Anemia is defined as a decrease in the ability of the blood to carry oxygen due to a decrease in the total number of red blood cells, each having a normal quantity of hemoglobin, or a diminished concentration of hemoglobin per red blood cell, or a combination of both. Clinically it is a term used in conditions associated with low hemoglobin.
Symptoms and signs of anemia
- Decreased work capacity
- Fatigue,
- Weakness
- Dizziness
- Palpitations
- Dyspnea on exertion
- Pounding head ache
The severity of the symptoms will depend on the degree of anemia, age of the patient, condition of the patient and other associated illness.
APLASTIC ANEMIA
Aplastic anemia is a rare disorder characterized by decreased production of blood cells. In aplastic anemia there is decrease or stoppage of production of these cells depending on the severity of the disease. Aplastic means “not exhibiting growth” and anemia means deficiency of hemoglobin in the blood, which can be caused by either too few red blood cells or too little hemoglobin in the cells.
Aplastic anaemia is defined as pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate and with no increase in reticulin.
Classification of Aplastic anemia
Doctors classify aplastic anemia into three categories: moderate, severe and very severe
- Moderate aplastic anemia is the classification for those who have significantly reduced blood counts but not as reduced as occurs in severe aplastic anemia.
- Severe aplastic anemia is defined by a bone marrow cellularity (a measurement of blood cell production) of less than 25% and at least two of the following: a neutrophil count less than half a billion per liter (<500/mm3), a platelet count less than 20 billion per liter (<20,000/mm3), a reticulocyte count less than 20 billion per liter (<20,000/mm3).
- Very severe aplastic anemia is defined by a neutrophil count of less than 0.2 billion per liter (<200/mm3).
The symptoms of aplastic anemia can include
1. Increased bleeding,
2. Bruising,
3. Petechiae (tiny, pinpoint-sized red or purple spots on the skin),
4. Susceptibility to infections,
5. Shortness of breath,
6. Fatigue,
7. Decreased alertness,
8. Dizziness
9. Lingering illness
Cause
In about 50 % of cases, aplastic anemia is 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. High doses of radiation and cytotoxic chemotherapy can produce aplastic anemia. Aplastic anemia can also follow exposure to some environmental toxins (such as benzene), certain medications, and certain viruses. Acquired aplastic anemia is not contagious nor it hereditary. Hereditary aplastic anemia is relatively rare, but does occur with diseases such as Fanconi’s anemia, Dyskeratosis Congenita, and Shwachman-Diamond syndrome.
- High-dose radiation and chemotherapy treatments. Although these cancer-fighting therapies kill cancer cells, they can also damage healthy cells, including stem cells in bone marrow. Secondary aplastic anemia can be a temporary side effect of these treatments.
- Exposure to toxic chemicals. Exposure to toxic chemicals, such as some used in pesticides and insecticides, may cause secondary aplastic anemia. Exposure to benzene — an ingredient in gasoline — also has been linked to secondary aplastic anemia. This type of anemia sometimes gets better on its own if you avoid repeated exposure to the chemicals that caused your initial illness.
- Use of certain drugs. Some medications, such as those used to treat rheumatoid arthritis and some antibiotics, can cause secondary aplastic anemia.
- Autoimmune disorders. An autoimmune disorder, such as lupus, in which your immune system begins attacking healthy cells, may involve stem cells in your bone marrow.
- A viral infection. Viral infections that affect bone marrow may play a role in the development of aplastic anemia in some people.
- Pregnancy. Aplastic anemia that occurs in pregnancy may be related to an autoimmune problem — your immune system begins attacking your bone marrow during pregnancy.
- Unknown factors. In about half of cases, doctors aren't able to identify the cause of aplastic anemia. This is called idiopathic aplastic anemia.
DIAGNOSIS
A diagnosis of aplastic anemia is based on the symptoms and history, blood tests, bone marrow biopsy and bone marrow aspiration.
CLINICAL PRESENTATION
The patients of aplastic anemia usually present with symptoms of anaemia, skin or mucosal haemorrhage or visual disturbance due to retinal haemorrhage. There is no lymphadenopathy or hepatosplenomegaly.
History
History of
drugs
being taken and the exposure to various insectisides
and
industrial chemicals plays an important role in the diagnosis of the
disease.
LABORATORY TESTS
The Complete Blood Count (CBC), is a group laboratory tests performed on a small amount of blood, usually taken from an arm vein. Together, these tests provide detailed information about the quantity and quality of each type of blood cell. It gives information about the different cells and its quantity in the blood
A complete blood count includes the following measurements
- Red blood cell (RBC) count
- Hemoglobin (Hb)
- Hematocrit/Pack cell volume (Hct/PCV)
- Mean corpuscular volume (MCV)
- Mean corpuscular hemoglobin (MCH)
- Mean corpuscular hemoglobin concentration (MCHC)
- Red cell distribution width (RDW)
- White blood cell (WBC) count.
- Differential leucocyte count(DLC)
- Platelet count.
CBC usually shows pancytopenia , although lymphocytes counts are preserved. The haemoglobin level, neutrophil and platelet counts are all uniformly depressed, but in the early stages isolated cytopenia, particularly thrombocytopenia, may occur. Examination of blood smear is is essential to exclude the presence of dysplastic neutrophils and abnormal platelets, blasts andother abnormal cells such as hairy cells. Anaemia is accompanied by reticulocytopenia, and macrocytosis
Bone marrow aspiration: Bone marrow aspiration is a technique in which a small amount of liquid bone marrow is extracted through a needle inserted into the back of the pelvis bone in the area of the hip. A bone marrow aspiration provides important information on the presence or absence of abnormal blood cells. However, because aspiration disturbs the marrow structure, the degree of bone marrow cellularity (the quantity and quality of the bone marrow cells) cannot be accurately determined.
Bone marrow biopsy : To get a more clear picture of marrow blood production, a bone marrow biopsy is done .This procedure involves the removal of a very small piece of bone marrow, this then studied. This provides the most reliable and specific information regarding bone marrow cellularity. Bone marrow aspiration and bone marrow biopsy are usually done at the same time so that the patient does not have to undergo multiple procedures
TREAMENT OF APLASTIC ANEMIA
Treatment
options for aplastic anemia depend on how severe the disease is. A
person with moderate aplastic anemia may not need any treatment.
Instead, doctors will check blood counts regularly to watch for signs
the disease is getting
worse.
Transfusions are not effective as a long-term treatment strategy for the following reasons:
- Frequent red cell transfusions can cause iron overload. Buildup of iron can damage key organs such as the heart and liver.
- Platelets last only a few days and the immune system eventually learn to recognize and destroy transfused platelets.
- White blood cells are rarely transfused to patients because they only last a few hours and can be associated with serious side effects including breathing difficulty and fever.
- White cell transfusions are usually reserved for cases of severe infections that have not responded to antibiotics.
Bone marrow transplant(BMT). A bone marrow transplant is considered as the best treatment for aplastic anemia. BMT is most successful in younger patients who have a donor whose bone marrow matches their own. The most successful treatment option for aplastic anemia is a bone marrow or peripheral blood stem cell transplant. Bone marrow transplants are most successful (restoration of blood counts equivalent to normal marrow function) in otherwise healthy children and teenagers or very young adults with matched marrow donors. To increase the likelihood of a successful transplant and to minimize potential complications, the patient needs a donor whose marrow tissue type matches his or her own as closely as possible. The patient and prospective donors are given a special blood test to identify proteins on the surface of their cells called human leukocyte-associated (HLA) antigens. This HLA type is then used to identify a matching donor. The most desirable donor is a perfectly HLA matched sibling, referred to as being HLA identical. The chance of a sibling being HLA identical is 25 percent per sibling (i.e. someone with two siblings has a 50 percent chance that one will be an HLA identical donor).
To prepare for a bone marrow transplant, the patient’s immune system and diseased marrow is destroyed, usually with some combination of chemotherapy and radiation so as to make room for the healthy marrow that will be transplanted and to prevent the patient’s immune system from rejecting the transplanted stem cells.
Liquid bone marrow is collected from the donor’s hip bones or blood stream stem cells is collected from the donor after administration granulocyte colony stimulating factor (G-CSF) This is the given to the patient following chemotherapy by an intravenous transfusion. These stem cells migrate to the bones of the patient and, in 2 to 4 weeks, begin making new, healthy blood cells. Blood counts are monitored continuously for signs of this engraftment and the patient are put on various medications to keep infections away while the new immune system is growing. In some patients the procedure has to repeated as the marrow fails to respond.
Sucess rates of BMT varies from 50% in urelated matched transplants to 80-90% in matched sibling transplant. The incidence of graft rejection is more in urelated matched transplant. This codition is termed as GVHD or graft versus host disease. This occurs on 5% of patients.
Antithymocyte globulin (ATG) or Antilymphocyte globulin (ALG) is a purified (horse or rabbit) serum that reacts against specific cells in the human immune system. Both work in the same way, reacting against specific cells in the human immune system. The cells it targets are called T-lymphocytes—the cells that are responsible for destroying or suppressing the stem cells in patients with aplastic anemia. ATG is typically given intravenously over four days for approximately four hours or longer a day. When used alone, ATG helps to restore blood production about 50 percent of the time. When used in conjunction with cyclosporine, the chances of the treatment working increase to about 65 percent.
Side effects of ATG
Side effects like fever, chills has been reported during the therapy. These effects usually disappear when the treatment is finished but can cause substantial discomfort if they occur.
A rare but severe side effect is anaphylaxis, a life-threatening allergic reaction in which blood pressure drops and breathing becomes difficult. Because of the risk of anaphylaxis, patients will usually be given a test doageskin test to determine if they are likely to develop allergies to ATG. Allergic patients can still receive ATG therapy, but will need to undergo a desensitization procedure in which small, gradually increasing doses of ATG are given to reduce the body’s reaction.
The two standard treatments, immunosuppressive therapy and transplant, have similar long-term survival rates for some groups of patients. Both treatments have potential risks and side effects .
The choice of the treatment depends on the age of the patient, his/her conditiions at that time like kidney function, liver function . Usually patient below 50 years of age are suggested BMT if a matched donor is avialable.Patients above 50 are usually recommended immunosuppresive therapy .
Precautionsto be taken
People with severe aplastic anemia are at risk for life-threatening infections. Even a common infection like a cold could become serious. To help prevent infection, people with severe aplastic anemia need to protect themselves from germs.Steps to take may include avoiding crowds and sick people
Gum bleeding while brushing is very common in patients in aplastic anemia as result of low platelet counts. A soft brush is always helpful in preventing this. I would recommend Colgate Ultrasensitive for this purpose( This is from personal experience, my dad has used many toothbrushes, but in the end found ultrasensitive to be the best. ).
Before going to bed at night, preferably wash you mouth with a antiseptic mouthwash which has low alcohol content (Chlorhexidine Mouthwash) .
Referrence
Guidelines for the diagnosis and management of aplastic anemia. British Journal of Haematology, 2003, 123, 782–801.