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Aplastic Anemia

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What is Aplastic Anemia?

Aplastic anemia is a disorder in which the bone marrow fails to make enough blood cells. The bone marrow is the soft, inner part of bones where the 3 types of blood cells are made:

Red blood cells, which carry oxygen to the tissues from the lungs

White blood cells, which fight infection

Platelets, which seal damaged blood vessels to prevent bleeding

These cells are made by blood-forming stem cells in the bone marrow. In aplastic anemia, the stem cells are damaged and there are very few of them. As a result, too few blood cells are produced. In most cases of aplastic anemia, all 3 types of blood cells are low (which is called pancytopenia). Rarely, just one of the cell lines, such as red cells, white cells, or platelets, is abnormal.

Red blood cells, which carry oxygen to the tissues from the lungs

White blood cells, which fight infection

Platelets, which seal damaged blood vessels to prevent bleeding

These cells are made by blood-forming stem cells in the bone marrow. In aplastic anemia, the stem cells are damaged and there are very few of them. As a result, too few blood cells are produced. In most cases of aplastic anemia, all 3 types of blood cells are low (which is called pancytopenia). Rarely, just one of the cell lines, such as red cells, white cells, or platelets, is abnormal.

Aplastic anemia is not a type of cancer but may be associated with certain cancers (especially those affecting the bone marrow, such as leukemia) or cancer treatments. A small number of patients with aplastic anemia may develop leukemia.

Aplastic anemia can be inherited or acquired. Acquired aplastic anemia is much more common than the inherited type.

Inherited aplastic anemia

Aplastic anemia is considered inherited when it is caused by gene mutations (abnormal copies of genes) that have been passed on from the parents to their child. Inherited aplastic anemia is more common in children and young adults.

Fanconi anemia: The most common cause of inherited aplastic anemia is called Fanconi anemia (FA). There are many different genes that can cause Fanconi anemia. They are named FANC plus another letter (or a letter and a number), such asFANCA, FANCB, FANCC, etc. In order to get FA, a child must inherit 2 abnormal copies of one of these genes -- one from each parent. Someone with only one abnormal copy will not develop the disease and is called a carrier.

The genetic material (DNA) in our cells is packaged into chromosomes. In FA, the chromosomes are easily damaged by things in the environment like toxins or radiation. This can lead to aplastic anemia, leukemia, and other cancers. Cancers of the mouth and throat, esophagus, and the vulva (female genital area) are seen at a higher rate and at a younger age in those with FA (as compared with people who don’t have FA).

In many cases, FA is suspected when a child is born because he or she is missing a thumb or a bone in the arm called the radius. A child with FA anemia also may not grow well (called growth retardation) or have a small head (called microcephaly). Dark spots on the skin (called café au lait spots) can be another sign of FA. In some cases though, the child will look completely normal. People with FA may have low blood counts from an early age. The low blood counts may be treated with medications called androgens at first, but only a stem cell transplant can actually cure aplastic anemia in someone with FA.

Some people with FA do not develop low blood counts (or aplastic anemia), but may first be diagnosed with FA when they get cancer.

In order to diagnose FA anemia, a chromosome breakage test will be ordered. For this test, a small sample of blood is taken from the patient. Then some of the cells in the blood (the lymphocytes) are exposed to a certain chemical to see if it causes the chromosomes in the cells to break and rearrange. Chromosomes in normal cells aren’t damaged easily, but the chromosomes in FA cells will be damaged.

Dyskeratosis congenita: Another inherited cause of aplastic anemia is called dyskeratosis congenita (DC). Defects in some of the genes that help protect the chromosomes cause this disease. The chromosomes in our cells are fitted with caps at each end called telomeres. These caps help protect the ends of the chromosomes from being damaged. Telomerase is the protein that maintains the telomeres. Two different genes, called TERC and TERT, are needed to make telomerase. An abnormal copy of either one of these genes can cause DC. Another gene, DKC1, makes a protein called dyskerin that is needed for telomerase to work. Abnormalities in this gene also cause DC. Signs of this disorder include abnormal skin pigmentation, abnormal nails, and white patches in the mouth (called leukoplakia). People with this problem have a high risk of developing aplastic anemia and certain cancers, such as cancer of the mouth and throat and cancer of the anus. Some people are only diagnosed with DC when they come in with aplastic anemia and are found to have abnormal telomerase genes. These people may not have any of the other signs or symptoms of DC.

Other causes of inherited aplastic anemia

Another cause of inherited aplastic anemia is called the Diamond-Blackfan syndrome. In this disease, red blood cells are low, but the number of other blood cells is normal. Patients with Diamond-Blackfan syndrome also have an increased risk of certain cancers, including myelodysplastic syndrome, leukemia, colon cancer, and bone cancer.

A fourth disorder is the Shwachman-Diamond syndrome, which is caused by abnormal copies of a gene called SDS. Here, the major problem is poor production of white blood cells, although the other cell lines can also be abnormal. In both of these, patients will often have other problems such as short stature and other bone abnormalities.

Acquired aplastic anemia: Acquired aplastic anemia usually occurs in adults, but children may also be affected. Most have no gene abnormalities. Scientists have found that some of the people who they thought had a form of acquired aplastic anemia actually have an abnormality in one of the genes responsible for inherited aplastic anemia. The aplastic anemia in these people is not really acquired -- it is inherited. Some cases of aplastic anemia seem to be triggered by a drug, exposure to a toxic chemical, or infection with some types of viruses. In most cases of aplastic anemia, however, the cause is never found.

Paroxysmal nocturnal hemoglobinuria: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease in which some of the stem cells in the bone marrow become damaged and make abnormal red blood cells. The red blood cells in PNH are missing certain proteins that normally help protect the cells. Without these proteins, the red blood cells are killed by the immune system (this is calledhemolysis). PNH is caused when the gene called PIG-A is damaged (mutated) in some of the stem cells in the bone marrow. People with PNH have anemia (low red blood cells) along with fatigue, stomach pain, and blood clots. Sometimes the hemoglobin from the destroyed red blood cells will cause the urine to become very dark (like the color of tea). PNH seems to be linked to aplastic anemia. Some patients have small numbers of PNH cells when they are diagnosed with aplastic anemia. Also, some survivors of aplastic anemia will go on to develop PNH. PNH can be treated with stem cell transplant or with a drug called eculizumab that blocks the hemolysis.

Risk Factors

A risk factor is anything that changes your chance of getting a disease. For example, certain cancers have different risk factors. Exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for many cancers. But risk factors don’t tell us everything. Having a risk factor, or even several, does not mean that you will get the disease. And not having a risk factor doesn’t mean that you won’t get the disease.

We know that certain aplastic anemias are inherited. Having Fanconi anemia or dyskeratosis congenita increases the risk of developing aplastic anemia.

Exposure to certain drugs and chemicals may increase the risk of acquired aplastic anemia. It’s important to realize that these medications are safe for most of the people who take them. In some cases, however, people develop aplastic anemia after receiving one of these drugs. Likewise, some viruses are linked to acquired aplastic anemia, but aplastic anemia develops only in a very small percentage of people with these infections.

Medicines: Some of the medicines linked to aplastic anemia include:

Nonsteroidal anti-inflammatory drugs (NSAIDs) -- medicines used to treat pain and inflammation. Examples include indomethacin (Indocin®), piroxicam (Feldene®), and diclofenac (Voltaren®)

Amphetamines, including MDMA (Ectasy)

Antibiotics, including sulfonamides (“sulfa drugs”) and forms of penicillin

Anti-thyroid drugs, such as propylthiouracil and methimazole (Tapazole®)

Carbonic anhydrase inhibitors, including acetazolamide and methazolamide (these are used to treat glaucoma)

Diabetes medications, including tolbutamide, carbutamide, and chlorpropamide

Diuretics (water pills), such as furosemide (Lasix®) and thiazides

Drugs used against malaria, including quinacrine and chloroquine

Phenothiazines (Thorazine®, Compazine®) -- medicines used for nausea and certain psychiatric problems

Allopurinol (Zyloprim®) -- used for treating gout

Ticlopidine -- used to prevent strokes and heart attacks

Anti-seizure drugs like carbemazepine (Tegretol®), phenytoin (Dilantin®), and valproic acid

Chloramphenicol, an antibiotic (no longer available in the United States)

Mesalazine which is used to treat ulcerative colitis and Crohns disease

This is only a partial list of the drugs most often associated with aplastic anemia. Other drugs may also cause this disease. The best way to avoid aplastic anemia from drugs is to take medicines only if they are necessary.

Chemicals: Exposure to chemicals such as solvents and pesticides at home or in the workplace is also a risk factor. These include:

Benzene, which is found in gasoline, automobile exhaust fumes, cigarette smoke, emissions from coke ovens and other industrial processes, and waste water from certain industries, is the most common offender.

Industrial pesticides, like organophosphates and carbamates

Other risk factors: Other conditions have been linked to aplastic anemia, such as:


Viruses such as Epstein-Barr virus, cytomegalovirus (CMV), parvovirus B19, and HIV.


Auto-immune diseases like lupus (systemic lupus erythematosus) and rheumatoid arthritis

Severe radiation poisoning (as seen after an atomic bomb explosion)

Do we know what causes aplastic anemia?

Most cases of acquired aplastic anemia have no known cause. In rare cases, the cause is exposure to certain chemicals such as benzene. Although many chemotherapy drugs and radiation treatment can damage the bone marrow, they don’t usually cause aplastic anemia. When a cause can be found, it is most often a drug or a viral infection. Environmental pollutants are another possible cause.

Doctors have tried to figure out how medicines, chemicals, and viruses can cause this disease. The most commonly accepted explanation is that these agents trigger an abnormal immune reaction in the body of some people. In this reaction, a type of immune cell called the T-cell (or T-lymphocyte) starts making too much of certain substances called cytokines. These cytokines are toxic to bone marrow cells and can cause them to die.

Signs and symptoms of aplastic anemia

If you have aplastic anemia, you may have some of the following problems:

Feeling very tired (fatigued) and short of breath, which is caused by anemia (too few red blood cells). People with anemia also tend to be pale.

Problems with infections that keep coming back or are severe (even life-threatening). This is caused by not having enough infection-fighting white blood cells (called neutropenia/leukopenia)

Abnormal bruising or bleeding because of a shortage of platelets (thrombocytopenia)

Some people may not have any symptoms, but results of a routine blood test may suggest a diagnosis of aplastic anemia. There are other conditions in which blood formation may be abnormal. Your doctor will consider all of these when determining your diagnosis.


Tests to diagnose aplastic anemia: Two main tests are used to diagnose aplastic anemia.

Complete blood count (commonly called a CBC). In aplastic anemia this test will show that the red cell count, white cell count, and platelet count are low.

Bone marrow biopsy. This test looks at the bone marrow, which contains the blood-forming cells.

Complete blood count: The complete blood count (CBC) is a test that measures the different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. This test is done on a sample of blood, usually taken from a vein in your arm.

If this test shows that your blood counts are low, other tests may be done to look for the cause. Often the levels of vitamins (like vitamin B12 and folate) and iron will be checked to be sure that low levels aren’t causing the low blood counts. Poor kidney function can sometimes cause anemia, so blood chemistry tests are often checked as well.

If these tests do not find an underlying cause of the low blood counts, you will need to have a bone marrow biopsy.

Bone marrow biopsy: A bone marrow biopsy has 2 parts: the aspiration and the biopsy. This procedure is usually done while you are lying on your stomach. A part of the pelvic bone (located about 2 inches to the side of the spine) and the skin above it are numbed with local anesthetic. A tiny cut (about 1/8 inch) may be made in the skin to make it easier to insert the needle. Then, for the aspiration, a large needle is placed through the incision into the bone. A syringe is used to remove a small amount of liquid bone marrow (about 1 teaspoon). Even with the numbing medicine, this often causes a brief, sharp pain.

For the biopsy, the needle is repositioned and used to remove a small cylinder-shaped piece of bone and marrow (about 1/16 inch in diameter and 1/3 inch long). Both samples usually are taken during the same procedure from the same place in the back of the pelvic (hip) bone. In spite of local anesthesia, this procedure may still be uncomfortable.

A pathologist, a doctor specializing in diagnosing disease by lab tests, examines the bone marrow under a microscope. A hematologist (internist who specializes in blood diseases) or a hematopathologist (a pathologist who specializes in blood diseases) might also look at the bone marrow sample. Normally, the bone marrow contains many cells that produce the different types of blood cells. Finding an “empty” bone marrow -- that is, one that lacks normal blood-producing cells -- confirms the diagnosis of aplastic anemia. Leukemia or other kinds of cancers can also cause low blood counts, but in that case the bone marrow would be filled with leukemia cells or other cancer cells.

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