exceeds 50% if severe cytopenias persist beyond three weeks.

Management

• Supportive Care:
  • Transfusions of red blood cells and platelet concentrates (preferably leukocyte-depleted to reduce alloimmunization).
  • Prompt treatment of infections with broad-spectrum antibiotics.
  • Implement protective measures to reduce infection risk (e.g., isolation, hygiene protocols).
• Immunosuppressive Therapy:
  • First-line treatment for patients without a suitable donor or older patients.
  • Combination of antithymocyte globulin (ATG) and cyclosporine A.
  • Corticosteroids may be added to reduce serum sickness from ATG.
  • Response rates of up to 70%, but there is a risk of relapse and clonal evolution.
• Haematopoietic Stem Cell Transplantation (HSCT):
  • Allogeneic transplant from an HLA-matched sibling or matched unrelated donor.
  • Curative potential, especially in younger patients (< 40 years old).
  • Success rates up to 80% with matched sibling donors.
• Elimination of Causative Agents:
  • Avoid exposure to suspected drugs or toxins.
  • Treat underlying infections or associated conditions.
• Growth Factors:
  • Use of granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) is generally not beneficial in aplastic anaemia.

References

• NHS UK: Aplastic Anaemia
• UpToDate: Aplastic Anaemia
• Aplastic Anemia and MDS International Foundation