Aplastic Anemia
Aplastic anemia (AA) is a disease that occurs when the bone marrow stops producing enough stem cells to make the red blood cells, white blood cells, and platelets that the body needs. With aplastic anemia, the patient's bone marrow is usually found to be hypoplastic, meaning there are few, if any, functioning stem cells. This results in abnormally low numbers of red cells, white cells, and platelets in the bloodstream. The name "aplastic anemia" comes from the words aplasia, the condition in which cells fail to develop, and anemia, a shortage of red blood cells.
Aplastic anemia is generally thought to be the result of the patient's own immune system reacting against the bone marrow, interfering with its ability to make blood cells. Aplastic anemia can also occur when the bone marrow is damaged by chemotherapy, some medications, or exposure to certain toxic substances.
Aplastic anemia:
  • is a rare disease, with about 600 to 900 new diagnoses each year in the U.S. (2 to 3 people per million). Aplastic anemia is two to three times more common in Asian countries than in the U.S. and Europe, with about 6,000 to 7,000 new diagnoses reported annually worldwide.
  • is not contagious. You cannot "catch" aplastic anemia from exposure to someone with the disease.
  • is rarely hereditary. In almost all cases you cannot inherit it from your parents or pass it on to your children.
  • can appear at any age but is most commonly diagnosed in children aged 2-5 years, young adults aged 20-25 years, and adults aged 55-60 years.
  • is more common among Asian-Americans than other ethnic groups in the U.S.
  • can be treated in many ways but can be cured only with a bone marrow transplant or stem cell transplant.
Symptoms of Aplastic Anemia
The most common symptom of AA is feeling extremely tired or weak (fatigue), which is the result of having a low red blood cell count. A low red blood cell count also can cause shortness of breath; rapid pulse; dizziness, especially when standing up; headache; coldness in your hands or feet; pale gums, nail beds, and skin (pallor); chest pain; decreased alertness; and shortened attention span.
Red blood cells carry hemoglobin, an iron-rich protein that transports oxygen to the body. If you don't have enough hemoglobin-carrying red blood cells, your heart has to work harder to circulate the reduced amount of oxygen in your blood.
White blood cells help fight infections. Symptoms of a low white blood cell count include fevers, frequent infections that can be severe, and flu-like illnesses that linger.
The cells called platelets stick together to seal cuts and stop bleeding. Symptoms of a low platelet count include the tendency to bruise and bleed easily and to have bleeding that may be hard to stop. Common types of bleeding include nosebleeds, bleeding gums, pinpoint red bleeding spots on the skin (petechiae), and blood in the stool. Women also may have heavy menstrual bleeding.
Because many of these symptoms can result from other conditions, a patient who experiences one or more symptoms of aplastic anemia does not necessarily have aplastic anemia. For the same reason, aplastic anemia may not be recognized or diagnosed at first. It is essential to consult a doctor for a professional diagnosis.
Causes and Risk Factors
In about 50% of cases, aplastic anemia is considered to be idiopathic, meaning that the cause of the disease is unknown.
Acquired aplastic anemia refers to those cases where environmental factors and physical conditions seem to be associated with development of the disease. These include
  • treatment with high-dose radiation or chemotherapy for cancer
  • exposure to toxic chemicals, including some pesticides and insecticides
  • use of some medications, such as chloramphenicol, which is used to treat bacterial infections, and gold compounds used to treat rheumatoid arthritis
  • certain blood diseases, autoimmune disorders (e.g., lupus), and serious infections
  • pregnancy (rarely)
Hereditary aplastic anemia is relatively rare, but does occur with diseases such as Fanconi's anemia, Dyskeratosis Congenita, and Shwachman-Diamond syndrome.
Diagnosis of Aplastic Anemia
To diagnose aplastic anemia, a doctor will review the patient's medical history, current symptoms, and ask questions like these:
  • Do you live or work in an area where you are exposed to toxic chemicals or radiation?
  • What medications do you take?
  • Have you ever had hepatitis, mononucleosis or another viral infection?
  • Is there a family history of aplastic anemia or other blood disorders?
A blood sample will be taken to measure levels of red cells, white cells, and platelets. The resulting report, called a Complete Blood Count (CBC), will be compared to normal blood counts to identify any counts that may be too low. Aplastic anemia is indicated when all three cell counts are very low but the cells look normal.
To confirm the diagnosis the doctor will perform a pair of tests simultaneously: bone marrow aspiration (BMA) and bone marrow biopsy (BMB). The BMA provides information about the presence or absence of abnormal cells in the marrow. The BMB provides information about blood production in the marrow through the examination of the quantity (also knows as the cellularity) and quality of bone marrow cells.
The Mechanism of Aplastic Anemia
In the human body, stem cells in the bone marrow reproduce (clone) themselves to produce a population of stem cells. Stem cells mature into:
  • red blood cells (erythrocytes). They carry hemoglobin, an iron-rich protein that transports oxygen to the body.
  • white blood cells (leukocytes). As part of your immune system they destroy "bad" cells: invading or foreign cells like bacteria and viruses, and abnormal cells.
  • platelets (thrombocytes). They help blood clot.
In healthy people these cells enter the circulating blood as they become mature. In a person with aplastic anemia, stem cells do not mature into enough functioning cells, leading to the lack of cells in the bone marrow and bloodstream. Immature blood cells have the following names:
  • reticulocytes: red blood cell precursors
  • myelocytes: white blood cell precursors
  • megakaryocytes: platelet precursors
The low blood counts and resulting symptoms experienced by aplastic anemia patients result from the lack of mature cells:
  • anemia: insufficient red blood cells
  • neutropenia: insufficient white blood cells
  • thrombocytopenia: insufficient platelets
Types of Aplastic Anemia
Aplastic anemia can be mild, moderate, severe, or very severe.
Moderate aplastic anemia (MAA) is the classification for those who have significantly reduced blood counts but not as reduced as occurs in severe or very severe aplastic anemia. In many cases of MAA, doctors will simply monitor blood counts, which may remain unchanged for many years.
Severe aplastic anemia (SAA) is defined by a bone marrow cellularity of less than 25% and at least two of the following:
  • absolute neutrophil count (ANC) less than 500 per microliter (<500/ÁL)
  • absolute reticulocyte count (ARC) less than 20 thousand per microliter (<20,000/ÁL)
  • platelet count less than 20 thousand per microliter (<20,000/ÁL)
Very severe aplastic anemia (VSAA) is defined by an ANC less than 200 per microliter (<200/ÁL).
See also the descriptions of acquired aplastic anemia and hereditary aplastic anemia in the "Causes and Risk Factors" section above.
Treatment of Aplastic Anemia
The choice of treatment for aplastic anemia depends on the severity of the disease and the age of the patient. The more you learn about the choices, the better you will be able to be a partner with your doctor in making treatment decisions. Mild or moderate aplastic anemia is serious but usually doesn't require hospitalization. Doctors will often check blood counts regularly to watch for signs the disease is getting worse. Severe or very severe aplastic anemia is life-threatening and requires immediate hospitalization for treatment.
Dr. Neal Young of the National Institutes of Health's National Heart, Lung, and Blood Institute reminds us that only decades ago aplastic anemia patients had little hope of survival. "Now", Dr. Young says, "the great majority of platients with aplastic anemia can be effectively treated" (see video). An estimated 70% to 90% of patients can be treated successfully, but it is important to remember that statistics are only indicators; all patients react to their illness and treatment differently. The likely course of the disease will vary greatly depending on the specific circumstances of a particular patient.
Aplastic anemia cannot be corrected through dietary changes or supplements because patients do not have healthy bone marrow capable of producing properly functioning blood cells. However, a good diet is always important. Doctors may recommend dietary changes and supplements to lessen symptoms that result from aplastic anemia. Talk to your doctor before taking any supplement, including herbal supplements.
Current treatment options include:
  • watch and wait — supportive care
  • blood or platelets transfusions
  • growth factors
  • drugs for immunosuppression
  • bone marrow, stem cell, and cord blood transplants
Watch and Wait — Supportive Care
If you have only mild/tolerable symptoms, your doctor may recommend a watch and wait strategy or supportive care to manage or lessen symptoms rather than try to slow or stop the course of the disease itself. Monitoring your symptoms, performing tests on a regular basis, and giving you transfusions, antibiotics, and other treatment only as needed may be sufficient. Watch and wait is a conscious decision to avoid making things worse when you are living a mostly normal life.
Long-term treatment with transfusions is not recommended because frequent red-cell transfusions can lead to iron overload, a serious condition in which the buildup of iron in the blood can damage key organs such as the heart and liver. Iron can be removed with drugs called chelators (trade names Desferal and Exjade) but they can be difficult to administer and hard to tolerate.
Immunosuppressive Drug Therapy
The generally accepted thinking about aplastic anemia is that the patient's own immune system is reacting against the bone marrow, interfering with its ability to make blood cells. For this reason, immunosuppressive drugs are believed to counteract the problem by reducing the immune system's response, allowing the bone marrow to grow back and make blood cells again.
Immunosuppressive drug therapy is considered the standard initial treatment for adults and for all patients without a matched related donor for bone marrow or stem cell transplant. The treatment usually requires only a few days in the hospital and is generally well tolerated. Response rates, defined by the patient becoming transfusion-independent and risk-free from infection, are 70% to 80%.
The immunosuppressive drugs most commonly used to treat aplastic anemia are antithymocyte globulin (ATG) or antilymphocyte globulin (ALG), in combination with cyclosporine.
ATG is developed by injecting a horse or rabbit with human white blood cells, causing the animal's immune system to make antibodies that can be collected and purified into a serum called horse ATG (h-atg) or rabbit ATG (r-atg). Study results announced in December 2010 1 2 3 4 showed that horse ATG given as a first treatment for SAA has a statistical edge over rabbit ATG in producing a response. ATG treatment can be given more than once if there is no response or if the patient relapses. Researchers continue to study the horse-vs.-rabbit choice for repeated ATG.
Growth Factors
The proteins or hormones called growth factors are normal body products that stimulate the production of blood cells. Although most people with aplastic anemia already have unusually high levels of growth factors in their blood, very high medicinal doses can sometimes help the bone marrow work better.
  • Erythropoietin ("EPO" for short, trade names Aranesp, Epogen, and Procit) is a growth factor that boosts red blood cell production.
  • G-CSF (granulocyte colony-stimulating factor) like filgrastim (trade names include Neupogen) can boost white blood cell counts.
  • GM-CSF (granulocyte macrophage colony-stimulating factor) like sargramostim (trade names include Leukine) can also boost white blood cell counts.
It is important to remember that growth factors may help damaged bone marrow to work better but they do not cure aplastic anemia. Growth factors help support the patient by increasing blood counts until other treatments have a chance to reverse the processes causing the marrow damage.
Bone Marrow, Stem Cell, and Cord Blood Transplants
Currently, the only option for curing aplastic anemia is an allogeneic transplant using bone marrow, stem cells, or cord blood. "Allogeneic" means that the cells come from someone other than the patient. The patient receives bone marrow or stem cells from a family member, unrelated donor, or cord blood unit. In a successful transplant, defective stem cells in the patient's bone marrow are eliminated and new cells from the donor engraft (begin to function in the recipient's marrow) and produce normal blood cells.
The major risks are rejection of the transplant, mortality during the transplant process (while waiting for engraftment the patient may have no immune system), and graft-versus-host disease (GVHD or GVH). GVHD is an acute or chronic condition in which the patient's new immune system tries to reject his or her own tissue. On average, transplants have the highest rates of success for children.
Standard transplants begin with chemotherapy and radiation to destroy diseased cells, while mini transplants (non-myeloablative transplants) use lesser or no chemotherapy or radiation, making them more suitable for older patients or those with other health problems for whom the standard transplant conditioning would be unsuitable. Mini transplants may shorten recovery time but have higher relapse rates, or change the balance of risks and benefits in other ways.
To increase the likelihood of a successful transplant and minimize potential complications, the patient needs a donor with a matching tissue type. Human leukocyte antigen (HLA) typing, which looks at proteins on the surface of cells, is used to match patients and donors. This is not the same as testing your blood type; donors don't have to match your blood type.
Many patients find HLA matches among their brothers, sisters, or other close relatives (an identical twin sibling is the ideal donor), but as many as 70% of patients must search for an unrelated donor or cord blood unit. Doctors can search for donors on behalf of their patients in the Be The Match Registry operated by the National Marrow Donor Program (NMDP). A MUD transplant is one from a "matched unrelated donor."
Transplants involving partially matched (called "mismatched") donors are also possible, depending on the type of mismatch, but such transplants are riskier.
Because it can take time to identify a donor, it is a good idea to explore the possibilities in the patient's family and/or bone marrow registries as soon as aplastic anemia is diagnosed.
Clinical Trials
A clinical trial is a study conducted to evaluate a promising new treatment or to continue to learn about a current successful treatment.
Each study is designed to answer scientific questions and to find new and better ways to help patients. Clinical trials are important because the research data they provide is the route to safer and more effective treatments for all patients.
Clinical trials involve some risk because the treatments used are less proven than standard treatments. However, they offer some of the best medical care available, provide both the latest and best medical expertise, and patients receive close attention and monitoring. In addition, trials offer consistency in treatment protocols and quality controls that might vary in other settings.
Usually, clinical trials are free-of-charge for the patient, with some facilities even financing travel expenses. Most insurance companies cover treatment received in a clinical trial. Patients should consider participating in a clinical trial only after their doctor has explained the trial's specific purposes, risks, and benefits.
To learn more about clinical trials for aplastic anemia in the U.S., visit ClinicalTrials.gov or call 888-346-3656. Other excellent resources for information about clinical trials include:
Coping with Aplastic Anemia
Following a diagnosis of aplastic anemia, patients may feel shocked, scared, angry, or even relieved that they finally have a "name" for their condition. Newly diagnosed patients often describe being overwhelmed by trying to understand what aplastic anemia is and how it can be treated at the same time family and work responsibilities continue.
Here are some steps that will help you feel more in control of your situation:
  • Find a hematologist who is an expert in treating aplastic anemia. Get a referral from your primary care physician or insurance company. You can also use the Marrowforums Treatment Center Map to find treatment centers in North America.
  • Request information from the Aplastic Anemia & MDS International Foundation (AA&MDSIF). Visit their Online Learning Center. Attend their conferences. If you'd like to talk to another patient or caregiver, ask to speak to one of their Peer Support Network volunteers.
  • Contact national patient or support organizations in your country, such as the Aplastic Anemia & Myelodysplasia Association of Canada.
  • Learn as much as you can about aplastic anemia and its treatments. Learning the basic terminology of aplastia anemia will help you understand what you read and communicate with your doctor.
  • Keep track of all of your medical information, including symptoms, tests and their results, treatments (including transfusions received), an up-to-date list of your medications, and contact phone numbers, in one place. A computer, a three-ring binder, or even a folder of papers will work; just keep everything together.
  • Be an active participant in your care by asking questions of your doctors until you understand the answers, discussing information you collect, and speaking up about anything that concerns you. Bring a written list of questions to each appointment.
  • If possible, have a family member or close friend accompany you to medical appointments. They can help you listen, take notes, and make sure you remember to ask your questions.
  • Get a second opinion. No reputable doctor will object to your confirming your diagnosis and treatment recommendations with another specialist.
  • Take advantage of services offered at your treatment center (counselors and social workers, language translators, etc.), support groups in your city, wellness programs of your insurance company, neighborhood support groups, and support offered by religious groups, even if these services aren't specific to bone marrow failure diseases.
  • Keep in regular touch with family, friends, and the others closest to you. Don't let relationships falter just because your situation has changed.
  • Talk to other patients in the Marrowforums discussion forums.
  • Visit other sites, such as Aplastic Anemia Central, that have information or discussion areas specific to aplastic anemia.
We hope that after reading this page you will participate in the discussions at Marrowforums and continue to learn about aplastic anemia through the experiences of patients, family members, and caregivers who exchange help and support 24 hours a day, every day of the year.