Aplastic Anemia: The Disease of the Future

Coping with a rare disease such as aplastic anemia is not an easy task. The hardest part to deal with is finding out what causes the disorder. I have not been diagnosed with the disorder, but my father has. The doctors believed the cause of his diagnosis was due to the exposure of benzene within his occupational environment. My father worked for the City Garage in Monessen, Pennsylvania.  He has told me stories of rolling blacktop and spraying pesticides without proper protection from the exposure to the chemicals in these certain agents.  I find that there is significant importance to knowing about the risks of developing aplastic anemia through occupational/environmental exposure.  “In the United States, the maximum amount of benzene permissible in water is 0.005 milligrams per liter (Crystal, 2003).”  How could these occupational/environmental exposures to certain chemicals lead to the prevalence of aplastic anemia in the future?

The Disease

            Aplastic anemia is a non-contagious, rare blood disorder that hinders the production of blood cells in the bone marrow.  Aplastic anemia is considered a bone marrow failure disease.  Bone marrow is located in the center of the bone and produces three types of blood cells. Red blood cells transport oxygen throughout the body. White blood cells help to fight infections. Platelets are involved in the process of clotting the blood.  This means the person is often fatigued, very susceptible to infection, and can possibly bleed to death due to injuries.  Bone marrow stem cells transform into red cells, white cells, and platelets (Young, 1). Doctor Neal Young states, “In aplastic anemia, there are not enough stem cells in the bone marrow to produce a sufficient quantity of blood cells (2).”  Aplastic anemia is an autoimmune disorder, meaning that the individual’s immune system attacks its own cells (Young, 2).

There are two types of aplastic anemia, acquired and hereditary.  The discussion of hereditary aplastic anemia is not important for this research.  Acquired aplastic anemia means that the disease developed due to an exposure to something, but in most cases, the cause is unknown.  Aplastic anemia can be classified as moderate, severe, and very severe.  These three criteria developed by Dr. Bruce Camitta are still used by most doctors (Young, 2).  Moderate aplastic anemia is classified by low blood counts.  One or more cell type counts may decrease.  Doctors may not prescribe treatment, but will monitor blood counts.  Moderate aplastic anemia may not be discovered until it develops into sever aplastic anemia.  Severe aplastic anemia is classified by a bone marrow cellularity of less then 25 percent.  It is also classified by a neutrophil count less than 500 cells per micro liter, a platelet count less than 20,000 per micro liter, or a reticulocyte count less than 20,000 per micro liter.  Very severe aplastic anemia is classified by a neutrophil count of less than 200 per micro liter.

Dr.  Young describes the symptoms of aplastic anemia as increased bleeding, bruising, susceptibility to infections, and shortness of breath, fatigue, decreased alertness, shortened attention span, pale skin, dizziness, and lingering illness (3).  To diagnose this disease, doctors will first review the patient’s symptoms and history, including possible exposure to toxins and other risk factors.  The doctor then needs to obtain a complete blood count by drawing blood from the patient.  A complete blood count is a test that “gives a profile of all the components of the blood (Young, 3).” This test allows doctors to compare the counts of the patient to the counts of accepting standards.  (Insert chart)  If the counts are lower than normal, this may be a sign of aplastic anemia.  The doctor then need to examine a sample of the patient’s bone marrow to diagnose the disease.  The procedure is called a bone marrow aspiration and bone marrow biopsy.  Dr. Young describes how the procedure is performed; a needle is inserted into the back of the pelvis bone near the hip (4).  During a bone marrow aspiration, a small amount of bone marrow is sucked into a syringe through the needle.  This procedure provides information on the presence or absence of abnormal cells.  During a bone marrow biopsy, a small piece of bone marrow is pulled out with the needle.  This procedure is the most reliable in regards to information on the bone marrow cellularity.  In aplastic anemia, the bone marrow cellularity is usually reduced.

Incidence

            Aplastic anemia is diagnosed in about 500 people in the United States every year; approximately two cases per million people per year (Young, 1-2). Although it is a rare disease, it can target anyone of any age, race, or gender (Young, 2). The unusual aspect of this disease is that the cause of it is commonly unknown, approximately 60 to 75 percent (Young, 2) of the cases (Carson-Dewitt). There have been certain factors that are linked to developing aplastic anemia. These factors include exposure to radiation, certain drugs, or chemicals. High doses of radiation and cytotoxic chemotherapy can produce aplastic anemia (Young, 2). Cytotoxic is defined as something that is a threat at destroying certain cells (Young, 19).

                                       Causes

            Rod De Llano’s aplastic anemia information site discusses some of the risk factors of developing aplastic anemia.  Excessive exposure to these agents may lead to the development of aplastic anemia arsenic and compounds, benzene, calcium arsenate, glycol ethers, heptachlor, lindane, 2-methoxyethanol, plutonium, radium, and 2, 4, 6-Trinitrotoluene.  High risk jobs include adhesive production, barge workers, chemical workers, dock workers, gasoline distribution workers, industrial plant workers who use solvents, newspaper press workers, offshore workers, painters, paper and pulp, pesticide manufacturing, pipe fitters, printers, refinery workers, rubber workers, shoe/leather workers, synthetic rubber production, tanker men, and truck drivers.

An article written by Garry Crystal, 2003-2008, discusses benzene.  Benzene has been linked to the development of aplastic anemia.  Benzene is an organic chemical compound with a sweet smell.  It is a colorless, flammable liquid.  Benzene is used in the production of plastic, oil, synthetic rubber, and in many dyes.  It is a carcinogen, a cancer causing agent, in cigarettes.  Benzene is also used in the manufacturing of drugs, detergents and pesticides.  To test if an individual has been exposed to benzene, a blood test needs to be taken.  The test must be performed shortly after exposure, because the chemical does not stay in the body’s system for very long.

Methods

            This research paper will discuss the likelihood of the prevalence of this disease in the future based upon the observations of research on occupational/environmental exposure to certain agents.  I will email my father’s hematologist and ask her of her opinion on the current prevalence of aplastic anemia.  I will ask her the following questions.

1.  When did you first encounter a patient with aplastic anemia?

2.  How did you react?

3.  Was it difficult to diagnose?

To demonstrate how rare the disorder is, research will be done by comparing the population of those with this disorder located in the Western region as to those in the Eastern region of the world. Aplastic anemia is two to three times more common in Asian countries (Young, 2). By researching the certain chemicals linked to aplastic anemia and what environments they can be found, I will help to prove 6that the increasing use of these chemicals could lead to the occurrence of aplastic anemia in the future.  I will discuss with my father how it felt to be diagnosed with such a rare disease.

Aplastic anemia in rural Thailand:  Its association with grain farming and agricultural pesticide exposure.

            The incidence of aplastic anemia is high in Thailand, “where many drugs can be purchased without prescription and pesticides are widely used (Issaragrisil).  A similar case-control study conducted by the International Agranulocytosis and Aplastic Anemia Study in Thailand is replicated.

Issaragrisil and his team report a new association with grain farming and a separate association with pesticide use that does not explain the finding for grain farming.  Since January 1989, the study has been in progress in Bangkok, where the population is 8.75 million (Issaragrisil, et. al).  In November 1991, the study was expanded to the province of Khonkaen, where the population is 7.64 million, and to Songkla, population is 4.99 million.  The aim of the study is to include all cases occurring in those regions.  The case patients admitted to the hospitals in these areas were chose by regular contact with hematologists or other physicians.

The case patients had to meet at least two of the following criteria: a white blood cell count of 3.5 X 109/L or lower, a platelet count of 50 X 109/L or lower, and a hemoglobin level of 100 g/L or lower or hematocrit level of 30 percent or lower.  A further criterion was a reticulocyte count of 30 X 109/L or lower.  The case patients had to be diagnosed by a bone marrow biopsy.  Patients given chemotherapy or radiotherapy were not included in the study.  The control patients, four or more, were selected for each case patient.  The control patients were selected of the same sex and around the same age as the case patients.

The subjects were given a standard structured interview by physcians or nurses that solicited demographic data, relevant medical history, and details of drug and pesticide use and exposure to radiation and chemicals.  There were 284 case patients and 1174 control patients from Bangkok, Khonkaen, and Songkla.  The ages ranged from under 25 to 60 or older.  Farmers were categorized in two different groups, grain farmers and those who farmed other crops.     Agricultural pesticide exposure that occurred one to six months before hospital admission was studied.

The assumption was that the grain farmers who used pesticides would have a higher risk and incidence.  The annual risk estimation was six cases per million grain farmers.  Other farming types, such as fruit or vegetables, the risk was less common.  There fore, grain farmers are at a higher risk of developing aplastic anemia.  But the prevalence of aplastic anemia was not linked to the exposure of pesticides.  Issaragrisil suggests that the correlation between aplastic anemia and grain farming may explain the prevalence of aplastic anemia in Thailand.  Research should be conducted on the specific exposures among grain farmers; agents in the water and soil, insect vectors, poor sanitation, flooded fields.

The role of occupational and environmental exposures in the etiology of acquired sever aplastic anemia: a case control investigation. 

            An interview-based case-control study in Great Britain was conducted by the United Kingdom Aplastic Anemia Study.  Consultant hematologists recruited cases that were diagnosed between July 1, 1993 and October 20, 1997.

Research based on the hypothesis of aplastic anemia being caused by occupational/environmental factors attempts to explain the correlation between occupations that involve being exposed to chemicals that can cause aplastic anemia. The United Kingdom Aplastic Anemia study was interview based and was a case control study of those diagnosed with aplastic anemia located in Great Britain. The study concluded that there was an increase in the risk of those associated with occupational exposure. Two hundred patients out of 309 cases that were eligible ended up being interviewed. The study concluded a high risk to those exposed to radiation and pesticides in the workplace.