Bone Marrow Failure

What is bone marrow failure?

Bone marrow is the soft, spongy tissue inside the larger bones of the body. It works like a factory that produces blood cells: red blood cells that carry oxygen, white blood cells that fight infection, and platelets that help the blood clot. Bone marrow failure is the term doctors use when this factory can no longer make enough healthy blood cells to meet the body’s needs.

Bone marrow failure is not a single disease. It is a group of conditions that share the same basic problem: the marrow produces too few blood cells, or the cells it makes are abnormal and do not work properly. The best-known example is aplastic anemia, a condition in which the marrow becomes largely empty of the stem cells that normally develop into blood cells. Other examples include myelodysplastic syndromes (a group of disorders in which the marrow makes faulty, immature cells) and inherited conditions such as Fanconi anemia and dyskeratosis congenita.

Bone marrow failure can affect people of any age. Inherited forms are usually recognized in childhood or early adulthood, while acquired forms, which develop during life rather than being present at birth, can appear at any age and are more often seen in young adults and in older adults. It is an uncommon condition, but a serious one, because low blood counts leave a person open to severe anemia, dangerous infections, and bleeding. With careful diagnosis and modern treatment, many people can be managed effectively, and some can be cured.

Bone marrow failure symptoms

Bone marrow failure symptoms are caused by shortages of one or more types of blood cell. Which symptoms appear, and how quickly, depends on which cell lines are affected and how far the counts have fallen. Some people develop symptoms over weeks; others notice a slow change over many months.

• Tiredness and weakness that does not improve with rest, caused by too few red blood cells (anemia)
• Shortness of breath, especially with activity, and a fast or pounding heartbeat
• Pale skin, sometimes noticed by others before the person notices it
• Frequent or long-lasting infections, such as chest infections, mouth sores, or fevers, caused by too few white blood cells
• Easy bruising, often without a clear injury, caused by too few platelets
• Bleeding from the gums or nose, heavy menstrual periods, or blood in the urine or stool
• Petechiae, which are tiny flat red or purple dots on the skin caused by small bleeds under the surface
• Dizziness or headaches, particularly when standing up

In the early stages, symptoms may be vague. A person might simply feel more tired than usual or catch colds more often. As blood counts drop further, symptoms tend to become more obvious and more serious. Fever in someone with a very low white blood cell count can be a medical emergency, because the body has little defense against bacteria.

Symptoms can also differ by type. In aplastic anemia, all three cell lines are usually low at the same time, so a person may have tiredness, infections, and bleeding together. In some myelodysplastic syndromes, only one cell line may be affected at first, often the red cells, so anemia may be the only early sign. Children with inherited bone marrow failure syndromes may also have physical features unrelated to blood counts, such as short stature, unusual thumbs or forearms, changes in skin color, or nail abnormalities, which can prompt a doctor to look for a marrow problem.

Causes and risk factors

Bone marrow failure causes fall into two broad groups: inherited and acquired. In many acquired cases, no clear trigger is ever found, and doctors describe the condition as idiopathic, meaning of unknown cause.

Inherited causes. Some people are born with gene changes that affect how blood stem cells grow, repair themselves, or survive. Well-recognized inherited bone marrow failure syndromes include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. These conditions often become apparent in childhood, although milder forms may not be diagnosed until adulthood.

Acquired causes. These develop during a person’s life. The most common mechanism in acquired aplastic anemia is thought to be an autoimmune reaction, in which the body’s own immune system mistakenly attacks the blood-forming stem cells in the marrow. Other recognized causes or contributing factors include:

• Certain medicines, including some chemotherapy drugs, some antibiotics, and some anti-seizure or anti-thyroid drugs
• Radiation exposure, including radiation therapy for cancer
• Exposure to toxic chemicals such as benzene and some pesticides
• Viral infections, including certain forms of hepatitis, Epstein-Barr virus, HIV, and others
• Some autoimmune diseases, such as lupus
• Pregnancy, in rare cases
• Paroxysmal nocturnal hemoglobinuria, a rare acquired condition in which blood cells are destroyed and which often overlaps with aplastic anemia

Myelodysplastic syndromes are more common in older adults and are often linked to age-related genetic changes in marrow cells. Previous chemotherapy or radiation therapy can also increase the chance of developing a myelodysplastic syndrome years later.

Risk factors include a family history of a bone marrow failure syndrome, prior treatment with chemotherapy or radiation, work-related exposure to industrial chemicals, and older age for the myelodysplastic group. Having a risk factor does not mean a person will develop the condition, and many people with bone marrow failure have no identifiable risk factor at all.

Bone marrow failure diagnosis

Bone marrow failure diagnosis usually begins when a routine or symptom-driven blood test shows unexpectedly low counts. Confirming the diagnosis, and identifying the specific type, requires a series of steps.

• Complete blood count (CBC). This measures the numbers of red cells, white cells, and platelets. In bone marrow failure, one or more of these is low. The doctor also looks at the reticulocyte count, which shows how many new red cells the marrow is releasing; a low number suggests the marrow is not keeping up.
• Peripheral blood smear. A drop of blood is examined under a microscope to look at the size, shape, and appearance of the cells, which can point toward one type of disorder over another.
• Bone marrow aspiration and biopsy. This is the key test. Using local anesthetic, a doctor removes a small amount of liquid marrow (aspiration) and a small core of bone with marrow inside (biopsy), usually from the back of the hip bone. A specialist then examines how many cells are present, whether they look normal, and whether there are signs of scarring or abnormal cells. In aplastic anemia the marrow is typically very sparse and replaced by fat; in myelodysplastic syndromes the marrow may be full but the cells are abnormal.
• Cytogenetic and genetic testing. Marrow or blood samples are tested for chromosome changes and specific gene mutations. These results help separate inherited from acquired forms, identify myelodysplastic syndromes, and guide treatment choices.
• Flow cytometry. This laboratory technique identifies cell types by markers on their surface and is used, among other things, to detect paroxysmal nocturnal hemoglobinuria cells.
• Additional blood tests. Doctors often check vitamin B12 and folate levels, liver and kidney function, tests for viral infections, and autoimmune markers to rule out other causes of low counts.

Imaging is not usually needed to confirm bone marrow failure itself, but a chest X-ray or other scans may be used to check for infection, and an ultrasound may be used to assess the spleen or liver. In children and young adults, doctors may also carry out a physical examination looking for the features of inherited syndromes and may recommend genetic counseling.

Aplastic anemia is often graded as non-severe, severe, or very severe based on how low the counts are and how empty the marrow appears. This grading matters because it strongly influences which bone marrow failure treatment options are recommended. At Acibadem, this condition is generally managed by the hematology department, working with laboratory and transplant specialists as needed.

Bone marrow failure treatment options

Bone marrow failure treatment options depend on the type, its severity, the person’s age and general health, and whether a suitable stem cell donor is available. Treatment usually has two goals: to keep the person safe from the immediate dangers of low blood counts, and where possible to restore the marrow’s ability to make blood.

Observation and monitoring. In mild cases with stable counts and few symptoms, a doctor may recommend regular blood tests and check-ups without active treatment at first. This is sometimes called watchful waiting. It allows treatment to begin promptly if the condition changes.

Supportive care. Almost everyone with significant bone marrow failure needs supportive care at some point. This may include transfusions of red blood cells to treat anemia, transfusions of platelets to prevent or stop bleeding, and antibiotics or antifungal medicines to treat or prevent infections. People who receive many red cell transfusions can build up excess iron in the body, so doctors may prescribe iron chelation therapy, medicines that help remove extra iron.

Immunosuppressive therapy. Because acquired aplastic anemia is often driven by the immune system attacking the marrow, medicines that calm the immune response are a standard treatment. Common combinations include antithymocyte globulin (an antibody preparation given through a vein) together with cyclosporine (a tablet or liquid taken for months). A medicine called eltrombopag, which stimulates the marrow to produce more cells, is often added. Immunosuppressive therapy works well for many people, although response can take weeks to months, relapses can occur, and some people do not respond.

Growth factors and other medicines. Depending on the diagnosis, doctors may use drugs that encourage the marrow to make particular cells, such as agents that raise white cell or platelet counts. For some myelodysplastic syndromes, medicines that alter how genes are switched on and off in marrow cells may be used. Androgens (male-type hormones) have a role in some inherited syndromes.

Hematopoietic stem cell transplantation. Also known as a bone marrow transplant, this is the only treatment that can potentially cure many forms of bone marrow failure. Healthy blood-forming stem cells from a donor, most often a matched sibling or a matched unrelated donor, are given to the patient after chemotherapy and sometimes radiation are used to clear the faulty marrow and suppress the immune system. Transplantation is generally considered first for younger people with severe disease who have a well-matched donor, and for people who do not respond to immunosuppressive therapy. It is a demanding treatment with real risks, including infection and graft-versus-host disease, in which the donor cells react against the recipient’s body, so the decision is made carefully with a specialist team. Transplant services at Acibadem are described on the Organ Transplantation page.

Surgery. Surgery is not a treatment for bone marrow failure itself. Occasionally a central venous catheter (a long-term line placed into a large vein) is inserted to make transfusions and medicines easier to give.

Rehabilitation and recovery. After intensive treatment, particularly transplantation, recovery can take many months. Physical therapy, nutritional support, and psychological support may be recommended to help rebuild strength and cope with a long illness.

Living with bone marrow failure and outlook

The outlook for bone marrow failure varies widely. Some people with mild disease live for many years with monitoring alone. Many people with severe acquired aplastic anemia respond to immunosuppressive therapy or transplantation and go on to lead active lives, although the condition can return and long-term follow-up is needed. Inherited syndromes and some myelodysplastic syndromes carry a higher long-term risk of developing leukemia, so lifelong surveillance is usually advised. Your doctor can give you a more individual picture based on your specific diagnosis, blood counts, and response to treatment.

Day to day, living with bone marrow failure often means taking sensible precautions. People with low white cell counts are usually advised to practice careful hand hygiene, avoid crowds during infection seasons, handle food safely, and report any fever promptly. People with low platelets may be asked to avoid contact sports, use a soft toothbrush, and avoid medicines such as aspirin or ibuprofen that increase bleeding unless a doctor approves them. Regular blood tests, keeping a record of transfusions, and attending all scheduled appointments are an important part of care.

The emotional impact of a rare, long-term blood disorder should not be underestimated. Fatigue, uncertainty, and repeated hospital visits can be hard on patients and families. Support groups, counseling, and open conversations with the care team can help. Some people find it useful to designate one family member to help keep track of medicines and appointments.

Frequently asked questions

What is bone marrow failure in simple terms?

Bone marrow failure means the tissue inside the bones that makes blood cells is no longer producing enough healthy red cells, white cells, or platelets. This leads to anemia, a higher risk of infection, and a tendency to bleed or bruise. It can be inherited or acquired, and it ranges from mild to life-threatening.

What are the first bone marrow failure symptoms people usually notice?

Early bone marrow failure symptoms are often vague. Many people first notice unusual tiredness, breathlessness on exertion, or pale skin. Others are alerted by easy bruising, small red dots on the skin, nosebleeds, or bleeding gums, or by infections that keep coming back. Because these signs overlap with many other conditions, only blood tests can show whether the marrow is the cause.

What are the most common bone marrow failure causes?

In adults, the most common acquired form, aplastic anemia, is usually caused by the immune system attacking the marrow, and in many cases no trigger is found. Other bone marrow failure causes include certain medicines, radiation, chemical exposure such as benzene, viral infections, and inherited gene changes. Myelodysplastic syndromes are more often related to age or to previous cancer treatment.

How is bone marrow failure diagnosis confirmed?

Bone marrow failure diagnosis starts with a complete blood count showing low cell numbers. The condition is confirmed with a bone marrow aspiration and biopsy, in which a small sample of marrow is taken from the hip bone and examined under a microscope. Genetic tests, flow cytometry, and additional blood tests help identify the exact type and rule out other causes.

What are the main bone marrow failure treatment options?

Bone marrow failure treatment options include supportive care with transfusions and infection prevention, immunosuppressive medicines that stop the immune system attacking the marrow, drugs that stimulate blood cell production, and stem cell transplantation from a donor. The choice depends on the type, severity, age, general health, and donor availability, and is made together with a hematologist.

Can bone marrow failure be cured?

Some forms can be cured. Stem cell transplantation can replace the failing marrow with healthy donor cells and is potentially curative for many people, particularly those who are younger and have a well-matched donor. Immunosuppressive therapy can produce long-lasting remissions in acquired aplastic anemia, although relapse is possible. Other forms are managed as long-term conditions rather than cured.

Is bone marrow failure the same as leukemia?

No. In bone marrow failure the marrow produces too few cells; in leukemia the marrow produces too many abnormal white cells that crowd out healthy ones. However, the two are related: some bone marrow failure conditions, especially inherited syndromes and myelodysplastic syndromes, carry an increased risk of developing leukemia over time, which is one reason for regular monitoring.

When to see a doctor

Anyone with persistent unexplained tiredness, pale skin, easy bruising, or infections that keep returning should arrange to see a doctor so that blood tests can be done. For people already diagnosed with bone marrow failure, certain warning signs need urgent medical attention, because low blood counts can make ordinary problems dangerous very quickly.

Seek emergency care right away if you notice:

• A fever of 38°C (100.4°F) or higher, chills, or shaking, especially if your white cell count is known to be low
• Bleeding that will not stop, including a nosebleed lasting more than a few minutes or bleeding from the gums that continues
• Blood in the urine, black or bloody stools, or vomiting blood
• A sudden severe headache, confusion, weakness on one side, or changes in vision, which could signal bleeding in the brain
• Severe shortness of breath, chest pain, or a racing heartbeat at rest
• A rapidly spreading rash of small red or purple dots or large new bruises appearing without injury
• Fainting or feeling unable to stay upright

If you are receiving treatment and develop new symptoms such as a sore throat, cough, burning when passing urine, redness around a catheter site, or mouth ulcers, contact your care team the same day, as these can be early signs of infection that need prompt treatment.