The central portion of bones is filled with a spongy red tissue called bone marrow. The bone marrow is essentially a factory producing the cells of the blood: red cells that carry oxygen from the lungs to all areas of the body, white cells that fight infection by attacking and destroying germs, and platelets that control bleeding by forming blood clots in areas of injury.

Continuous production of blood cells is necessary all through life because each cell has a finite life span once it leaves the bone marrow and enters the blood: red cells--120 days, platelets--6 days, and white cells--one day or less!

The bone marrow contains a small number of precious stem cells. Just as plant seeds give rise to both mature plants and new seeds for the next generation of plants, so do the bone marrow stem cells produce blood cells and new stem cells in a lifelong cycle of production and self-renewal. Bone marrow stem cells require a proper environment for normal function. Just as a seed cannot grow in poor soil, bone marrow stem cells cannot survive and multiply in a poor environment.

Confirmation of the diagnosis requires examination of a small sample of bone marrow under the microscope. Aspiration and biopsy of the bone marrow is easily carried out in the examining room or hospital bed by inserting a sturdy needle into the large pelvic bone just beneath the belt line on either side of the spine. This procedure is made more tolerable by the use of Novocain-like drugs to "numb up" the skin and bone.

In aplastic anemia, the bone marrow biopsy shows a great reduction in the number of cells in the bone marrow, with a normal appearance of the few remaining cells. The diagnosis of aplastic anemia is usually made or confirmed by a hematologist- a specialist in blood disorders.

Blood transfusion: Aplastic anemia patients are often given transfusions. Anemia is corrected by red cell transfusions. Since anemia in itself is not an emergency, red cell transfusions are usually given only when symptoms are not relieved by restriction of activity. By contrast, bleeding due to low platelets is an acute medical emergency which should be treated with platelet transfusions to prevent fatal hemorrhage. You may be asked to provide platelet donors. Do not ask close family members to donate platelets until after a bone marrow transplant has been done or ruled out since this may interfere with the effectiveness of a bone marrow transplant if a family member donor is found.

Platelets are collected from donors through a process called hemapheresis. Donating usually takes three hours. Platelets are collected from a vein in the donor's arm, passed through a blood-separating machine and returned to the donor. The platelets that are removed are then given to the aplastic anemia patient. The donor's body replaces the platelets within a day or two.

Antibiotics: Because of their extremely short life span, white cells cannot be effectively replaced by a transfusion. Therefore, control of infection depends on prompt, appropriate intravenous antibiotic therapy as soon as fever or other signs of infection appear.

Isolation: To prevent transfer of infection to aplastic anemia patients, they must often be isolated from even healthy people ("reverse quarantine"). Necessary visitors may have to wear masks and gown and must always thoroughly wash hands before touching the patient.

1. Take charge of your illness!
2. Research all you can about aplastic anemia and treatment options.
3. Gather information from as many people as possible: health professionals and other patients.
4. Don't be afraid to ask questions from different sources until you fully understand the answers.
5. Record information in a notebook. Take a tape recorder to appointments and meetings.
6. Encourage friends and family to become platelet and bone marrow donors.
7. Join a support group and read about ways to cope.
8. Check with the doctor about what things to avoid.

For young patients in relatively good health prior to transplant, and who have a matched donor, more than half are successfully cured by bone marrow transplantation. For patients who do not have a matched donor, who are over 40 years of age or who are not good candidates for bone marrow transplantation, other forms of therapy are being used.

Immunosuppressive therapies work with a patient's immune system. One theory about aplastic anemias that the patient's immune system is fighting against itself, thereby interfering with production of blood cells. These drugs are believed to work by stimulating the bone marrow to produce cells or by reducing the patient's immune response and thereby allowing the bone marrow to work. ATG, antithymocyte globulin, or ALG, antilymphocyte globulin, are two types of immunosuppressive therapies that have been used for treating aplastic anemia.

Another immunosuppressive drug is cyclosporin, which may be given alone or in combination with androgens, antilymphocyte globulin or serum. It is thought that cyclosporin plus androgens may stimulate blood cell production.

Hematopoietic growth factors are products of the new genetic engineering. These are copies of substances which occur naturally in the human body, but produced in larger quantities in the laboratory Colony stimulating factors (CSFs) act to stimulate colonies of cells, such as red cells. Interleukin-3 (IL-3) stimulates production of other cells. It is thought that a combination of the growth factors might work in treating aplastic anemia.

Other drug therapies are being developed all the time. Your doctor will be able to help you explore these options.

Don't blood transfusions replace the cells needed by aplastic anemia patients?
Unfortunately, blood transfusions are only a temporary solution to some of the problems of aplastic anemia patients. Consider each type of cell in turn:

1) Red Cells- Red cells are the easiest to replace by transfusion. There are only 4 major blood types, so "matching" is usually easy, and transfused cells may remain in the body for a month or longer. However, after years of regular red cell transfusions, patients being to accumulate toxic amounts of iron (carried inside the red cells) in critical body organs, such as the liver or heart. Iron overload from transfusions is eventually fatal.

2) Platelets- Successful long-term platelet transfusion therapy is a challenge. Since the normal life span of a platelet is so short, transfuses platelets may only survive a few days; thus regular platelet transfusions several times a week may be needed. In addition, platelets carry tissue-type "markers" that are almost unique for each person. Patients "learn" to recognize foreign platelets and produce antibodies that destroy the transfused platelets instantly. Thus, aplastic anemia patients rapidly develop a need for "matched" platelets, that is platelets from donors whose tissue-type markers resemble the patient's own markers. To support one small child with matched platelets for a year, 20 matched donors may be needed.

3) White Cells- White cells cannot be effectively supplied by transfusion. The number of white cells obtained from donors is so short (a few hours) that routine white cell transfusion is technically impossible.

What are the causes of aplastic anemia?
Aplastic anemia has been clearly linked to radiation, environmental toxins, insecticides, and drugs in much the same fashion that cancer has been linked to these agents. Benzene-based compounds, airplane glue, and drugs such as chloramphenicol have been linked to aplastic anemia. In some individuals, aplastic anemia is believed to be caused by a virus. To date the exact cause of the disease in over half the cases is unknown, or idiopathic.

Are there any experimental treatments available for those who do not respond to ATG and do not have a bone marrow transplant match?
Yes. There are several alternative therapies that can be tried and some are successful to some extent. These include the use of cytokines (growth factors) or granulocyte monocyte colony stimulating factor (GM-CSF) or erythropoietin (EPO). These are approved and commercially available cytokines that are available to all physicians. In addition, several experimental cytokines are being evaluated and could potentially be useful in some aplastic anemia patients. These include interleukin 3, monocyte colony stimulating factor, stem cell factor (SCF or C-kit ligand) and IL-6. Several newer cytokines are being developed and will be available for study in the near future.

How do I find out where in my area there is experimental research going on?
In the United States of America, nearly all experimental therapy for aplastic anemia is being carried out at hospitals associated with either one of the medical schools, or one of the NIH designated cancer center. In addition, experimental therapies are being carried out at the National Institutes of Health in Bethesda, Maryland. A letter or call to the Hematology Division (either pediatric or adult) of the nearest medical school or designated cancer center should result in information concerning the availability of experimental therapy.

What activities should I avoid?
Patients with low red cell counts should avoid excessive exercise, going to high altitudes or any activity that brings on a fast heart rate, any chest pain or severe shortness of breath. Patients will low white counts may be more susceptible to infection with bacteria not viruses. These are usually acquired from cuts in the skin or lining of the mouth or throat which might result from dental work, burns from hot food, etc. Patients with low platelets should avoid activities that result in trauma, especially head trauma. These would include contact sports such as football, skiing, hockey, etc.

• aplastic anemia: bone marrow failure; for unknown reasons, production of blood cells slows or stops.
  
• antibody: a complex molecule produced by lymph tissue in response to the presence of an antigen; antibodies neutralize the effect of the antigen.
  
• antigen: foreign substance which is not usually part of the body's makeup, and that stimulates antibody production; this antibody reacts specifically with a particular antigen to destroy or weaken it.
  
• bacteria: organism that can cause infection.
  
• bone marrow: soft tissue within the bones where blood cells are manufactured.
  
• bone marrow aspiration: test in which a sample of bone marrow cells is removed with a needle and examined under a microscope.
  
• bone marrow biopsy: procedure in which a small piece of bone marrow tissue is removed with a needle; sample is processed by softening the bone and examining thin slices of the softened bone under a microscope.
  
• bone marrow transplant: procedure in which bone marrow filled with disease is destroyed by radiation or chemotherapy and then replaced with healthy cells from a donor.
  
• chromosome: a rodlike structure that appears in the nucleus of a cell during division; contains the genes responsible for heredity.
  
• complete blood count: CBC; amount or level of blood cells: white cells, red cells and platelets.
  
• cross match: type and cross; test in which the blood cells of a donor and a recipient are mixed together to determine if they are compatible.
  
• culture: procedure used to identify the source of infection; specimen of blood, urine, sputum or stool is taken and tested to determine the type of infection and the appropriate antibiotic.
  
• differential: percent of different types of blood cells in the blood.
  
• hemoglobin: Hg; iron-containing coloring in the red cells that combine with oxygen from the lungs and carries it to the body's cells.
  
• histocompatibility antigens: HLA; a group of DNA substances in chromosomes that determine whether certain tissues can be transplanted; also can be used to determine the most compatible platelet donors.
  
• human leukocyte antigen: HLA; the tissue typing test done on white cells to determine if a donor and recipient are compatible.
  
• immunosuppression: decrease in the ability of the body's normal immune response to the invasion of foreign material.
  
• lymphocyte: a type of white cell that fights infection by producing antibodies and other defense substances; occurs in 2 forms: B cells that recognize specific antigens and produce antibodies against them, and T cells that are agents of the immune system.
  
• neutropenia: low neutrophil (poly) count.
  
• pancytopenia: low number of blood cells.
  
• petechiae: tiny red dots on the skin due to bleeding under the skin caused by low platelet counts.
  
• peripheral blood: blood in the bloodstream.
  
• platelet: blood cell that prevents bleeding and bruising.
  
• red blood cell: oxygen carrying cell in the blood which contains the pigment hemoglobin, produced in the bone marrow; erythrocyte.
  
• stem cell: cell from which platelets, red blood cells and white blood cells grow in the one marrow.
  
• white blood cells: blood cells which fight infection.