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Neutropenia

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Related Terms
  • AIN, autoimmune disease, blood disease, blood disorder, chemotherapy, congenital, congenital neutropenia, cyclic, cyclic neutropenia, immune disorder, febrile neutropenia, granulocytes, hematological autoimmune disorder, hematological disorder, immune system disorder, Kostmann disease, Kostmann's syndrome, low neutrophils, neutropaenic, neutropaenia, neutropenic, neutrophil granulocytes, neutrophils, primary autoimmune neutropenia, primary immune neutropenia, SCN, secondary autoimmune neutropenia, severe congenital neutropenia, white blood cells.

Background
  • Neutropenia is defined as a low number of neutrophil granulocytes, a type of white blood cell, in the body. White blood cells serve as the body's primary defense mechanism against infection and disease. In a healthy body, neutrophils make up 50-60% of circulating white blood cells. Neutropenic patients have an absolute neutrophil count (ANC) that is lower than 1,500 cells per microliter of blood.
  • Therefore, patients with neutropenia are more susceptible to disease and infection. Severe cases of neutropenia may even become life threatening.
  • Mild neutropenia usually causes no symptoms. Severe neutropenia increases the risk of infection, especially in the lungs, kidneys, blood, and/or skin.
  • Neutropenia can be acute (lasting less than three months) or chronic (lasting longer than three months). The condition occurs when the bone marrow does not produce enough neutrophils or an increased number of neutrophils are destroyed in the body. For instance, neutropenia is a common side effect of chemotherapy.
  • About three out of every one million individuals are diagnosed with agranulocytosis, (the complete loss of neutrophils) every year, and about one out of every one million people is diagnosed with drug-induced neutropenia annually.
  • Individuals who experience infections during severe, prolonged episodes of neutropenia have an increased risk of fatality. Morbidity also correlates with the length of time elapsed before the first dose of antibiotics is administered for a neutropenic fever (which accompanies an infection). Serious medical complications, like infection, occur in about 21% of patients with cancer and neutropenic fever.
  • Morbidity usually involves infections during severe, prolonged episodes of neutropenia.
  • Infections associated with neutropenia are treated with antibiotics. Other symptoms of the disease may be treated with blood transfusions, recombinant G-CSF (granulocyte-colony stimulating factor), recombinant G-CSF (granulocytes colony-stimulating factor), corticosteroids, splenectomy (surgical removal of the spleen) or bone marrow transplant.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. CancerSymptoms.org. Prevention of Neutropenia. . Accessed April 16, 2009.
  2. National Institutes of Health (NIH). . Accessed April 16, 2009.
  3. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2009. Accessed April 16, 2009.
  4. Neutropenia Support Association. About Neutropenia. . Accessed April 16, 2009.
  5. Smith TJ, Khatcheressian J, Lyman GH et al. 2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-based Clinical Practice Guidelines. J Clin Oncol. 2006 Jul 1;24(19):3187-205. Epub 2006 May 8.

Causes
  • Decreased production in bone marrow: Neutrophil ganulocytes are primarily produced in the bone marrow. However, hereditary disorders (like congenital neutropenia or cyclic neutropenia), cancer, certain medications, radiation, Vitamin B12 deficiency or folate deficiency may result in a decreased production of these cells.
  • Increased destruction: If a significant number of neutrophil granulocytes are destroyed, it may also result in neutropenia. For instance, neutropenia is a common side effect of chemotherapy. Chemotherapy-induced neutropenia typically occurs three to seven days after chemotherapy drugs are administered and continues for several days before recovering to normal levels. Conditions like aplastic anemia may also result in neutropenia.
  • Marginalization and sequestration: Hemodialysis may lead to neutropenia.

Symptoms
  • Some neutropenic patients, especially those with acute neutropenia, may be asymptomatic or experience mild symptoms. The disease is usually discovered when a patient has developed severe infections or sepsis.
  • Common symptoms of neutropenia include: skin rash, mouth ulcers, abscesses, thrush, periodontal disease, lymphadenopathy, mucous membrane abnormalities, fever, frequent infections, diarrhea, burning sensation when urinating, unusual redness/pain/swelling around a wound, sore throat, shortness of breath and chills.

Diagnosis
  • Some patients may be asymptomatic or experience mild symptoms. A complete blood count (CBC) test is usually conducted to determine how many and what types of cells are in the blood. Neutropenic patients have an absolute neutrophil count (ANC) that is lower than 1,500 cells per microliter of blood.
  • In serious cases, a bone marrow biopsy may be performed. During the biopsy, the patient is given a local anesthetic, and a sample of bone marrow is removed with a needle. The sample is then analyzed in the laboratory to determine whether or not the bone marrow is producing a sufficient number of neutrophils.

Treatment
  • Treatment for neutropenia depends on the cause. Any infection should be diagnosed and treated. According to the 1997 guidelines of the Infectious Diseases Society of America, neutropenic fever should be treated with empiric broad-spectrum antibiotics immediately. Treatment generally lasts between five to seven days.
  • According to the U.S Centers for Disease Control and Prevention (CDC) guidelines, vancomycin should be administered if Staphylococcus aureus infections are suspected. Delays in starting treatment are associated with higher mortality. Treatment generally lasts between five to seven days.
  • In rare cases when the condition is life threatening, treatment may include blood transfusion, medicines to stimulate white blood cell production and intravenous immunoglobulin (antibodies donated from blood samples).
  • Neutropenia is a common side effect of chemotherapy in cancer patients. According to the 2006 recommendations from the American Society of Clinical Oncology, blood cell growth factors should be administered to prevent febrile neutropenia when the risk of febrile neutropenia is 20% or higher. Recombinant G-CSF (granulocyte-colony stimulating factor) or G-CSF (granulocytes colony-stimulating factor) has been used to stimulate white cell blood production. However, some patients have developed leukemia or myelodysplastic syndrome following treatment with G-CSF.
  • Corticosteroids or immunosuppressive therapies may be administered in cases of autoimmune neutropenia.
  • In some cases, white blood cells collect in the spleen, causing it to enlarge. Possible treatment may include splenectomy (surgical removal of the spleen).
  • In rare situations a bone marrow transplant may be necessary.

Integrative therapies
  • Note: Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of neutropenia. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures.
  • Good scientific evidence:
  • Ginseng: For more than 2,000 years, the roots of ginseng have been valued in Chinese medicine. Several studies suggest that ginseng may be an effective agent for immune system enhancement. Additional high quality research is needed before a conclusion be made.
  • Avoid with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.
  • Probiotics: Probiotics are beneficial bacteria that are sometimes called friendly germs. They help maintain a healthy intestine and help the body digest foods. They also help keep harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. Research suggests that probiotics, especially those in milk or food, may be an effective agent for immune system enhancement. However, commercially produced yogurt may not be as effective. More studies are needed, particularly with yogurt, to give recommendations.
  • Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.
  • Zinc: Zinc formulations have been used since ancient Egyptian times to enhance wound healing. Zinc appears to be an essential trace element for the immune system, but research on the effect of zinc supplementation on immune function is scant and mostly focuses on patients with specific diseases. Zinc gluconate appears to exert beneficial effects on immune cells, improving CD3 and CD4 counts and increasing CD4/CD8 ratios in children. There are relatively few studies that examine zinc levels and the effects of zinc supplementation on the health of the elderly population. Further research is needed before a recommendation can be made.
  • Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.
  • Unclear or conflicting scientific evidence:
  • Amaranth oil: Amaranth is grown in Asia and the Americas and harvested primarily for its grain, which is used as a food source for bread, pasta, and infant food. Limited evidence suggests that amaranth may stimulate the immune system when combined with a heart-healthy diet in patients with heart disease and high cholesterol. However, additional studies of amaranth alone are needed to determine if it is effective for immunomodulation.
  • Amaranth is generally considered safe. Avoid if allergic or sensitive to amaranth. Use cautiously with diabetes, low blood sugar, low blood pressure, immune system disorders, or kidney disorders. Use cautiously if pregnant or breastfeeding.
  • Arabinogalactan: Arabinogalactans belong to a group of carbohydrates called polysaccharides. When consumed in the diet, arabinogalactan comes from the wood of the larch tree (Larix species) and is approved for use as a dietary fiber by the U.S. Food and Drug Administration (FDA). Early research has suggested that arabinogalactan may cause immune stimulation; however, its effect on immunity in healthy volunteers is not clear. More evidence is needed.
  • Avoid if allergic or sensitive to arabinogalactan or larch. People who are exposed to arabinogalactan or larch dust may have irritation of the eyes, lungs, or skin. Use cautiously in people with diabetes, digestive problems, or immune system disorders, and in people who consume diets high in fiber or low in galactose. Arabinogalactan should not be used during pregnancy or breastfeeding.
  • Arginine (L-arginine): L-arginine helps maintain the body's fluid balance (urea, creatinine), and aids in wound healing, hair growth, sperm production (spermatogenesis), blood vessel relaxation (vasodilation), and fights infection. Preliminary study results suggest that arginine may cause immunomodulation. More studies are needed to confirm these results.
  • Avoid if allergic to arginine or with a history of stroke or liver or kidney disease. Avoid if pregnant or breastfeeding. Use cautiously if taking blood-thinning drugs (like warfarin or Coumadin®) or blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control sugar levels.
  • Astragalus: In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. Western herbalists began using astragalus in the 1800s as an ingredient in various tonics. Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High quality human research is necessary before a firm conclusion can be drawn.
  • Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation or fever, stroke, transplant, or autoimmune diseases. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with a risk of bleeding. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, or diuretics or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.
  • Beta-carotene: Beta-carotene is a member of the carotenoids, which are very colorful (red, orange, yellow), fat-soluble compounds. They are naturally found in many fruits, grains, oil, and vegetables, including green plants, carrots, sweet potatoes, squash, spinach, apricots, and green peppers. Preliminary research of beta-carotene for immune system enhancement shows mixed results. Further research is needed before a conclusion can be drawn.
  • Avoid if sensitive to beta-carotene, vitamin A or any other ingredients in beta-carotene products.
  • Black currant: The black currant shrub is native to Europe and parts of Asia and is particularly popular in Eastern Europe and Russia. There is currently a lack of information in humans on the effectiveness of black currant seed for immunomodulation.
  • Avoid if allergic or hypersensitive to black currant, its constituents, or plants in the Saxifragaceae family. Avoid with hemophilia or in those taking blood thinners, unless otherwise recommended by a qualified healthcare provider. Use cautiously with venous disorders or gastrointestinal disorders. Use cautiously if taking MAOIs (antidepressants) or vitamin C supplements. Avoid if pregnant or breastfeeding.
  • Bovine colostrum: Bovine colostrum is the pre-milk fluid produced from cow mammary glands during the first two to four days after birth. Bovine colostrum confers growth, nutrient, and immune factors to the offspring. Bovine colostrum contains immunoglobulins or antibodies that are released into the bloodstream in response to infections. These immunoglobulins may help improve immune function and may be effective in treating immune system deficiencies. More evidence is required before a firm conclusion can be made.
  • Avoid if allergic or hypersensitive to dairy products. Use bovine colostrum with caution. Toxic compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlordiphenyldichloroethylene (DDE) have been found in human colostrum and breast milk. Thus, it is possible that these agents may be found in bovine colostrum. Avoid with, or if at risk of developing, cancer. Use cautiously with immune system disorders, atherosclerosis (hardening of the arteries) or if taking medications, such as anti-diarrheal agents (e.g. immodium), insulin, or CNS agents (amphetamines, caffeine). Avoid if pregnant or breastfeeding.
  • Cat's claw: Cat's claw is widely used in the United States and Europe, and it is one of the top herbal remedies sold despite a lack of high-quality human evidence. Preliminary research of cat's claw for immune system enhancement shows mixed results. Further research is needed before a conclusion can be drawn.
  • Avoid if allergic to Cat's claw or Uncaria plants or plants in the Rubiaceae family such as gardenia, coffee, or quinine. Avoid with a history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, or lupus). Use cautiously with bleeding disorders or history of stroke, or if taking drugs that may increase the risk of bleeding. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Cat's claw may be contaminated with other Uncaria species. Reports exist of a potentially toxic, Texan grown plant, Acacia gregii being substituted for cat's claw. Avoid if pregnant, breastfeeding, or trying to become pregnant.
  • Copper: Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains, fruits, shellfish, avocado, beef, and animal organs, (e.g. liver and kidney). Copper is involved in the development of immune cells and immune function in the body. Severe copper deficiency appears to have adverse effects on immune function, although the exact mechanism is not clear.
  • Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia, occasionally observed in disease states, including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down syndrome, and controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than 6mg/L. Use cautiously with anemia, arthralgias, or myalgias. Use cautiously if taking oral contraceptives. Use cautiously if at risk for selenium deficiency. The U.S. Recommended Dietary Allowance (RDA) is 1,000 micrograms for pregnant women. The U.S. RDA is 1,300 micrograms for nursing women.
  • Echinacea: Echinacea is a perennial herb that has been used to treat a variety of medical conditions. Echinacea has been studied alone and in combination preparations for immune system stimulation. It remains unclear if there are clinically significant benefits. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness.
  • Avoid if allergic to echinacea, its constituents, or any members of the Asteraceae/Compositae family (ragweed, chrysanthemums, marigolds, daisies). Use cautiously in patients prone to atopic reactions and in those with hemochromatosis and diabetes. Some natural medicine experts discourage the use of echinacea by people with conditions affecting the immune system, such as HIV/AIDS, some types of cancer, multiple sclerosis, tuberculosis, and rheumatologic diseases (such as rheumatoid arthritis or lupus). Use parenteral preparations of echinacea(no longer approved for use in Germany) cautiously. Use tinctures cautiously with alcoholic patients or in patients taking disulfiram or metronidazole. Avoid using echinacea in patients presenting for anesthesia. Use cautiously if pregnant or breastfeeding.
  • Gamma linolenic acid (GLA):Gamma linolenic acid (GLA) is a dietary fatty acid that is found in many plant oil extracts. Few clinical trials have investigated the effect of GLA on immune responses in healthy human subjects. GLA, as blackcurrant seed oil, may offer some benefits. Further study is required to determine if GLA is beneficial for immune enhancement.
  • Use cautiously with drugs that increase the risk of bleeding like anticoagulants and anti-platelet drugs. Avoid if pregnant or breastfeeding.
  • Goldenseal: Goldenseal is one of the five top-selling herbal products in the United States. Goldenseal is sometimes suggested to be an immune system stimulant. However, there is little clinical evidence in this area. More research is needed before a firm conclusion can be drawn.
  • Avoid if allergic or hypersensitive to goldenseal or any of its constituents (like berberine and hydrastine). Use cautiously with bleeding disorders, diabetes, or low blood sugar levels. Avoid if pregnant or breastfeeding.
  • Maitake mushroom: Maitake mushrooms (Grifola frondosa) are fungi that can be eaten. Maitake has been used both as a food and for medical conditions. Beta-glucan extracts from maitake have been studied for immune stimulation. Additional high quality research is needed to make a conclusion.
  • Maitake has not been studied thoroughly in humans, and its effects are not well known. Because it has been used historically as a food, it is thought that low doses may be safe. Avoid if allergic or hypersensitive to maitake or its constituents. Use cautiously with low blood pressure, diabetes, or low blood sugar. Use cautiously if taking blood pressure medications, antidiabetic agents, immunostimulants, immunosuppressants, or interferons. Avoid if pregnant or breastfeeding.
  • Massage: The main goal of massage is to help the body heal itself. Touch is fundamental to massage therapy and is used by therapists to locate painful or tense areas, to determine how much pressure to apply, and to establish a therapeutic relationship with clients. Preliminary evidence suggests that massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.
  • Avoid with bleeding disorders, low platelet counts, or if taking blood-thinning medications (such as heparin or warfarin/Coumadin®). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously with a history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.
  • Meditation: Many forms of meditation have been practiced for thousands of years throughout the world, with many techniques originating in Eastern religious practices. Preliminary research reports increased antibody response after meditation. Further study is needed to better determine if meditation affects immune function.
  • Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professionals before starting meditation and should explore how meditation may or may not fit in with their current treatment plans. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.
  • Mistletoe: Once considered a sacred herb in Celtic tradition, mistletoe has been used for centuries for high blood pressure, epilepsy, exhaustion, anxiety, arthritis, vertigo (dizziness), and degenerative inflammation of the joints. A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further study is needed to determine if mistletoe is effective for immunomodulation.
  • Avoid if allergic or hypersensitive to mistletoe or to any of its constituents. Anaphylactic reactions (life threatening shock) have been described after injections of mistletoe. Avoid with acute, highly febrile, inflammatory disease, thyroid disorders, seizure disorders, or heart disease. Use cautiously with diabetes, glaucoma, or if taking cholinergics.
  • Qi gong: Qi gong is a type of traditional Chinese medicine (TCM) that is thought to be at least 4,000 years old. It is traditionally used for spiritual enlightenment, medical care, and self-defense. There is some evidence suggesting that internal Qi gong may help with treatment of immune deficiencies. However, the evidence is still unclear, and further research is needed to understand how Qi gong may potentially benefit immune function. Based on preliminary study, Chan-Chuang Qi gong therapy may be used to treat leukopenia (low white blood cell count) in breast cancer patients treated with chemotherapy. Further study is warranted.
  • Qi gong is generally considered to be safe in most people when learned from a qualified instructor. Use cautiously with psychiatric disorders.
  • Reflexology: Reflexology involves the application of manual pressure to specific points or areas of the feet called "reflex points" that are believed to correspond to other parts of the body. Some research suggests that self-administered reflexology may be beneficial for immune enhancement. Additional study is needed in this area.
  • Avoid with recent or healing foot fractures, unhealed wounds, or active gout flares affecting the foot. Use cautiously and seek prior medical consultation with osteoarthritis affecting the foot or ankle or with severe vascular disease of the legs or feet. Use cautiously with diabetes, heart disease, unstable blood pressure, cancer, active infections, past episodes of fainting (syncope), mental illness, gallstones, kidney stones, or with a pacemaker. Use cautiously if pregnant or breastfeeding. Reflexology should not delay diagnosis or treatment with more proven techniques or therapies.
  • Rose hip: Rose hips are the fruits that develop from the blossoms of the wild rose plant. It is unclear if rose hips affect immune function. More studies are needed in this area.
  • Avoid if allergic to rose hips, rose pollen, their constituents, or members of the Rosaceae family. Use cautiously if taking anticoagulant or anti-platelet aggregating agents, anticancer agents, anti-HIV medications, anti-inflammatory agents, antilipemics, aluminum-containing antacids, antibiotics, salicylates or salicylate-containing herbs, or laxatives. Use cautiously in patients who are avoiding immune system stimulants.
  • Shiitake: Lentinan, a constituent of shiitake, has been shown to modulate the immune system in some studies. However, there is currently a lack of reliable human evidence supporting the use of lentinan or shiitake for immunomodulation. Additional study is needed in this area.
  • Avoid if allergic or hypersensitive to shiitake mushrooms. Avoid if pregnant or breastfeeding.
  • Tai chi: Tai chi is a system of movements and positions believed to have developed in 12th Century China. Tai chi techniques aim to address the body and mind as an interconnected system and are traditionally believed to have mental and physical health benefits to improve posture, balance, flexibility, and strength. Tai chi may increase the body's immune response in older adults. For example, patients receiving varicella vaccines and who practiced tai chi showed increased immune responses. Although early study is promising, more study is needed to better determine if tai chi is effective for immune system stimulation.
  • Avoid with severe osteoporosis or joint problems, acute back pain, sprains, or fractures. Avoid during active infections, right after a meal, or when very tired. Some believe that visualization of energy flow below the waist during menstruation may increase menstrual bleeding. Straining downwards or holding low postures should be avoided during pregnancy, and by people with inguinal hernias. Some tai chi practitioners believe that practicing for too long or using too much intention may direct the flow of chi (qi) inappropriately, possibly resulting in physical or emotional illness. Tai chi should not be used as a substitute for more proven therapies for potentially serious conditions. Advancing too quickly while studying tai chi may increase the risk of injury.
  • Thymus extract: Thymus extracts for nutritional supplements are usually derived from young calves (bovine). Preliminary evidence suggests that thymus extract increases white blood cell counts. Additional study is needed to determine if thymus extract is effective for immune system stimulation.
  • Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to the potential for exposure to the virus that causes "mad cow disease." Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid with thymic tumors, myasthenia gravis (neuromuscular disorder), or untreated hypothyroidism. Avoid if taking hormonal therapy or immunosuppressants. Avoid if pregnant or breastfeeding; thymic extract increases human sperm motility and progression.
  • Vitamin A: Vitamin A is a fat-soluble vitamin. Vitamin A deficiency may compromise immunity, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.
  • Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity may occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.
  • Vitamin B6: Major sources of vitamin B6 include: cereal grains, legumes (beans), vegetables (like carrots, spinach, peas), potatoes, milk, cheese, eggs, fish, liver, meat, and flour. Vitamin B6 has been shown to be important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse immune system impairments in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a conclusion can be made.
  • Vitamin B6 is likely safe when used orally in doses not exceeding the recommended dietary allowance (RDA). Avoid if sensitive or allergic to any vitamin B6 product ingredients. Some individuals seem to be particularly sensitive to vitamin B6 and may have problems at lower doses. Avoid excessive dosing. Use cautiously if pregnant or breastfeeding.
  • Vitamin D: Vitamin D is found in many foods, including fish, eggs, fortified milk, and cod liver oil. The sun also helps the body produce vitamin D. Preliminary human evidence suggests that vitamin D and its analogues, such as alfacalcidol, may act as immunomodulatory agents. High quality clinical studies are needed to better understand the effects of vitamin D on immunomodulation.
  • Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; doses higher than recommended may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.
  • Vitamin E: Vitamin E exists in eight different forms ("isomers"): alpha, beta, gamma and delta tocopherol; and alpha, beta, gamma, and delta tocotrienol. Alpha-tocopherol is the most active form in humans. Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.
  • Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid doses greater than the recommended daily level in pregnant women and breastfeeding women.
  • Fair negative scientific evidence:
  • DHEA: DHEA (dehydroepiandrosterone) is a hormone that is produced by the adrenal glands. It is suggested by some textbooks and review articles that DHEA may be effective for immune system stimulation. However, current scientific evidence does not support this claim.
  • Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders or if taking anticoagulants or drugs, herbs, or supplements for diabetes, heart disease, seizure, or stroke. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Avoid if pregnant or breastfeeding.
  • Lycopene: Lycopene is a carotenoid found in human serum, and skin, liver, adrenal, lung, prostate, and colon tissue. It has been proposed that lycopene and other carotenoids, such as beta-carotene, may stimulate the immune system. However, several studies of lycopene supplements and tomato juice intake in humans do not report effectiveness for immune stimulation.
  • Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding.

Prevention
  • Neutropenia is a common side effect of chemotherapy in cancer patients. According to the 2006 recommendations from the American Society of Clinical Oncology, blood cell growth factors should be used to prevent febrile neutropenia when the risk of febrile neutropenia is 20% or higher. Recombinant G-CSF (granulocyte-colony stimulating factor) or G-CSF (granulocytes colony-stimulating factor) has been used to stimulate white cell blood production.

Types
  • Autoimmune neutropenia (AIN): Autoimmune neutropenia is most common among infants and young children. This form occurs when the body identifies the neutrophils as enemies and produces antibodies to destroy them. This type usually becomes less severe within about two years.
  • AIN is further classified as either primary or secondary. In primary AIN, neutropenia is the only abnormality. In secondary AIN, other pathologies occur, including systemic autoimmune disease, infections and malignancy. Secondary AIN is extremely rare in infants.
  • Congenital neutropenia: Congenital neutropenia (neutropenia at birth) is a rare form of the disease, which is usually discovered soon after birth. Individuals with this disease may experience premature loss of teeth and subsequent gum infections.
  • The most severe form of chronic congenital neutropenia, known as Kostmann's syndrome, is genetically heterogeneous. In most cases, an autosomal dominant mutation in the ELA2 gene causes the disease.
  • The gene responsible for many cases of the autosomal recessively inherited congenital neutropenia is HAX1. In this case, both parents have to be carriers of the recessive trait in order for the child to have congenital neutropenia. If both parents are carriers, there is a 25% chance that the child will have the disorder.
  • Some evidence suggests that mutations in neutrophils' elastase or in other genes linked to the syndromic forms of neutropenia disrupt its intracellular trafficking. The mutations may also initiate the unfolded protein response.
  • Other evidence suggests that there is an increase in apoptosis (cell death) of neutrophil precursors. However, these findings are controversial because some of the scientific data was falsified and retracted from publication.
  • Cyclic neutropenia: Cyclic neutropenia usually occurs every three weeks and lasts for about three to six days at a time. This form is frequently present among several members of the same family. In almost all cases, cyclic neutropenia is the result of autosomal dominantly inherited mutations in ELA2 gene, which encodes neutrophils' elastase.
  • Drug-induced: Many different types of drugs can cause neutropenia and agranulocytosis. Researchers estimate that about 75% of all cases of agranulocytosis in the United States are related to medication. Anti-neoplastic drugs suppress the bone marrow's production of neutrophils, which may lead to the disorder. Other drugs like clozapine, procainamide and anti-thyroid medications (like methimazole and sulfasalazine) can lead to the destruction of white blood cells. About 6-10% of drug-induced agranulocytosis cases are fatal.
  • Idiopathic neutropenia: Neutropenia is considered idiopathic when the disorder cannot be attributed to any other disease or condition. This form is rare, and it often causes life-threatening infections in both children and adults.

Classification
  • Mild neutropenia: When an individual's ANC is greater than 1,000, but lower than 1,500, the condition is considered mild. Individuals with mild neutropenia have a slight risk of developing infections.
  • Moderate neutropenia: When an individual's ANC is greater than 500, but less than 1,000, the condition is considered moderate. Individuals have a moderate risk of developing infections.
  • Severe neutropenia (Kostmann's syndrome): When an individual's ANC is less than 500, the condition is considered severe. Individuals with severe neutropenia have a serious risk of developing infections, especially in the lungs, kidneys, blood and skin because these organs are exposed to the most bacteria. If this condition is accompanied by a fever, it is known as febrile neutropenia. Severe cases of neutropenia may result in agranulocytosis, which is the complete loss of neutrophils.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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