Blood Disorders-A

Anemia, Leukopenia, and Thrombocytopenia

Like any part of the body, the blood can also be afflicted with diseases and disorders that can compromise your health. Disorders of the blood range from mild, with no symptoms, to life-threatening medical emergencies.

The majority of the blood is plasma, which accounts for about half of the blood volume. Plasma is mostly water and contains dissolved salts and proteins, as well as hormones, electrolytes, fats, sugars, minerals, and vitamins. The other components of blood include:

Red blood cells—Red blood cells are responsible for carrying oxygen from the lungs to all other cells in the body, and for transporting carbon dioxide back to the lungs. Red blood cells are produced in the bone marrow. Each red blood cell has a life cycle of about 120 days, at which point they wear out and are destroyed in the spleen. Red blood cells are able to transport oxygen because of hemoglobin, an iron-containing molecule that binds to oxygen. About 90 percent of each red blood cell is hemoglobin, and each molecule of hemoglobin can carry four molecules of oxygen (Eastern Kentucky University 2005).

White blood cells—White blood cells are the backbone of the immune system. They fight infection by engulfing invading organisms or abnormal cells. There are five basic kinds of white blood cells: neutrophils, monocytes, lymphocytes, eosinophils, and basophils. Neutrophils are the most common form of white blood cell and are responsible for fighting infection.

Platelets—Platelets are responsible for blood clotting. They circulate constantly in the bloodstream. In the event of an injury, platelets gather (aggregate) at the injured site and touch off a chemical reaction that results in a blood clot. Abnormal platelet function may result in increased bleeding or the formation of dangerous blood clots where they don’t belong, which can cause a heart attack or stroke.
In this chapter, we will review three blood disorders—anemia (low red blood cells), leukopenia (low white blood cells), and thrombocytopenia (low platelets). We will address how these disorders are diagnosed and conventionally treated and how to support the health of your red blood cells, white blood cells, and platelets with nutrition.

What Is Anemia?
Anemia is a common blood disorder characterized by a decrease in the amount of red blood cells, or a decrease in the capacity of red blood cells to transport oxygen. This results in a lack of oxygen reaching the body’s cells and tissues. Referred to as the “hidden hunger” by the World Health Organization, anemia poses significant health risks worldwide. It affects between 2 percent and 15 percent of people in the United States (Abrahamian FM et al 2005). Women are about twice as likely to be anemic as men. This is especially true of premenopausal women; between 4 percent and 8 percent of premenopausal women have iron deficiency anemia (Abrahamian FM et al 2005; Conrad ME 2005).

Anemia is associated with poor health outcomes. In patients who have had a heart attack, anemia sharply increases mortality (Wu RC et al 2001), and it is a strong predictor of overall mortality in the elderly. Over a 5-year period, anemic people aged 70 to 79, 80 to 89, and 90 to 99 were 28 percent, 34 percent, and 48 percent, respectively, more likely to die than people of the same ages who were not anemic. Stroke is commonly associated with anemia (Kikuchi M et al 2001).

Anemia is associated with the following symptoms (Abrahamian FM et al 2005):

Weakness and fatigue
Irritability
Shortness of breath
Headaches
Sore tongue and bleeding gums
Pallor
Nausea and loss of appetite
Faintness and dizziness
Confusion and dementia
Increased heart rate
Heart failure (in severe cases)
Depending on its cause, anemia is generally classified in three ways: excessive bleeding, decreased red blood cell production, or increased red blood cell destruction.

Excessive bleeding
This form of anemia occurs when someone loses too much blood, either because of an injury (acute anemia) or a chronic disease. When the body loses a large amount of blood, the body reacts by pulling water from surrounding tissues into blood vessels to maintain a healthy blood pressure. This dilutes the blood, lowering the proportion of red blood cells.

Excessive bleeding can result in very serious anemia, depending on the nature of the injury. Acute anemia that involves the rapid loss of great volumes of blood can result in heart attack or stroke (Beers MH 2003). However, anemia related to chronic conditions, such as recurrent nosebleeds or ulcers in the stomach, develops more slowly and may not be as obvious. This type of anemia sometimes occurs as a result of cancer, especially colon cancer.

Chronic blood loss can cause a deficiency in iron. Iron deficiency anemia is the most common form of anemia (Leung AK et al 2001; Rasul I et al 2001), affecting about 2 billion people worldwide (Lynch SR 2005). It results in decreased red blood cell production.

Because it can take several months to deplete the body’s supply of iron, it might take a long time for symptoms to develop. Iron deficiency anemia caused by blood loss is one of the most common forms of anemia in the United States (Beers MH 2003). In women, this condition is frequently related to excessively heavy menstrual bleeding; in men, it is often related to gastrointestinal bleeding.

Decreased red blood cell production
Red blood cells are manufactured in the bone marrow. This process relies on various nutrients, including iron, vitamin B12, and folic acid, as well as smaller amounts of vitamin C, riboflavin, and copper. Also, the production of red blood cells is stimulated by a hormone called erythropoietin. Deficiencies in any of these nutrients or in erythropoietin can result in anemia. Besides iron deficiency anemia caused by bleeding, other forms of anemia include:

Pernicious anemia (vitamin B12 deficiency)—

It is estimated that 300,000 to 3 million people in the United States have a vitamin B12 (cobalamin) deficiency (Diamond AL et al 2004). Vitamin B12 deficiency is rarely related to a dietary deficiency. Rather, vitamin B12 relies on intrinsic factor, a protein generated by cells in the stomach, to be bound to vitamin B12 and then absorbed in the ileum, the last segment of the small intestine. People who lack intrinsic factor cannot use the available vitamin B12, meaning that anemia can develop even if large amounts of vitamin B12 are consumed. Besides a lack of intrinsic factor, pernicious anemia can be caused by Crohn's disease, stomach surgery, or a strict vegetarian diet. Breast-fed infants of vegan mothers are particularly at risk of vitamin B12 deficiency.
Folic acid deficiency anemia—Folic acid is abundant in green leafy vegetables. Because many people in industrialized countries don't eat enough vegetables, folic acid deficiency is more common than pernicious anemia. Folate deficiency is found in malnourished individuals (especially alcoholics), infants who are fed only cows’ milk, pregnant women, and adults over age 60. It can also be caused by diseases that affect absorption in the small intestine, including Crohn's disease.
Anemia of chronic disease—Anemia is associated with various chronic diseases and conditions, including infections, inflammatory diseases, and cancers that affect the ability of the body to produce red blood cells (Brill JR et al 2000; Bron D et al 2001). Diseases or conditions that are associated with anemia include cancer (Gillespie TW 2003; Knight K et al 2004), HIV/AIDS (Sullivan PS et al 1998), and testosterone deficiency (Bain J 2001; Zitzmann M et al 2000). In patients with cancer or HIV/AIDS, anemia is associated with increased mortality (Buskin SE et al 2004; Caro JJ et al 2001). Testosterone deficiency can cause anemia because the hormone helps stimulate kidneys and bone marrow to produce erythropoietin and stem cells. Symptoms of testosterone deficiency include decreased libido, impotence, infertility, fatigue, and decreased muscle mass and strength (Baker HWG 1995).
Additionally, aplastic anemia is a rare form of anemia that occurs when bone marrow fails to produce all three types of blood cells: red blood cells, white blood cells, and platelets. Causes of aplastic anemia include autoimmune diseases, viruses, or chemicals (e.g., benzene or pesticides). Symptoms include frequent infections (white blood cells are reduced), fatigue (red blood cells are reduced), and bleeding (platelets are reduced).

Increased red blood cell destruction
If the rate of red blood destruction is more rapid than the creation of new red blood cells, hemolytic anemia occurs. This form of anemia is less common than the other two. Hemolytic anemia can result from infection, certain drugs, autoimmune disorders in which the body attacks and destroys its own red blood cells, and inherited disorders such as sickle cell anemia or thalassemia.

Additionally, an enlarged spleen can result in anemia. The spleen is responsible for destroying old red blood cells; an enlarged spleen can increase the rate of red blood cell destruction beyond the body’s ability to manufacture new red blood cells.

Sickle cell anemia is the most common inherited blood disorder in the United States, affecting 1 in 500 African Americans and 1 in 2000 Hispanics of Caribbean or South or Central American descent (Pegelow C et al 2004). In this disease, the red blood cells are abnormally shaped (they resemble boomerangs), and their blood carrying capacity is reduced. These cells are fragile and break up as they travel through blood vessels, resulting in a reduced red blood cell count.

Thalassemia occurs when there is an imbalance in the production of one of the amino acid chains that makes up hemoglobin. Many people who have thalassemia also have mild anemia.

Autoimmune disorders can cause anemia if the body identifies red blood cells as invader pathogens and attacks them. In most people, the cause of autoimmune anemia is unknown (Beers MH 2003).

Diagnosing Anemia

Anemia is typically diagnosed with a complete blood count (CBC) test. Anemia is defined as a decreased number of red blood cells, a decrease in the quantity of hemoglobin, or a lowered hematocrit (the ratio of red blood cells to whole blood). The following Table shows the reference ranges for these measurements.

Reference Ranges for Blood Indicators*
Indicator-Men&Women

Red blood cell count:
Men-4.10-5.60 (×10­6/µL)
Women-3.80-5.10 (×10­6/µL)

Hemoglobin
Men-12.5-17.0 (g/dL)
Women-11.5-15.0 (g/dL)

Hematocrit
Men-36%-50%
Women-34%-44%

*µL=microliter; g/dL=grams per deciliter.


If initial blood tests analyzing hemoglobin, red blood cell count, or hematocrit indicate anemia, additional testing should be done to determine the cause of anemia (Brill JR et al 2000). Additional tests may include:

Stool tests—If a person has symptoms of anemia and has noticed bleeding, a physician may test for the presence of blood in the stool, which can indicate chronic bleeding that would cause anemia.
Iron deficiency tests—Iron deficiency is best diagnosed by blood testing (Uthman E 2005). Additionally, physicians may test for levels of transferrin (a protein that carries iron) or for ferritin (a protein that stores iron).
Other tests—Laboratory tests for vitamin B12 anemia are usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels (Baik HW et al 1999). Similarly, folic acid levels can be measured to detect a deficiency in folic acid.

Managing Anemia
Management of anemia depends on the cause. If anemia is caused by chronic bleeding, for example, the goal is to stop the bleeding; the anemia may then resolve on its own. For instance, in patients with HIV/AIDS, anemia can be treated by temporarily suspending treatment with the antiretroviral drugs used to attack the virus. In extreme cases of acute blood loss, a transfusion may be necessary to raise the red blood cell count.

In some cases, anemia is treated by prescribing erythropoietin, a hormone that stimulates red blood cell production. Erythropoietin is a very expensive drug that is sometimes used to treat severe anemia caused by chemotherapy, certain anti-HIV drugs, testosterone deficiency, or chronic kidney failure. Erythropoietin, taken along with iron, may help reduce the need for a red blood cell transfusion. It is particularly important to supplement erythropoietin with iron because erythropoietin causes the iron to be utilized to form new red blood cells. A poor result may occur if an iron supplement is not prescribed concurrently with erythropoietin.

If the anemia is caused by a genetic disorder (such as sickle cell anemia), blood transfusions may be used to raise the red blood cell count while other drugs are prescribed to treat the genetic disorder itself.

Nutritional Support
Some forms of anemia respond well to nutritional therapy, including anemia caused by iron deficiency or folic acid deficiency.

Iron
In the United States, dietary iron deficiency is rare because of a diet high in iron-rich foods such as red meat, beans, egg yolks, whole-grain products, nuts, seafood, iron-fortified cereals, dark green leafy vegetables, and dried fruit. However, some people in the United States have a higher need for iron, including children, pregnant or menstruating women, strict vegetarians, and long-distance runners.

Oral iron supplements are available to treat iron deficiency anemia. However, gastrointestinal malabsorption syndromes may require the intramuscular or intravenous injection of iron dextran (Imferon) by a physician. Iron protein succinate (sold as a drug in Germany) may be the most effective oral treatment of iron deficiency anemia. This form of iron has been evaluated in multicenter clinical trials to determine efficacy and tolerability (Kopcke W et al 1995). The following effects were seen in anemic adults after only 60 days:

23 percent increase in percentage of red blood cells (hematocrit)
30 percent increase in blood oxygen-carrying capacity (hemoglobin)
6 percent increase in total number of red blood cells
One new and novel approach to iron supplementation is the use of ferritin, a protein that is involved in the storage of iron and can be found naturally in foods like beans. Newer studies have shown that ferritin supplementation may be able to boost iron levels without the side effects associated with iron supplementation (Theil EC 2004). In one study, a ferritin complex was shown to be effective in children who had anemia that was caused by hemodialysis (Warady BA 2005).

Folic acid
The recommended daily requirement of folate is difficult to obtain from food sources alone. Symptoms of folic acid deficiency may include diarrhea and other gastrointestinal problems. Because supplementation with folic acid can mask a vitamin B12 deficiency, folic acid and vitamin B12 should be taken together.

Anemia caused by folic acid deficiency normally responds quickly to oral folic acid and vitamin B12 supplementation. Anticonvulsants, antituberculosis drugs, alcohol, and oral contraceptives have been associated with low serum levels of folate (Lambie DG et al 1985).

Vitamin B12
In pernicious anemia, the body lacks intrinsic factor, which is needed to carry vitamin B12 from the digestive tract into the bloodstream. This condition often affects the gastrointestinal tract and the nervous system, with symptoms that range from weakness to vertigo to angina. Vitamin B12 is available as a supplement in multiple forms, including cyanocobalamin and methylcobalamin. The conventional treatment for pernicious anemia is an intramuscular injection of cyanocobalamin, often followed by lifelong supplementation with vitamin B12.

One study, however, showed that subjects given 1500 micrograms (mcg) of methylcobalamin orally daily for 1 to 3 months experienced prompt correction of their anemia, with recovery of neurological disturbances observed after 1 month and recovery of hemoglobin and serum concentrations within 2 months. These results imply that orally administered methylcobalamin may be as effective as traditional vitamin B12 injections for treatment of pernicious anemia (Takasaki Y et al 2002). If, however, red blood cell levels fail to respond to treatment with methylcobalamin, conventional treatment should be sought.

Copper, zinc, and selenium
Trace minerals can be an adjunctive nutritional therapy to reduce the effect of anemia on normal red blood cell function. Copper, zinc, and selenium are used in biochemical processes such as cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals (Chan S et al 1998).

L-carnitine

Patients with anemia caused by end-stage renal disease respond to therapy with L-carnitine. In one study, L-carnitine therapy increased hematocrit and decreased resistance to erythropoietin (Horl WH 2002).

Testosterone therapy
Anemia associated with testosterone deficiency can be addressed with testosterone replacement therapy, which can stimulate erythropoietin production and increase hematocrit. Potential candidates for testosterone replacement therapy should undergo a complete physical examination including a complete medical history and a hormone profile (Morales A et al 2000).