Aplastic anemia is a rare and serious disorder that affecst the bone marrow and blood. Bone marrow is the soft, spongelike tissue inside the bones. Bone marrow makes stem cells that develop into one of the three types of blood cells—red blood cells, white blood cells, or platelets. Red blood cells contain hemoglobin, an iron-rich protein that gives blood its red color and carries oxygen from the lungs to all parts of the body. White blood cells help the body fight infections. Platelets are blood cell fragments that stick together to seal small cuts or breaks on blood vessel walls and stop bleeding.
In aplastic anemia, the bone marrow is hypocellular and does not produce enough healthy red or white blood cells or platelets. Too few functioning red and white blood cells can lead to fatigue and infection. Too few platelets can lead to spontaneous or uncontrolled bleeding. The term "aplastic anemia" is somewhat of a misnomer because all three cell lines, noto just the red blood cells, but also the white blood cells and platelets can be deficient.
Anemia most often describes a condition in which the number of red blood cells is less than normal, resulting in less oxygen carried to the body's cells. In aplastic anemia, however, normal production of all blood cells slows or stops. Blood cell production declines because bone marrow stem cells are damaged. The number of stem cells also declines because they are unable to replicate themselves. Although production of mature blood cells is seriously impaired in aplastic anemia, the few blood cells that mature and enter the bloodstream are normal.
A somewhat similar disorder is myelodysplasia (MDS). In MDS, a shortage of bone marrow stem cells usually does not occur, as it does in aplastic anemia. However, the stem cells are defective and do not mature normally. Progenitor cells and immature blood cells are deformed and fail to develop into healthy, mature red or white blood cells or platelets. These cells often die in the bone marrow. Many of the blood cells that do enter the bloodstream do not survive or function normally. Some forms of MDS are prone to develop into leukemia, an aggressive blood cancer.
Young adults ages 20 to 25 years and people older than 60 years are most likely to have aplastic anemia. Men and women are equally affected. Most new cases in children are due to inherited bone marrow failure syndromes, caused by abnormal chromosomes. About four out of every 1 million people in the United States get aplastic anemia each year.
What Causes Aplastic Anemia?
Although a cause is not found in most cases of aplastic anemia, the diseases may be triggered by exposure to chemotherapy, radiation therapy, high levels of ionizing radiation (the type produced by high-power x-ray machines and in nuclear power plants), benzene, toxic chemicals in some pesticides, and certain viral infections. In most cases of aplastic anemia, these triggers, or other unknown causes, provoke the body's own immune system to destroy the bone marrow stem cells. Certain rare, inherited bone marrow failure syndromes can also lead to aplastic anemia.
What are the symptoms of Aplastic Anemia?
Symptoms may include fatigue, weakness, excessive bleeding, such as from external injuries or operations, pinpoint red spots on the skin caused by bleeding from small blood vessels, easy bruising, frequent infections, fevers, pale skin, and shortness of breath.
Symptoms vary depending on the person and the severity and type of disease.
How is Aplastic Anemia Diagnosed?
In addition to a medical history and physical exam, health care providers use blood tests, a bone marrow biopsy, and cytogenic analysis to diagnose aplastic anemia. A health care provider may refer a person to a hematologist—a doctor who treats diseases or disorders of the blood. A person also may be referred to an oncologist—a doctor who treats cancer—because aplastic may be related to bone marrow cancers.
Blood tests. A blood test involves drawing a person's blood at a health care provider's office or a commercial facility and sending the sample to a lab for analysis. A complete blood count is usually the first test a health care provider uses to detect aplastic anemia. The test includes measurement of a person's hematocrit, the percentage of the blood that consists of red blood cells. A complete blood count also measures the amount of hemoglobin in the blood, whether a person has a lower-than-normal number of red blood cells, whether a person has enough iron, and the number of white blood cells and platelets in the blood.
Lower-than-normal numbers of one or more blood cell types may suggest aplastic anemia.
In another test called a peripheral blood smear, the health care provider examines a sample of blood with a microscope for unusual changes in the size, shape, and appearance of the blood cells. These cells usually appear normal in aplastic anemia.
A health care provider also may order blood tests to check for a shortage of folate, vitamin B12, and erythropoietin—a hormone made in the kidneys that stimulates the production of red blood cells.
Bone marrow biopsy. A health care provider needs results from a bone marrow biopsy to confirm the diagnosis of aplastic anemia. A biopsy is a procedure that involves taking a small piece of bone marrow, blood, and a small piece of bone for examination with a microscope. A health care provider performs the biopsy during an office visit or in a hospital and uses light sedation and local anesthetic. During the biopsy, the health care provider inserts a needle into the hip bone or breastbone. A pathologist—a doctor who specializes in diagnosing diseases—analyzes the bone marrow samples in a lab. The test can show abnormal cells, the number and type of blood progenitor cells, and levels of iron in the bone marrow.
Cytogenic analysis. This test involves sending the person's bone marrow samples from the biopsy to a lab where a pathologist examines them with a microscope to look for abnormal changes in the person's chromosomes.
How is Aplastic Anemia Treated?
People with mild or moderate aplastic anemia may not need treatment at first. However, people with severe aplastic anemia need immediate medical treatment to prevent or reverse complications from having low blood cell levels. Treatment options, which a health care provider may use alone or in combination, include blood and bone marrow stem cell transplants, which require chemotherapy and radiation therapy, medications, and blood transfusions.
Treatment options depend on the age and general health of the person and the severity of the disease.
Blood and bone marrow stem cell transplants. Blood and bone marrow stem cell transplants, also called stem cell transplants, replace damaged stem cells in bone marrow with healthy stem cells from a donor's blood or bone marrow and can cure aplastic anemia. Treatment guidelines state that stem cell transplant is the best treatment for people younger than 40 who have an available donor whose blood and bone marrow cells have been tested and found to "match" those of the patient. Stem cell transplants (SCT) in people older than 40 are possible; however, long-term survival rates are lower. Older adults are generally less able to tolerate the treatments used to prepare the body for transplant and are more likely to develop severe posttransplant complications.
A health care provider confirms a matching donor by using a blood test called human leukocyte antigen (HLA) tissue typing. Human leukocyte antigens are proteins found on the surface of white blood cells.
If health care providers do not find a matching donor in a person's family, they will search the National Marrow Donor Program to look for other sources of stem cells for a transplant. Millions of volunteer donors are registered to provide a potential match. Health care providers look for donors who are a match and not family members, family members who are close matches, although not exact, unrelated donors who are close matches, although not exact, and umbilical cord blood that is a match.
Umbilical cord blood collected from an umbilical cord and a placenta after a baby is born is frozen and stored at a cord blood bank for future use. Some people donate umbilical cord blood to a public cord blood bank, while others pay to store it at a private bank.
Before the transplant, a health care provider uses chemotherapy and sometimes radiation therapy to destroy a person's own damaged bone marrow cells. These therapies also suppress a person's immune system to prevent it from attacking the new stem cells after the transplant.
Chemotherapy and Radiation Therapy
Chemotherapy. Chemotherapy is a treatment that uses medications to stop the growth of immature blood cells, either by killing the cells or stopping them from dividing. A person can take chemotherapy medications by mouth or have them injected into cerebrospinal fluid or a vein, a muscle, an organ, or a body cavity, such as the abdomen. High doses can cause side effects such as nausea, vomiting, diarrhea, and fatigue. Treatment takes place in a hospital or chemotherapy treatment center. People may take oral chemotherapy medications at home. A team of health care providers, such as an oncologist and an oncology nurse, cares for people undergoing chemotherapy. A patient does not need anesthesia.
Radiation therapy. Radiation therapy is a treatment that uses external beams of either small doses of radiation over a period of time or a single, precise, high dose of radiation. Treatment takes place in a hospital or radiation treatment center. A team of health care providers, including a radiation oncologist—a doctor who specializes in treating tumors or cancer with radiation—cares for people receiving radiation therapy. Most people cannot feel radiation and do not require anesthesia. Side effects may include fatigue and skin sensitivity around the area being treated.
In a hospital, health care providers remove stem cells from the donor and freeze them for storage. If the donor stem cells are coming from the blood, the blood is removed from a large vein in the donor's arm or through a central venous catheter, a flexible tube that is placed in a large vein in the neck, chest, or groin area. The blood goes through a machine that removes the stem cells. The blood is then returned to the donor and the health care provider stores the collected cells. If the donor stem cells are coming from the bone marrow, the health care provider will insert a hollow needle into the donor's pelvis to withdraw the marrow. This procedure occurs in a hospital with local or general anesthesia and is less common.
After receiving chemotherapy or radiation therapy, a person receives the thawed donor stem cells through an intravenous (IV) line, a needle in a vein, or a central venous catheter. The stem cells then travel to the bone marrow where they re-establish and maintain normal blood cell production. The person may be given medication to relax. The transplant will take an hour or longer to complete. The catheter will stay in place for at least 6 months after the transplant, and the person will stay in the hospital from several weeks to months to ensure the transplant is successful. During this time, a person may easily develop an infection due to a weak immune system.
Stem cell transplants carry risks. A person's immune system may attack the donated stem cells, called graft failure. Donated stem cells can attack the recipient's body, called graft-versus-host disease. Both of these complications can be life threatening.
Read more in Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation at www.cancer.gov .
Medications. Health care providers often prescribe one or more immunosuppressive medications, which suppress the immune system and reduce damage to bone marrow cells. Medications such as antithymocyte globulin may let the marrow start making blood cells again and reduce or eliminate the need for transfusions. In some people, blood counts return to normal. These medications are the preferred form of treatment for adults with severe aplastic anemia older than 40, younger patients who do not have a matched stem cell donor, and people with aplastic anemia who depend on blood transfusions.Taking these medications alone usually does not result in a cure. Health care providers often prescribe corticosteroid medications to limit the side effects of immunosuppressants such as antithymocyte globulin and cyclosporine.
A person also may be given a man-made version of erythropoietin or a growth factor therapy that stimulates white blood cell production.
If infections due to low white blood cell counts occur, a health care provider may give the patient medications to kill bacteria, fungi, or viruses.
Health care providers often treat people with mild, inherited forms of aplastic anemia with man-made forms of androgens—male sex hormones that stimulate blood production. Androgens can help improve blood counts; however, they are not a cure.
Blood transfusions. A blood transfusion is a procedure in which a person receives healthy blood cells from a donor with the same blood type through an IV line. A health care provider performs the procedure during an office visit or in a hospital. The procedure lasts 1 to 4 hours, depending on how much blood the patient needs. Transfusions of red blood cells or platelets can raise blood cell counts and relieve symptoms. Transfusions are not a cure.
Most people with aplastic anemia need repeated transfusions, which can lead to complications. Over time, the body may develop antibodies that damage or destroy donor blood cells. Iron from transfused red blood cells can build up in the body and damage organs unless the health care provider prescribes medications called iron chelators to remove extra iron. Health care providers avoid giving a transfusion before a blood and bone marrow stem cell transplant because it increases the chances that the transplant will fail.
Supportive care. Traditionally the first line of treatment, supportive care aims to manage the symptoms of the disease. This approach may include blood transfusions to help problems caused by low blood cells counts, such as fatigue and infections, and may also include growth factor therapy.
Medications. A health care provider may give immunosuppressive medications such as lenalidomide (Revlimid) and antithymocyte globulin with or without cyclosporine to help the bone marrow function more normally. A person may need an iron chelator to treat too much iron in the blood. Some people also may benefit from erythropoietin. A health care provider may also give medications to fight infections with bacteria, fungi, or viruses.
Chemotherapy. A health care provider may give chemotherapy in an effort to destroy defective blood progenitor cells and let the few remaining normal blood stem cells re-establish normal blood cell production. Chemotherapy medications may include azacitidine (Vidaza), decitabine (Dacogen), or other anticancer medications. This approach is often not effective over the long term. A health care provider may also use chemotherapy prior to stem cell transplants.
Blood and bone marrow stem cell transplants. In the past, only a stem cell transplant with a matched sibling donor offered a cure for aplastic anemia. However, experts have made much progress with transplants from unrelated matched donors, including unrelated umbilical cord blood transplantation. In the past, health care providers did not routinely perform blood and bone marrow stem cell transplants for older adults. However, health care providers who are using newer techniques that use a less toxic pre-transplant regimen are performing successful blood and bone marrow stem cell transplants in this age group.
Reduced-intensity stem cell transplant (Mini-SCT)
An alternative option for older individuals that may not be able to tolerate the intensive pre-treatment with radiation and chemotherapy that a conventional SCT requires, is what has been called a "mini"-SCT. Mini-transplant patients are pre-treated with lower doses of chemotherapy, generally without radiation therapy, which they tolerate better. They then receive an infusion of donor stem cells from a compatible donor, which reconstitute the bone marrow with healthy stem cells that give rise to normal red blood cells, white blood cells, and platelets.
Mini-SCT has been successfully used to treat aplastic anemia, leukemia, myelodysplasia, myeloproliferative diseases, lymphoma, and multiple myeloma. Unlike conventional SCT, which essentially eliminates all lthe stem cells in the bone marrow, mini-SCT suppresses the bone marrow to allow healthy donor stem cells to reconstitute the bone marrow.
While there are still significant risks with the mini-SCT, it is an option for older patients that may not tolerate conventional bone marrow therapy.
Disability Benefits with Aplastic Anemia
Whether you are eligible for long-term disability benefits under the Social Security Act (SSDI) and/or in accordance with an employer-based disability plan (ERISA), will depend on the stage of your aplastic anemia, the symptoms and functional limitations that you have, and the adequacy of the medical documentation in your medical record. Remember, that aplastic anemia is a bone marrow condition that not only affects red blood cells and causes "anemia," but that it also can affect white blood cells and platelets. (In that respect, the term "aplastic anemia" is somewhat of a misnomer.)
If you have aplastic anemia (just like with MDS) and suffer from chronic anemia, with a hemoglobin level <10, and have tiredness, severe fatigue, weakness, light-headedness, and other related symptoms, your functional capacity may be "less than sedentary" (meaning you are unable to perform even a "desk job"), and your chances of a long-term disability benefit award should be favorable. If you are prone to repeated infections, by virtue of a low white blood cell count, then certain working environments (crowds, multiple-person offices) may be medically contraindicated, because of the risk of exposure to infection. If you require treatment with immunosupressive drugs or chemotherapy, side effects from those drugs may also restrict your ability to work.