Aplastic Anemia

Aplastic anemia is a rare but serious blood disorder. If you have it, your bone marrow doesn't make enough new blood cells. Causes include

• Being exposed to toxic substances, such as pesticides, arsenic, and benzene
• Radiation therapy and chemotherapy for cancer
• Certain medicines
• Infections such as hepatitis, Epstein-Barr virus, or HIV
• Autoimmune disorders
• Certain inherited conditions

In many people, the cause is unknown.

Aplastic anemia

Your doctor will diagnose aplastic anemia based on your medical and family histories, a physical exam, and test results. Once your doctor knows the cause and severity of the condition, he or she can create a treatment plan for you. Treatments include blood transfusions, blood and marrow stem cell transplants, and medicines.

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.

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 include FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, and FANCN. 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 symptom of FA. In some cases though, the child will look completely normal. People with FA can start to have low blood counts at a very early age. The low blood counts may be treated with medications called androgens at first, but only a bone marrow 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 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 (called 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 calledtelomeres. 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. Symptoms 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.

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 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 or exposure to a toxic chemical. 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 called hemolysis). 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 get PNH. PNH can be treated with bone marrow transplant or with a drug called eculizumab that blocks the hemolysis.