Aplastic Anemia: The Disease of the Future

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Chelsey Fal                                                                                                                    Marlen Harrison

English 202, Section 016

31 March 2008

Aplastic Anemia:  The Disease of the Future

At the time, I was in fifth grade, around the age of 11.  I remember watching my mom run to the garage with the phone in her hand.  My father had just arrived home from getting his hair cut.  There was a doctor waiting to talk to my father about a recent blood test he had.  The doctor directed him to get to the nearest hospital as soon as possible; his blood counts were dangerously low.

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, a cancer causing agent, 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.  How could these occupational/environmental exposures to certain chemicals lead to the prevalence of aplastic anemia in the future?

Aplastic anemia is a non-contagious, rare blood disorder that hinders the production of blood cells in the bone marrow.

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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 severe aplastic anemia.  Severe aplastic anemia is classified by a bone marrow cellularity of less then 25 percent.

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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.  The American Cancer Society defines neutrophils as a type of white blood cell that helps to fight infection.  Wordnet 3.0 defines reticulocytes as immature red blood cells.  Very severe aplastic anemia is classified by a neutrophil count of less than 200 per micro liter.  Below is a table taken from an article written by Elaine Keohane (168):

Table 1. Classification of acquired aplastic anemia

Non-severe aplastic anemia (NSAA) or moderate

aplastic anemia (MAA)

Presence of” at least two of the following:

Hemoglobin < 10 g/dL

Platelets: 20-50 X lO’VL

Neutrophils 0.5-1.5 X 107L

Severe aplastic anemia (SAA)

Bone marrow cellularity <25%, or 25% to 50%

with <30% residual hematopoietic cells, and

presence of at least two of the following:

Neutrophils <0.5 X 107L

Platelets <20 X 107L

Reticulocytes <20 x lO’VL

Very severe aplastic anemia (VSAA)

Includes criteria of SAA plus:

Neutrophils <0.2 X 107L

166 VOL

Table 1 helps to simplify the blood counts in order to compare how moderate or severe the disease is.  Based upon the severity of the disease is how doctors approach the treatment.

My father was changing.  He was always tired and irritated.  He did not know what was wrong with him.  He had always been in shape and healthy.  We were unaware of the awful news that was about to be broken to us.  When my father was diagnosed with aplastic anemia, the doctors referred it to aplastic anemia as a “cancer of the blood.”

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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.  If the blood counts are lower than normal, this may be a sign of aplastic anemia.

The doctor then needs to examine a sample of the patient’s bone marrow to diagnose the disease.  This procedure can be done by a bone marrow aspiration or a 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.

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Fig. 1.  Randy Ramage.   Aplastic Anemia & Myelodysplasia (http://www.citylightsnews.com/randy/glossary/glossary_b.htm).

Figure 2.  Randy Ramage.   Aplastic Anemia & Myelodysplasia (http://www.citylightsnews.com/randy/glossary/glossary_b.htm).

Figure 1 is a picture of a person’s bone marrow without aplastic anemia.  Figure 2 is an individual’s bone marrow affected by aplastic anemia.  Notice the absence of blood cells in Figure 2 as compared to Figure 1.

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 employees, pesticide manufacturers, pipe fitters, printers, refinery workers, rubber

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workers, shoe/leather workers, synthetic rubber producers, tanker men, and truck drivers.

The Agency for Toxic Substances and Disease Registry defines arsenic as an organic compound released from the earth’s crust.  Arsenic can be measured by a urine test, which is the best way to find arsenic in the body.  Dictionary.com states that calcium arsenate is highly toxic and used in insecticides and germicides.  Below is a table taken from an article written by Elaine M. Keohane (166):

Table 2. Agents infrequently associated with acquired aplastic anemia

Occupational and environmental exposures

Benzene

Insecticides

Petrochemicals

Lubricating agents

An article written by Garry Crystal 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.  “In the United States, the maximum amount of benzene permissible in water is 0.005 milligrams per liter” (Crystal, 2003).  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.

It is very important to state that the incidence of aplastic anemia is higher in the Far East than that of the incidence in the West.  Research has not found a definite answer as to why this is, but it may be caused by a few different factors such as, socioeconomic status, rice farming, and pesticide use.

Large numbers of aplastic anemia cases have come from hospitals located in

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China, Korea, Thailand, and Asia (Issaragrisil, et. al., 1).  The prevalence was significantly high in the specific location of the Mudanjiang region of China, as well as in certain populations of people, such as, industrial workers in Japan (Issaragrisil, et. al., 1).  Aplastic anemia is diagnosed in about 500 people in United States every year (Young, 1); approximately two cases per million occur in North America and Europe (Keohane, 165).

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.

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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 physicians 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.  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.

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.

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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.

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).

I do not have access to aplastic anemia research centers where I can study or interview patients with this disease.  I do have knowledge of the disorder being influenced by excessive exposure to specific agents in the occupational environment itself.  How?  My father was employed at the Monessen City Garage in Pennsylvania.

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He was overly exposed to the chemical benzene without taking any precautions.  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 a few 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 that 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.

When I emailed my father’s hematologist I asked her three different questions.  The first question I asked her was, “When did you first encounter a patient with aplastic anemia?”  She responded that the first person she encountered with aplastic anemia was not a patient, but a friend that she went to high school with.  (Aplastic anemia starts to seem rather unrare to me after hearing that.)  Her friend ran on the track team.  Unfortunately, at that time, there was not any treatment and he passed away.  This encounter is what led her to become interested in medicine, which answered my question to her of how she reacted.

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She also responded that her first patient with aplastic anemia was diagnosed about 15 years ago.  She is a hematologist, which is defined as which is a doctor who studies the blood and blood-producing organs by Merriam-Webster Dictionary, such as the bone marrow.  Aplastic anemia was not difficult for her to diagnose at the time, since the bone marrow malfunctions in producing the blood.

My father was diagnosed with aplastic anemia about 10 years ago.  His doctors had a difficult time figuring out what was wrong with him.  They had performed stress tests, electrocardiograms, but never drew any blood.  The last test they performed on him was a blood test.  The results came back showing his blood count levels were extremely low and he was rushed to the nearest hospital.  They were unable to specifically prove that the exposure to benzene had caused aplastic anemia to develop because it hardly showed up in his blood results.  My father had continued to work at the City Garage while the disease continued to progress and as he was undergoing tests to figure out what was wrong.  His hematologist says it is safe to assume that if the detection of benzene in his system would have been sooner than what it was, he probably would have recovered.  My father described his job as rolling blacktop and spraying pesticides without any form of protection.  Unfortunately, it took his diagnosis to lead the City Garage in taking caution when using chemicals.

Could aplastic anemia develop into the disease of the future?  It is rather possible.  My father is an example of one of the two people per million in North America who was diagnosed with aplastic anemia.  There is not a direct link between environmental and occupational exposures to the specific agents discussed in this paper.

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There is a correlation between the specific agents and the risk of developing aplastic anemia due to excessive exposure though.  If proper precautions, such as wearing the correct clothes or some sort of apparatus to hinder breathing in these agents are not taken, the risk of aplastic anemia is significantly higher.  Perhaps further research needs to be conducted to determine the incidence ratios of the Eastern countries and the Western countries.

He was changing again.  He was sick for a few months and would not go to the doctor in fear that something would be going wrong.  At the beginning of March 2008, my mother rushed him to the emergency room.  A few days later, he was diagnosed with Acute Myelogenous Leukemia.  Not only can aplastic anemia be a deadly disease but it can lead to other diseases.  My father is putting up one hell of a fight.  After one week of chemotherapy, the doctors found that there are not any cancerous cells in his bone marrow or his bones.

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Works Cited

Arsenic.  Agency for Toxic Substances and Disease Registry.  Atlanta, GA: 5 Oct. 2007.

<http://www.atsdr.cdc.gov/tfacts2.html#bookmark02>.

Calcium Arsenate.  Dictionary.com. Lexico Publishing Group, LLC: 2008.

<http://dictionary.reference.com/browse/calcium%20arsenate?r=14>.

Carson-Dewitt, Rosalyn.  “Aplastic Anemia.”  HealthAtoZ.  8 Fed. 2008.

<http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?req

uestURI=/healthatoz/Atoz/ency/aplastic_anemia.jsp>.

Issarigrisil, Surapol, et. al.  “Aplastic Anemia in Rural Thailand.”  American Journal of

Public Health.  Sept. 1997: Volume 87, Issue 9.

Issarigrisil, Surapol, et. al.  “Regional Patterns in the Incidence of Aplastic Anemia in

Thailand.”  American Journal of Hematology.  3 March 1999: Volume 61.

Issarigrisil, Surapol, et. al.  “The epidemiology of aplastic anemia in Thailand.”  The

American Society of Hematology. 15 Feb. 2006: Volume 107.

Keohane, Elaine.  “Acquired Aplastic Anemia.”  American Society of Clinical

Laboratory Science.  Summer 2004: Volume 17.

Muir, K. R., et. al.  “The role of occupational and environmental exposures in the

aetiology of acquired sever aplastic anemia: a case control investigation.”  British

Journal of Hematology.  Dec. 2003: Volume 123.

Neutrophil.  American Cancer Society.  22 Jan. 2008.

<http://www.cancer.org/docroot/GRY/GRY_0.asp?dictionary=&pagKey=N>.

Ramage, Randy.  Aplastic Anemia & Myelodyplasia Glossary.  13 March 2008.

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< http://www.citylightsnews.com/randy/glossary/glossary_b.htm>.

Reticulocyte.  Wordnet 3.0.  Princeton University: 2006.                                                           <http://wordnet.princeton.edu/perl/webwn?s=reticulocyte>.

Young, Neal.  Aplastic Anemia: Basic Explanation.  AAMDS: 2007.

Young, Neal.  “Acquired Aplastic Anemia.”  Annals of Internal Medicine.  2002:

Volume 136.