APLASTIC ANEMIA DEFINITION
Aplastic anemia is a condition that occurs when your body stops producing enough new blood cells. Aplastic anemia leaves you feeling fatigued and with a higher risk of infections and uncontrolled bleeding.
A rare and serious condition, aplastic anemia can develop at any age. Aplastic anemia may occur suddenly, or it can occur slowly and get worse over a long period of time. Treatment for aplastic anemia may include medications, blood transfusions or a stem cell transplant.
APLASTIC ANEMIA CAUSES
Damage to the bone marrow’s stem cells causes aplastic anemia. When stem cells are damaged, they don’t grow into healthy blood cells.
The cause of the damage can be acquired or inherited. “Acquired” means you aren’t born with the condition, but you develop it. “Inherited” means your parents passed the gene for the condition on to you.
Acquired aplastic anemia is more common, and sometimes it’s only temporary. Inherited aplastic anemia is rare.
In many people who have aplastic anemia, the cause is unknown. Some research suggests that stem cell damage may occur because the body’s immune system attacks its own cells by mistake.
Many diseases, conditions, and factors can cause aplastic anemia, including:
- Toxins, such as pesticides, arsenic, and benzene.
- Radiation and chemotherapy (treatments for cancer).
- Medicines, such as chloramphenicol (an antibiotic rarely used in the United States).
- Infectious diseases, such as hepatitis, Epstein-Barr virus, cytomegalovirus (si-to-MEG-ah-lo-VI-rus), parvovirus B19, and HIV.
- Autoimmune disorders, such as lupus and rheumatoid arthritis.
- Pregnancy. (Aplastic anemia that occurs during pregnancy often goes away after delivery.)
Sometimes, cancer from another part of the body can spread to the bone and cause aplastic anemia.
Certain inherited conditions can damage the stem cells and lead to aplastic anemia. Examples include Fanconi anemia, Shwachman-Diamond syndrome, dyskeratosis (DIS-ker-ah-TO-sis) congenita, and Diamond-Blackfan anemia.
APLASTIC ANEMIA PATHOPHYSIOLOGY
Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Almost universally fatal just a few decades ago, aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Immunosuppression with antithymocyte globulins and cyclosporine is effective at restoring blood-cell production in the majority of patients, but relapse and especially evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenges are extending the benefits of transplantation to patients who are older or who lack family donors. Recent results with alternative sources of stem cells and a variety of conditioning regimens to achieve their engraftment have been promising, with survival in small pediatric case series rivaling conventional transplantation results.
APLASTIC ANEMIA SYMPTOMS
Aplastic anemia symptoms may include:
- Shortness of breath with exertion
- Rapid or irregular heart rate
- Pale skin
- Frequent or prolonged infections
- Unexplained or easy bruising
- Nosebleeds and bleeding gums
- Prolonged bleeding from cuts
- Skin rash
Aplastic anemia can progress slowly over weeks or months, or it may come on suddenly. The illness may be brief, or it may become chronic. Aplastic anemia can be very severe and even fatal.
APLASTIC ANEMIA DIAGNOSIS
If your primary care doctor thinks you have aplastic anemia, he or she may refer you to a hematologist. A hematologist is a doctor who specializes in treating blood diseases and disorders.
Medical and Family Histories
Your doctor may ask questions about your medical history, such as whether:
- You’ve had anemia or a condition that can cause anemia
- You have shortness of breath, dizziness, headaches, or other signs and symptoms of anemia
- You’ve been exposed to certain toxins or medicines
- You’ve had radiation or chemotherapy (treatments for cancer)
- You’ve had infections or signs of infections, such as fever
- You bruise or bleed easily
Your doctor also may ask whether any of your family members have had anemia or other blood disorders.
Your doctor will do a physical exam to check for signs of aplastic anemia. He or she will try to find out how severe the disorder is and what’s causing it.
The exam may include checking for pale or yellowish skin and signs of bleeding or infection. Your doctor may listen to your heart and lungs for abnormal heartbeats and breathing sounds. He or she also may feel your abdomen to check the size of your liver and feel your legs for swelling.
Many tests are used to diagnose aplastic anemia. These tests help:
- Confirm a diagnosis of aplastic anemia, look for its cause, and find out how severe it is
- Rule out other conditions that may cause similar symptoms
- Check for paroxysmal nocturnal hemoglobinuria (PNH)
Complete Blood Count
Often, the first test used to diagnose aplastic anemia is a complete blood count (CBC). The CBC measures many parts of your blood.
This test checks your hemoglobin and hematocrit (hee-MAT-oh-crit) levels. Hemoglobin is an iron-rich protein in red blood cells. It carries oxygen to the body. Hematocrit is a measure of how much space red blood cells take up in your blood. A low level of hemoglobin or hematocrit is a sign of anemia.
The normal range of these levels varies in certain racial and ethnic populations. Your doctor can explain your test results to you.
The CBC also checks the number of red blood cells, white blood cells, and platelets in your blood. Abnormal results may be a sign of aplastic anemia, an infection, or another condition.
Finally, the CBC looks at mean corpuscular (kor-PUS-kyu-lar) volume (MCV). MCV is a measure of the average size of your red blood cells. The results may be a clue as to the cause of your anemia.
A reticulocyte (re-TIK-u-lo-site) count measures the number of young red blood cells in your blood. The test shows whether your bone marrow is making red blood cells at the correct rate. People who have aplastic anemia have low reticulocyte levels.
Bone Marrow Tests
Bone marrow tests show whether your bone marrow is healthy and making enough blood cells. The two bone marrow tests are aspiration (as-pi-RA-shun) and biopsy.
Bone marrow aspiration may be done to find out if and why your bone marrow isn’t making enough blood cells. For this test, your doctor removes a small amount of bone marrow fluid through a needle. The sample is looked at under a microscope to check for faulty cells.
A bone marrow biopsy may be done at the same time as an aspiration or afterward. For this test, your doctor removes a small amount of bone marrow tissue through a needle.
The tissue is checked for the number and types of cells in the bone marrow. In aplastic anemia, the bone marrow has a lower than normal number of all three types of blood cells.
Other conditions can cause symptoms similar to those of aplastic anemia. Thus, other tests may be needed to rule out those conditions. These tests may include:
- X ray, computed tomography (CT) scan, or an ultrasound imaging test. These tests can show enlarged lymph nodes in your abdomen. Enlarged lymph nodes may be a sign of blood cancer. Doctors also may use these tests to look at the kidneys and the bones in the arms and hands, which are sometimes abnormal in young people who have Fanconi anemia. This type of anemia can lead to aplastic anemia.
- Chest x ray. This test creates pictures of the structures inside your chest, such as your heart, lungs, and blood vessels. A chest x ray may be used to rule out infections.
- Liver tests and viral studies. These tests are used to check for liver diseases and viruses.
- Tests that check vitamin B12 and folate levels in the blood. These tests can help rule out anemia caused by vitamin deficiency.
Your doctor also may recommend blood tests for PNH and to check your immune system for proteins called antibodies. (Antibodies in the immune system that attack your bone marrow cells may cause aplastic anemia.)
APLASTIC ANEMIA TREATMENT
Treatments for aplastic anemia may include observation for mild cases, blood transfusions and medications for more-serious cases, and in severe cases, bone marrow transplantation. Severe aplastic anemia, in which your blood cell counts are extremely low, is life-threatening and requires immediate hospitalization for treatment.
Treatment for aplastic anemia usually involves blood transfusions to control bleeding and relieve anemia symptoms. Blood transfusions aren’t a cure for aplastic anemia. But they do relieve signs and symptoms by providing blood cells that your bone marrow isn’t producing. A transfusion may include:
- Red blood cells. Transfusions of red blood cells raise red blood cell counts. This helps relieve anemia and fatigue.
- Platelets. Transfusions of platelets help prevent excessive bleeding.
While there’s generally no limit to the number of blood cell transfusions you can have, complications can sometimes arise with multiple transfusions. Transfused red blood cells contain iron that can accumulate in your body and can damage vital organs if an iron overload isn’t treated. Medications can help your body get rid of excess iron. Another possible complication is that over time, your body may develop antibodies to transfused blood cells, making them less effective at relieving symptoms. However, the use of immunosuppressant medication makes this complication less likely.
Stem cell transplant
A stem cell transplant to rebuild the bone marrow with stem cells from a donor may offer the only successful treatment option for people with severe aplastic anemia. A stem cell transplant, which is also called a bone marrow transplant, is generally the treatment of choice for people who are younger and have a matching donor — most often a sibling.
If a donor is found, your diseased bone marrow is first depleted with radiation or chemotherapy. Healthy stem cells from the donor are filtered from the blood. The healthy stem cells are injected intravenously into your bloodstream, where they migrate to the bone marrow cavities and begin generating new blood cells. The procedure requires a lengthy hospital stay. After the transplant, you’ll receive drugs to help prevent rejection of the donated stem cells.
A stem cell transplant carries risks. There’s a chance that your body may reject the transplant, leading to life-threatening complications. In addition, not everyone is a candidate for transplantation or can find a suitable donor.
For people who can’t undergo a bone marrow transplant or for those whose aplastic anemia may be due to an autoimmune disorder, treatment may involve drugs that alter or suppress the immune system (immunosuppressants).
Drugs such as cyclosporine (Gengraf, Neoral, Sandimmune) and anti-thymocyte globulin (Thymoglobulin) are examples. These drugs suppress the activity of immune cells that are damaging your bone marrow. This helps your bone marrow recover and generate new blood cells. Cyclosporine and anti-thymocyte globulin are often used in combination.
Corticosteroids, such as methylprednisolone (Medrol, Solu-Medrol), are often given at the same time as these drugs.
Immune-suppressing drugs can be very effective at treating aplastic anemia. The downside is that these drugs further weaken your immune system. It’s also possible that after you stop taking these drugs, aplastic anemia may return.
Bone marrow stimulants
Certain drugs — including colony-stimulating factors, such as sargramostim (Leukine), filgrastim (Neupogen) and pegfilgrastim (Neulasta), and epoetinalfa (Epogen, Procrit) — may help stimulate the bone marrow to produce new blood cells. Growth factors are often used in combination with immune-suppressing drugs.
Having aplastic anemia weakens your immune system. You have fewer white blood cells in circulation to fight off germs. This leaves you susceptible to infections.
At the first sign of infection, such as a fever, see your doctor. You don’t want the infection to get worse, because it could prove life-threatening. If you have severe aplastic anemia, your doctor may give you antibiotics or antiviral medications to help prevent infections.
Aplastic anemia caused by radiation and chemotherapy treatments for cancer usually improves once you complete those treatments. The same is true for most other drugs that induce aplastic anemia.
Pregnant women with aplastic anemia are treated with blood transfusions. For many women, pregnancy-related aplastic anemia improves once the pregnancy ends. If that doesn’t happen, treatment is still necessary.