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Anemia-Thrombocytopenia-Leukopenia
Updated: 05/27/2003
Referred to as the hidden hunger by the World Health Organization, anemia poses a significant health risk worldwide. Approximately 3.5 million people in the United States have anemia. Additionally, 20% of all premenopausal women in the United States have anemia. The incidence of anemia is far greater in second- and third-world countries, where the death rate is still 100% for some forms of anemia. This protocol deals with three distinct blood diseases: anemia, thrombocytopenia, and leukopenia.
Anemia is generally defined as a decrease in the number of red blood cells or in the quantity of hemoglobin or lowered hematocrit. This reduced blood cell count reduces the amount of oxygen the blood can carry to the body.
Thrombocytopenia is a condition that occurs when the body does not have enough blood platelets or the platelets are damaged. A person can bleed uncontrollably from a large vessel or from small capillaries. Often this type of bleeding into tissue becomes visible as a bruise or red marks on the skin.
Leukopenia is an abnormal decrease in the number of white blood cells, often reducing immune system function.
ANEMIA
General Causes of Anemia
In a 1999 study, at Wright State University School of Medicine at Dayton, OH, researchers who were studying the management of common forms of anemia advised that
Anemia is a prevalent condition with a variety of underlying causes. Once the etiology has been established, many forms of anemia can be easily managed by the family physician. Iron deficiency, the most common form of anemia, may be treated orally or, rarely, parenterally. Vitamin B12 deficiency has traditionally been treated with intramuscular injections, although oral and intranasal preparations are also available. The treatment of folate deficiency is straightforward, relying on oral supplements. Folic acid supplementation is also recommended for women of child-bearing age to reduce their risk of neural tube defects (Little 1999).
Aging, viral infections, blood diseases, and a variety of drugs, as well as cancer chemotherapy and radiation therapy, can cause deficits in red blood cells, white blood cells, and blood platelet production (Baik et al. 1999).
Dietary anemia is caused by not consuming enough nutrients, losing needed nutrients, or the inability to absorb enough required nutrients. A hormone deficiency can sometimes cause anemia. Anemia is not a natural part of aging, but older people develop anemia more often than any other blood condition.
Symptoms of Anemia
- Weakness and faintness
- Shortness of breath
- Increased heart rate
- Headaches
- Sore tongue
- Nausea and loss of appetite
- Dizziness
- Bleeding gums
- Confusion and dementia
- Heart failure in some severe cases
Common Dietary Anemias
Vitamin B12 Deficiency (Pernicious Anemia)
Pernicious anemia occurs when the body does not have enough vitamin B12. Pernicious anemia usually means the person cannot absorb the vitamin, rather than an actual lack of the vitamin in the diet. Vitamin B12 deficiency is estimated to affect 10-15% of people over the age of 60. The laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels (Baik et al. 1999).
Vitamin B12 is used by our bodies to make red blood cells in the bone marrow. Interestingly, anemia is more common in the people of northern Europe.
The risks of getting pernicious anemia are increased by eating only a vegetarian diet, having stomach surgery (removing a part of the stomach, which makes intrinsic factors needed to absorb vitamin B12), thyroid disease, diabetes mellitus, or a family history of the disease.
If untreated, pernicious anemia can lead to serious health problems such as congestive heart failure; neurological problems; increased incidences of infections; and even impotence in males. Those with coronary artery or pulmonary disease are especially vulnerable to the oxygen deprivation that can be caused by anemia.
To treat pernicious anemia, physicians have typically given vitamin B12 injections. However, research shows that orally taken methylcobalamin may be as effective. In one study, 17 patients with pernicious anemia were evaluated: Seven subjects in the study group were given 1500 mcg of methylcobalamin daily for 7 days every 1-3 months. The seven subjects given the methylcobalamin showed prompt correction of hematological and neurological abnormalities, with recovery observed after 1 month for neurological disturbances and within 2 months for hemoglobin and serum concentrations. The study authors concluded that orally administered methylcobalamin may be as effective as traditional B12 injections for the long-term treatment of pernicious anemia (Takasaki et al. 2002).
Methylcobalamin has also shown effectiveness in protecting nerve tissue and brain cells. Based on its mechanism of action, it can be effective in slowing the progression of hard-to-treat neurological diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, and Parkinson's disease.
Folic Acid-Deficiency Anemia
Folate deficiency is generally found in malnourished individuals, especially alcoholics, infants fed solely on cow's milk, pregnant women, and adults over 60. Malabsorption syndromes often produce folate deficiency, and certain drugs (e.g., phenytoin, phenobarbital, primidone, isoniazid, and cycloserine) are associated with the attenuation of folate absorption and metabolism.
Oral supplementation with folic acid and vitamin B12 is a common treatment of folic acid deficiency. Folic acid deficiency responds quickly to supplementation.
Folic acid is metabolically inactive until it is converted into tetrahydrofolic acid (THF). Tetrahydrofolic acid is important to general health because it produces thymidylate, which acts as a courier of genetic messages to cell DNA. Additionally, folate has been shown to play a role in no fewer than six biochemical reactions, including the synthesis of methionine, synthesis of purines (thymine is a pyrimidine), and catabolism of histidine. The failure of folate to break down histidine results in accumulation of an intermediary metabolite, formiminoglutamic acid (FIGlu), which can be measured clinically and is a clinical marker for folate deficiency.
Because folic acid is needed for cell replication and growth, rapidly regenerating cells such as red blood cells and immune cells have a high need for it. Folic acid is found in many foods, especially asparagus, broccoli, endive, spinach, and lima beans.
Iron-Deficiency Anemia
When there is insufficient iron available for the normal production of hemoglobin, iron-deficiency anemia results. According to the World Health Organization, iron-deficiency anemia (IDA) has not been responsive to prevention and control efforts.
Subclinical consequences of micronutrient deficiencies such as hidden hunger, include compromised immune functions that increase the risk of morbidity and mortality, impaired cognitive development and growth, and reduced reproductive and work capacity and performance (Anon. 1998).
Iron-deficiency anemia, the most common type of anemia, strikes 20% of all premenopausal women in the United States. The primary cause is loss of blood resulting from menstruation. This type of anemia also commonly occurs during pregnancy.
The body's iron stores can be depleted either through insufficient intake or excessive loss. In the United States, dietary insufficiency of iron is a very rare condition, due to the combination of our meat-rich diet and iron fortification of food staples. One notable exception to this is the case of milk-fed infants and their mothers. Bovine milk has almost no iron. An iron-deficient state in babies may begin in the antenatal life of the mother who may be overtly or borderline iron-deficient (iron requirements are markedly increased in pregnancy due to the demands of developing fetal tissues). Fortunately, most infant formulas are now fortified with iron. Still, nutritional cases of IDA do occur. Individuals with gastrointestinal lesions (scarring) that cause poor absorption may also fail to assimilate sufficient iron.
As noted earlier, the most important cause of iron depletion is chronic blood loss. Aside from menstruation, other underlying causes of blood loss include chronically bleeding lesions of the gastrointestinal (GI) tract, reflux esophagitis, peptic ulcers, or gastric or colorectal adenocarcinomas.
Because these diseases may be undetected, all cases of iron-deficiency anemia should be thoroughly investigated for the presence of hidden bleeding sites. This is especially true in females who are not of reproductive age and in all males. Patients should insist on clinical testing to determine the source of any suspected bleeding.
Oral iron preparations are available for treatment of iron-deficiency anemia. Since acute iron overdoses are potentially fatal, iron tablets must be kept out of reach of children.
In certain cases, such as in GI malabsorption syndromes, it may be necessary to give parenteral iron. This preparation, iron dextran (Imferon7), may be given intramuscularly or intravenously. Since it may produce anaphylactic shock, iron dextran needs to be given under direct physician supervision. Transfusion, which immediately restores all iron stores, is very dangerous in chronically anemic patients because of the demand this new blood volume puts on an already taxed heart. Transfusion is rarely indicated for iron-deficiency anemia.
Since excess iron in the body can generate massive free-radical reactions, supplemental iron to correct an iron deficiency should be used sparingly. Some people mistakenly continue taking iron supplements long after a deficient state is corrected. The penalty for overloading the body with too much iron is a dramatically increased risk of cancer, heart disease, and neurological degeneration.
The Life Extension Foundation suggests that people with iron deficiency anemia (IDA) supplement with the minimum amount of iron needed to restore levels to the mid-normal range. Even high normal ranges of iron could increase the risk of degenerative disease. Iron protein succinylate (sold as a drug in Germany) may be the most effective oral treatment of IDA. This form of iron has been studied in 1800 patients in three multicenter clinical trials to determine efficacy and tolerability (Kopcke et al. 1995). These studies showed the following effects in anemic adults after only 60 days of iron protein succinylate supplementation:
- 23% increase in percentage of red blood cells (hematocrit)
- 30% increase in oxygen carrying capacity of blood (hemoglobin)
- 6% increase in total number of red blood cells
Some persons do not absorb iron properly because they take drugs that affect stomach acid secretion. Clinical studies show that absorption of iron protein succinylate is not inhibited by H2 receptor antagonist drugs or by food intake.
Iron deficiency is best diagnosed by checking serum ferritin to determine if the values are low. If serum ferritin is greater than 50 (mcg/L), IDA is essentially ruled out. However, if the serum ferritin level is less than 50 (mcg/L), a blood test called the soluble transferrin receptor (sTfR) assay should be obtained. This measures the receptors for transferrin. These receptors are the docking sites for iron. In the face of iron deficiency, the number of receptors is increased or upregulated. Therefore, if the sTfR is 28 or higher, the probability of IDA is very high. Regular blood tests to assess ferritin and, when indicated, sTfR will assist your physician in determining whether you need iron supplementation.
Other Nutritional Approaches
Anemia and associated diseases compromise the oxygen-transport capabilities of red blood cells and the normal immune function of both red and white blood cells due to increased adhesion, reduction, or malfunction. Scientific study strongly suggests that trace minerals may act as an adjunctive preventive therapy to reduce the effect of anemia on normal blood cell function.
Researchers at the Nichols Institute (San Juan Capistrano, California) reported the importance of trace minerals in a 1998 study:
"Copper, zinc, selenium, and molybdenum are involved in many biochemical processes supporting life. The most important of these processes are cellular respiration, cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals" (Chan et al. 1998).
The consumption of trace minerals such as 2 mg daily of copper, 30 mg daily of zinc, and 200 mcg daily of selenium as an adjunctive therapy for anemia and associated disease is recommended.
Antianemia Drugs
Epoetin alfa (sold under the names Procrit and Epogen) is a recombinant human erythropoietin that stimulates the division and differentiation of red blood cell progenitors in the bone marrow. Epoetin alfa is prescribed to treat severe anemia caused by defective red blood cell production usually due to cancer chemotherapy drugs, certain anti-HIV drugs, testosterone deficiency, and chronic kidney failure (erythropoietin is naturally produced in the kidneys). It should be noted that a clinically significant resolution to an anemic condition may require 2-6 weeks of epoetin alfa therapy, which must be intravenously administered. Therefore, it is not intended for patients who require immediate correction of a life-threatening anemic condition.
Acute anemia therapy usually requires blood transfusions. The goal of therapy in acute anemia is to restore the hemodynamics of the vascular system and replace lost red blood cells. To achieve this, mineral and vitamin supplements, blood transfusions, vasopressors, histamine antagonists, and glucocorticosteroids may be administered.
Preventing and Treating Anemia Caused by HIV Antiviral Drugs
Infection by the human immunodeficiency virus (HIV) is commonly associated with hematologic abnormalities (anemia, leukopenia, and thrombocytopenia). A 1998 study by the National Center for HIV stated that "the 1-year incidence of anemia was 36.9% for persons with acquired immunodeficiency syndrome (AIDS)" (Sullivan et al. 1998). Several causes have been identified, including direct HIV injury to bone marrow, anti-HIV drugs such as AZT, opportunistic infections in bone marrow, vitamin B12 and folate deficiency, radiation therapy, and hemo-phagocytic syndrome. HIV patients have an increased risk of infection because the neutrophils play an important role in the defense against bacterial and certain fungal infections.
Treatment strategies may include reducing or temporarily eliminating anti-HIV drugs and other conventional therapies that suppress bone marrow production of blood cells. Supplementation with 2000 mcg of vitamin B12 (sublingual or oral tablets) and 1600 mcg of folic acid is suggested because deficiencies of these vitamins can cause numerous AIDS-related complications. Epogen or Procrit should also be considered if oxygen-carrying capacity is low.
When Anemia Is Life-Threatening
Anemia can be a life-threatening disorder that is quite simple to treat. Unfortunately, many physicians often fail to test and properly diagnose the condition, resulting in 24-40% of hospitalized patients over age 65 being anemic. Compared to nonanemic people, blood-deficient individuals have high mortality rates from diseases such as heart failure, stroke, and cancer.
When the oxygen-carrying capacity of the blood is impaired (i.e., anemia), people with reduced blood flow to any organ (e.g., those with coronary artery disease) are at a much greater risk for infirmity and death. Cancer cells thrive in a low oxygen environment and even borderline anemia predicts higher mortality.
Anemia can be detected by a standard CBC blood test, yet practitioners often accept anemia as being a normal state in aged people and fail to treat it. Drugs used to treat severe anemia (e.g., Procrit, Epogen) are very expensive. Many insurance companies will not pay for these drugs unless the person's blood oxygen-carrying capacity is far below the standard reference range. This may mean that those most in need of antianemia drugs (such as cancer and congestive heart failure patients) are being denied access.
Anemia Can Predict Who Will Die from an Acute Heart Attack
In a 2001 New England Journal of Medicine study, physicians looked at blood counts of hospitalized heart attack victims. Anemia was a strong predictor of who was most likely to die.
One of the tests used in this study was hematocrit. Hematocrit measures the percentage of whole blood that is made up of red blood cells. Normal hematocrit ranges are between 36-50%. Hematocrit below 36% indicates anemia.
Heart Attack Patients'
Hematocrit Percentage |
Odds of These Patients
Dying within 30 Days |
| 5.0-24.0% |
78% |
| 24.1-27.0% |
52% |
| 27.1-30.0% |
40% |
| 30.1-33.0% |
31% |
| Over 33.1% |
(No increased risk) |
These statistics show that anemia sharply increases the risk that a heart attack victim will die within 30 days. The physicians also found a high prevalence of anemia among these elderly heart attack patients (Wu et. al. 2001). |