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Aplastic Anaemia

Aplastic anaemia (AA) is a severe haematologic condition characterised by the body's failure to produce sufficient blood cells. It affects all blood cell types: red blood cells, white blood cells, and platelets. This condition is linked to cancer and various cancer syndromes. Blood cells are produced in the bone marrow by stem cells; in aplastic anaemia, these stem cells are mostly absent and replaced by fat.

Signs and Symptoms

Patients with aplastic anaemia display a variety of symptoms due to the deficiency in different blood cell types. Anaemia can cause fatigue, pale skin, severe bruising, and a fast heart rate. Low platelet counts increase the risk of bleeding, bruising, and petechiae, while low white blood cell counts heighten the risk of infections.

Causes

Aplastic anaemia can result from immune diseases, exposure to certain chemicals, drugs, radiation, or infections. However, in about half of the cases, the cause remains unknown. Known risk factors include smoking, family history, ionising radiation, and prior chemotherapy. Specific drugs, such as chloramphenicol and carbamazepine, have been linked to the condition, though the probability is low. Exposure to ionising radiation, as in the case of Marie Curie, is also a known cause. Autoimmune disorders where white blood cells attack the bone marrow can lead to aplastic anaemia, as can infections like hepatitis and HIV.

Diagnosis

Diagnosis of aplastic anaemia is confirmed through a bone marrow biopsy, which reveals a deficiency in blood stem cells. Patients often undergo various blood tests to identify other potential causes, including a complete blood count, renal function tests, liver enzymes, thyroid function tests, and vitamin B12 and folic acid levels. Additional diagnostic tests may include viral studies, chest X-rays, and imaging tests to rule out other conditions.

Pathogenesis

The central hypothesis is that aplastic anaemia results from T-cell-mediated autoimmunity, leading to the destruction of bone marrow. This involves the overproduction of pro-inflammatory cytokines and apoptosis of haematopoietic stem cells. Increased levels of Th17 cells and interferon-γ-producing cells are observed in patients. The role of the bone marrow microenvironment is very important, with components like stromal cells and local cytokine gradients supporting stem cell production.

Treatment

Treatment aims at immune suppression, achieved through daily medication or bone marrow transplants in severe cases. For younger patients with a matched sibling donor, bone marrow transplant is often the first-line treatment. For others, immunosuppressive therapy with antithymocyte globulin (ATG) and ciclosporin is preferred. Chemotherapy with agents like cyclophosphamide is also an option but is more toxic. Follow-up includes regular blood counts and monitoring for conditions like paroxysmal nocturnal haemoglobinuria (PNH).

Prognosis

Untreated severe aplastic anaemia has a high mortality rate. Modern treatments have improved the five-year survival rate to over 85%, especially in younger patients. For those undergoing bone marrow transplants, survival rates are higher if the donor is a matched sibling. However, relapses are common, and there is a risk of progression to conditions like myelodysplastic syndrome and leukaemia.

Epidemiology

Aplastic anaemia is a rare disorder with an incidence of 0.7–4.1 cases per million people worldwide. It most commonly affects individuals aged 15–25 and those over 60. The disease is usually acquired rather than inherited, often linked to environmental exposures. Idiopathic aplastic anaemia accounts for 75% of cases, where the underlying cause is unknown.

Notable Cases

  • Marie Curie
  • Eleanor Roosevelt
  • Donny Schmit
  • Ted DeVita
  • Demetrio Stratos
  • John Dill
  • Robert McFall

Aplastic anaemia is a complex condition requiring comprehensive diagnostic and therapeutic approaches, with significant implications for patient prognosis and management.


Self-assessment MCQs (single best answer)

What characterises aplastic anaemia?



Which type of cells are deficient in aplastic anaemia?



What is a common symptom of low platelet counts in aplastic anaemia?



Which of the following is a known risk factor for aplastic anaemia?



What is the primary method to confirm a diagnosis of aplastic anaemia?



What is the central hypothesis for the pathogenesis of aplastic anaemia?



Which treatment is often the first-line for younger patients with a matched sibling donor?



What is the five-year survival rate for patients receiving modern treatments for severe aplastic anaemia?



What percentage of aplastic anaemia cases are idiopathic?



Which notable individual suffered from aplastic anaemia due to exposure to ionising radiation?



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