Aplastic Anemia

What happens in aplastic anemia

All blood cells come from hematopoietic stem cells in the bone marrow. In aplastic anemia, most of these stem cells are lost, and the marrow becomes "empty", replaced by fat. With too few stem cells:

• low red cells (anemia) cause tiredness and breathlessness
• low white cells (neutropenia) cause infections
• low platelets (thrombocytopenia) cause bruising and bleeding

Unlike leukemia, the marrow is not filled with abnormal cells; it is simply empty.

Causes

Immune-mediated (most cases)

In most people, no trigger is found ("idiopathic"). T-cells of the immune system attack the marrow stem cells. This is why immune-suppressing treatment works.

Known triggers

• Medicines: some antibiotics (chloramphenicol), anti-seizure medicines, gold, some anti-thyroid drugs and NSAIDs, rarely
• Chemotherapy and radiation, which cause expected, usually temporary marrow suppression
• Toxins: benzene and some pesticides
• Viral infections: seronegative hepatitis (aplastic anemia following hepatitis of unknown cause), Epstein-Barr virus, HIV
• Pregnancy, rarely
• Autoimmune diseases such as lupus

Inherited bone marrow failure

About 1 in 4 children and some young adults with marrow failure have an inherited cause, such as Fanconi anemia, dyskeratosis congenita or other telomere disorders. Identifying these changes treatment and family testing.

Related conditions

Aplastic anemia overlaps with paroxysmal nocturnal hemoglobinuria (PNH), a condition causing red cell destruction and clots, and can later evolve into myelodysplastic syndrome or leukemia in a minority of patients.

Symptoms

Symptoms develop over weeks to months, or sometimes quickly:

• tiredness, weakness and paleness
• shortness of breath on exertion and a fast heartbeat
• frequent or severe infections, mouth ulcers and fevers
• easy bruising, pinpoint red spots (petechiae), nosebleeds, bleeding gums, heavy periods
• headaches and dizziness

Diagnosis

1. Complete blood count: low red cells, white cells and platelets, with a low reticulocyte count (few new red cells being made).
2. Blood film to exclude abnormal cells.
3. Bone marrow biopsy: the key test. It shows a marrow with very few blood-forming cells (usually under 25 percent of normal cellularity) and no cancer or fibrosis.
4. Additional tests: PNH testing by flow cytometry, vitamin B12 and folate, liver tests and viral tests, and chromosome and genetic tests for inherited syndromes and MDS.

Severity

Treatment

Supportive care

• Red cell and platelet transfusions as needed, using irradiated and leukocyte-reduced products.
• Prevention and fast treatment of infections: antibiotics, antifungals and urgent assessment for any fever.
• Iron chelation if repeated transfusions cause iron overload.
• Avoiding medicines that affect platelets, such as aspirin and NSAIDs, unless advised.

Stem cell (bone marrow) transplant

A transplant replaces the failed marrow with healthy donor stem cells and can cure the condition. It is the first-choice treatment for younger patients with severe aplastic anemia who have a matched sibling donor, and is increasingly used with matched unrelated or partially matched donors.

Immunosuppressive therapy

For people who are not transplant candidates, standard treatment combines:

• horse anti-thymocyte globulin (ATG), an infusion that suppresses the T-cells attacking the marrow
• cyclosporine, taken by mouth for months
• eltrombopag, a medicine that stimulates remaining stem cells

Most patients respond, usually over 3 to 6 months. Some relapse and need further treatment, and a small proportion later develop MDS, leukemia or PNH, so long-term monitoring is needed.

Mild disease

Non-severe aplastic anemia may only need monitoring, or treatment with cyclosporine and eltrombopag if counts fall or transfusions are needed.

Outlook

Before modern treatment, severe aplastic anemia was usually fatal. Today, long-term survival after either transplant or immunosuppressive therapy is high, generally around 70 to 90 percent depending on age, severity and treatment, and better in children and young adults. Quality of life after successful treatment is usually good.

Living with aplastic anemia

• Take your temperature whenever you feel unwell, and call your care team immediately for fever.
• Wash hands often, avoid crowds and sick contacts when counts are low, and follow food safety advice.
• Use a soft toothbrush and electric razor; avoid contact sports while platelets are low.
• Check with your team before vaccines; live vaccines may be unsafe.
• Women considering pregnancy need specialist advice, as pregnancy can trigger relapse.

Frequently asked questions

What causes aplastic anemia?

Most cases are caused by the immune system attacking the bone marrow's stem cells, usually without a known trigger. Some follow certain medicines, toxins such as benzene, viral hepatitis or pregnancy. A minority, especially in children, are due to inherited conditions such as Fanconi anemia.

What are the first signs of aplastic anemia?

Early signs include tiredness, paleness, breathlessness on exertion, frequent infections, easy bruising, tiny red spots on the skin, nosebleeds and bleeding gums. A blood test showing low levels of all three blood cell types prompts further investigation.

Can aplastic anemia be cured?

Yes, in many cases. A stem cell transplant can cure it, particularly in younger people with a matched donor. Immunosuppressive therapy restores blood counts in most others, although some relapse and need further treatment. Long-term follow-up is important.

What is the life expectancy with aplastic anemia?

With modern treatment, most people survive long term, with survival rates of roughly 70 to 90 percent depending on age, severity and treatment type. Untreated severe aplastic anemia is life-threatening, so prompt referral to a hematologist matters.

Is aplastic anemia a type of cancer?

No. Aplastic anemia is bone marrow failure, not cancer. The marrow is empty rather than filled with abnormal cells. However, a minority of patients later develop myelodysplastic syndrome or leukemia, which is why regular monitoring continues after treatment.