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About Iron
Our need for iron:
Iron is so important that without it all life would cease to exist. Every living thing: plants, animals, human beings, bacteria (good and bad) and yes, even cancer cells all need iron to survive and grow.
Plants require iron to make chlorophyll. Plants, animals, and human beings require iron to make DNA, which encodes all life. Animals and humans also need iron to make hemoglobin, which delivers oxygen to the body; also, we need iron to make myoglobin in muscles.
Myoglobin is a protein like hemoglobin, except that it is an oxygen storage protein contained in muscles of the body. We call upon the oxygen stored in myoglobin when we use our muscles to walk, run, climb or move in any way.
It is critical that we have enough iron available at certain developmental stages of life. Children who develop anemia because they do not get enough iron during these important stages can have lower IQ's, problems with concentration and their body may not develop like others their age.
On the other hand, iron can be so deadly that 250 milligrams can poison a small child. Then, there are people who have genetic conditions that cause them to absorb too much iron. They can develop iron overload disease and become very ill.
What is iron?
Iron is mineral that can be found in plants, animals, soil, air, water, meteorites, and rocks, including ones found on the surface of the moon. Here on earth, plants absorb iron through their root systems; animals eat these plants. Humans consume these plants and animals. Many think iron is a heavy metal, which it is not. Iron is an essential micronutrient. Essential used in this way means that the body does not produce the nutrient; micronutrient means that the body only requires tiny amounts to function. The chart shows the atomic weights of metals.
Insert image; atomic weights
Once the iron is consumed, for people with normal iron metabolism, elaborate systems are in place to make certain that we get just enough of the metal. In some people with abnormal iron metabolism, too much iron can be absorbed. When this happens, iron collects in vital organs such as the liver, heart, joints, pancreas and pituitary causing these organs to function poorly or fail.
There are also people who cannot absorb iron very well, lose a lot of blood (accidents, menstruation, surgery) or cannot make red blood cells normally. These people can become anemic.
Types of iron we consume:
Humans can get iron from shots (injection) or IV (intravenous). They can also get iron from blood transfusions or by consuming (eating) iron that is in their food, or iron pills.
People consume two types of iron: non-heme and heme
Non-hem
e iron comes primarily from plants and heme iron comes primarily from meat. Plants do contain tiny traces of heme iron but not enough to make a difference. Meat contains both types of iron. About 55-60% of the iron in meat is non-heme the rest is heme iron.
Nonheme iron represents the majority of iron humans consume in their diets and is the type of iron in most supplements. Non-heme type of iron is inorganic and is found in grains such as rice, wheat, and oats. Non-heme iron is also found in nuts, fruits, vegetables, most iron pills, fortificants, or contaminant iron such as from water, soil or cooking utensils. Unlike heme iron, the iron from all of these sources must be changed before it can be absorbed.
Meat, especially red meat is the best source of heme iron. When we eat meat we consume the blood proteins, the hemoglobin and myoglobin contained in the flesh of the animal. Heme iron is easily absorbed by the body and the best source of iron for people who are iron deficient. Too much heme iron in the diet can increase the risk of disease for some people with abnormal iron metabolism such as hemochromatosis.
For persons with normal iron metabolism only 20 to 25 percent of the heme iron consumed is actually absorbed. For example, a four-ounce hamburger contains about 3 milligrams of iron; about 1.2 milligrams are heme and about 1.8 milligrams are non-heme. The amount of heme iron absorbed from that 4 oz hamburger would be approximately a third of a milligram. Persons with abnormal iron metabolism, such as hereditary hemochromatosis can absorb up to four times the iron as that of a person with normal metabolism. Therefore 80-100% of heme iron can be absorbed or approximately 1.2 milligrams from the same 4oz hamburger!
Many substances can reduce the amount of non-heme iron we absorb; these substances include tannins in coffee or tea, dairy, phytates (fiber), eggs and some types of chocolate. Calcium can impair the absorption of both non-heme and heme iron. Therefore if a person needs more iron, he or she should avoid these items to improve the amount of iron absorbed. But if a person has a problem of too much iron, he or she should use these items to help lower the amount of iron absorbed.
About iron image 001: inhibit or improve
Absorption, transport and storage of iron
Iron is primarily absorbed in a portion of the small intestine called the duodenum. Before iron can be absorbed however, it is exposed to stomach acid and changed into a form that is soluble.
About iron image 002 villi
Once iron is absorbed it is carried (transported) by a protein called transferrin. Transferrin is the major transporter of iron and ideally should be about 25-35% saturated with iron.
Transferrin molecules that are heavily loaded (saturated) lose the ability to hold onto (bind) iron. Unbound or free iron is highly destructive and dangerous. Unbound iron can trigger free radical activity, which can cause cell death, and destroy DNA.
Free iron can also provide nourishment for bacteria such as Yersinia, Listeria and Vibrio. These bacteria are harmless for people with normal iron levels, but when transferrin is highly saturated with iron Yersinia, , Listeria, and Vibrio, contained in raw shellfish such as oysters, can lead to septicemia (definition will include symptoms). Death by septicemia can occur within hours if a person has very high body iron levels. People with high iron should always take care not to eat raw shellfish or walk barefoot on a beach where they might step on an infected shells.
Some microorganisms are skilled in other ways in obtaining iron from human hosts. Staph, for example can break open red blood cells and extract the iron it needs. Another pathogen, the protozoan that causes malaria, can get into the red blood cell to obtain iron necessary to thrive. And finally, there are bacteria such as the one that causes tuberculosis, that grow best inside macrophages that are iron loaded.
Macrophages are white blood cells that protect us against disease; they scavenge for harmful invaders that enter our bloodstream. When the macrophage is called into action, it engulfs the bacteria or harmful debris and traps it so that it cannot thrive and spread disease in the human host. Iron-loaded macrophages are helpless to defend us against opportunistic infection and disease. Overwhelmed with an iron these macrophages can migrate to other parts of the body and release free iron to that organ. An example is iron-loaded alveolar (lung macrophages) that migrate to the bladder and increase the risk of bladder disease. For this reason, people who smoke are at risk for many diseases, especially cancer. Cancer cells thrive on iron.
About iron image 003 macrophage:
When working normally, transferrin binds to iron, and transports it to all tissues, vital organs, and bone marrow, so that normal metabolism, DNA synthesis, and red blood cell production can take place. Recently scientists have discovered that transferrin does not work completely alone in the transport of iron. Ceruloplasmin, a protein that binds with copper is involved in iron transport. Iron needs adequate amounts of copper to reach
some of its intended destinations, such as the brain.
Besides transferrin, two newly discovered proteins: divalent metal transporter 1 (DMT1) and ferroportin (FPN) are important to the transport of non-heme iron. DMT1 carries iron into the cell, while ferroportin carries iron out of the cell and into the bloodstream.
Iron that is contained (stored):
Ferritin is a protein that acts like a large holding vessel. Ferritin contains iron that we don't presently need. It is sometimes called an iron storage protein. Ferritin is produced by nearly every cell of the body. The brain contains huge amounts of ferritin, so does the liver. Ferritin is a very large molecule; one ferritin molecule alone can hold up to 4, 500 atoms of iron.
Elevated serum ferritin can be a sign that the person has inflammation due to disease, or that potential disease causing factors such as iron overload may be present.
Like transferrin, ferritin can also become unstable, and ineffective. Think of ferritin like a big sink; when this sink gets full, ferritin and its iron can be changed into something called hemosiderin.
Hemosiderin is a yellowish-brown substance that contains ferric oxide (rust). A small amount of hemosiderin in tissues is probably normal and may not be harmful, but when large amounts of the substance is allowed to collect in organs, it then becomes a threat to good health. Hemosiderin can accumulate in cells of the heart, liver, lungs, pancreas, central nervous system, thyroid, reproductive organs, skin, adrenals, pituitary and thyroid gland. When the build up of hemosiderin is great, the organ cannot function properly. For example, when beta cells (insulin producing cells of the pancreas) are loaded with hemosiderin, these cells become unable to produce or store adequate amounts of the hormone insulin, which results in diabetes.
Clearly, inadequate amounts or excessive accumulation of iron can endanger health, but iron can also be harmful to a person's health in yet another way.
How iron triggers free radical activity
Free radical activity, also called oxidative stress
As a chemical component of heme in hemoglobin iron is capable of carrying oxygen through out the body. Behaving in this way, iron is a lifesaver. However, "free" or unbound iron can contribute to free radical development.
Free radicals (FR) are normal byproducts of human metabolism as oxygen is utilized. FRs are atoms or a group of atoms that have at least one unpaired electron. More stable and less reactive chemical structures as a rule have their electrons all paired to one another. Since this is not the case with free radicals, FRs are constantly on the hunt for that additional electron and are highly reactive with other chemicals in the body.
Programmed from its creation to find its missing part, the FR steals electrons from anywhere in the body to make up for its missing partner. The free radical can steal from any cell in any organ, which includes the heart, pancreas, brain, liver, joints, etc. Free radicals can also change the structure of DNA. Once DNA is changed (altered, mutated), it is passed on in this mutated form for all future generations. The free radical doesn't care about preserving a human cell or DNA, it only wants its missing part. Ravaged atoms within the cell are now also missing a part, which creates a chain reaction unleashing free radical activity.
Examples of free radical damage or oxidation include rotting foods, rust that you might see on a car or lawn furniture. Often - as in the case of the oxidation of fats - this sets off chain reactions, with one radical causing the destruction of hundreds or thousands of previously normal molecules. Iron-triggered free radical activity can contribute to liver disease, pancreatic "burn out" (type II diabetes), joint disease, heart disease, neurological problems, and accelerate aging.
Antioxidants protect the body from free radical damage. An antioxidant donates or gives up the sought after electron to a free radical and renders it harmless. Our bodies contain antioxidants obtained from fresh fruits and vegetables in our diets. When our diets these foods or are high in fats and sugars especially in the presence of too much iron, we can have increased of free radical activity.
Iron that is not absorbed
For those with normal iron metabolism, unabsorbed iron, about 90% of iron ingested through diet, is taken up by specific cells in the intestinal tract, called enterocytes. These cells become engorged with iron, die, drop off, and are excreted in feces. For a time, however, as the excess iron makes its way through the colon, harmful pathogen such as a cancer cell or bacteria have an increased opportunity to be nourished by this abundant source of iron. Therefore, unless a person is actually iron deficient-which is determined by certain tests, he or she should not take iron supplements.
How much iron is in the body?
Males of average height have about 4 grams of iron in their body, females about 3.5 grams; children will usually have 3 grams or less. These 3-4 grams are distributed throughout the body in hemoglobin, tissues, muscles, bone marrow, blood proteins, enzymes, ferritin, hemosiderin, and transport in plasma.
About iron image 004: iron distribution
The greatest portion of iron in humans is in hemoglobin. Except in cases of great blood loss, pregnancy, or growth spurts, where larger amounts of iron are required, our bodies only need about 1 to 1.5 milligrams of iron per day to replace what is lost. Normal daily excretion of iron through urine, vaginal fluid, sweat, feces, and tears total about 1-1.5 milligrams, or the equivalent of what most of us require per day, to function normally.
Nature provides for these periods of increased iron needs by stepping up the amount of iron that is absorbed. This very elaborate regularly system can be observed in females who are menstruating, who will naturally increase the 1.5 milligrams that she usually absorbs up to 3-3.5 milligrams to replenish her iron stores. An unborn child in the third trimester and right before birth gets a tremendous amount of iron from the mother. This vast store of iron is in preparation for a spectacular period of rapid growth and will assure adequate iron is available for the first six months of life. For this reason newborns and infants have exceedingly high serum ferritin and Tsat% (transferrin/iron saturation percentage). The continued assurance of iron during this period is from breast milk or infant formulas. Thereafter, iron needs can be met with solid foods introduced to an infant at the appropriate time.
Recommendation daily Allowance (RDA):
The RDA for iron and all other nutrients is established by the Food and Nutrition Board of the National Academies. You may also see references to Dietary Reference Intakes (DRI), Estimated average requirement (EAR) Adequate intake (AI) level and Tolerable upper intake level (UL).
The RDA and the UL for iron: The RDA represents a daily nutrient intake goal for healthy individuals that should prevent deficiency disease in 97% of the healthy population.
Tolerable upper intake level (UL) These represent a ceiling -- the largest amount of a nutrient that healthy individuals can take each day without being placed at increased risk of adverse health effects or any kind of adverse reaction (negative side effect). The UL for iron is 45 milligrams per day, based on findings of adverse gastrointestinal effects, such as constipation and nausea, that can occur when consuming iron supplements, especially when taken on an empty stomach.
Iron Disorders Institute Scientific Advisory Board recommends that whenever possible iron should be gotten from food and not from supplements, unless a person is determined to be iron deficient by his or her physician. Children, females who are pregnant or nursing and the elderly are among the groups of people who are often inappropriately given iron supplements. The dangers of too much iron in a person's system have been linked with numerous health problems. Before anyone consumes iron pills iron deficiency anemia should be confirmed by a physician with specific tests. People with even mild infections can appear to be iron deficient, when in fact their body is withholding iron allowing just enough for body processes while assuring harmful germs cannot get the metal. This condition is called anemia of chronic disease and is different from iron deficiency anemia. There are specific tests to help distinguish between these two conditions.
Insert image 005 IDA/ACD compare
Iron Pills:
"The use of iron pills as a tonic for the treatment of an undiagnosed anemia can never be condoned". Iron Deficiency: Misunderstood, misdiagnosed and mistreated. CK Arthur & JP Isbistor, Drugs 33: 171-182, 1987 Iron Disorders Institute Guide to Anemia Cumberland Press 2003.
Except for those with anemia of chronic disease due to inflammatory diseases or infections, replenishment of iron to correct anemia is appropriate. The underlying cause of anemia will dictate the best way to replenish iron stores: oral supplements, IV or injected iron, blood transfusion or diet modifications.
Moderately low iron reserves or mild anemia due to insufficient daily intake of iron might be corrected with diet first. If the diet fails to improve hemoglobin and ferritin, oral iron in the form of pills may be considered. Ferrous sulfate, ferrous fulminate, or ferrous gluconate are common forms of iron in pills, which are usually inexpensive.
The amount of elemental iron contained in iron pills will vary. A 325-mg supplement is probably made of ferrous fumarate or gluconate and actually contains only 100 mgs of elemental iron per pill, the balance of the mass being the fumarate or gluconate counter iron. For example:
Insert image 006 compounds
Carbonyl iron, which is contained in Feosol Caplet, Ferra-Cap and Icar-C Plus(tm) is often used by physicians because it is less toxic to children who might take an accidental overdose. Iron pills that contain heme iron such as Proferrin(tm) and VitaHeme(tm) are tolerated well. Renal disease patients who took Proferrin(tm), report that there were fewer side effects, such as gastro-intestinal discomfort (nausea, vomiting). Since heme is more easily absorbed, smaller amounts of iron are contained in a single dose of this type of iron pill.
About Proferrin(tm): Performance studies indicate that iron absorption rates are between 15% and 20% without erythropoietin (EPO) therapy and as high as 30% with EPO therapy even in patients with high serum ferritin values (>600 ng/ml). In one study, the change in serum iron from Proferrin(tm) was nearly 23 times greater than from an identical dose of ferrous fumarate. Also, study participants were able to tolerate up to 60 mgs per dose on an empty stomach with fewer gastrointestinal side effects; a common complaint from patients taking traditional oral iron preparations. An additional benefit of heme iron supplementation is that patients can take it with their meals, unlike ionic iron preparations, which must be taken on an empty stomach between meals. The FDA allowed the marketing of Proferrin in the United States in late 2000. It is available in both an over-the-counter at most Walgreen's Drugstores and prescription form.
Until 1999, in the United States, the vast majority of iron supplements were made with ferrous iron salts. That is, a positively charged iron and its counter ion (negatively charged counterpart). Popular and common counter ions are sulfate, gluconate and fumarate. Fumarate and Gluconate are carbon containing carboxylic acids.
Typically, the way these compounds are made is that pure iron, usually as iron filings, are dissolved in sulfuric or hydrochloric acid. Once dissolved, the counter ion is added and the pH is slowly adjusted back to neutrality. As this happens the iron is no longer soluble so it binds to the counter-ion and drops out of solution. The slurry is then dehydrated and the remaining dry matter is the iron salt.
The manufacture of these products gives an important clue as to how they work in the body. Once ingested, it is imperative that the stomach contains acid to dissolve the iron salt. If a person is taking antacids or H2 blockers such as cimetidine (tagamet or axid), their stomach will be "achlorhydric" - no acid in the stomach and the iron salt will not dissolve. As such the person will derive no benefit from the iron supplement.
There are a few specialty pharmacies around the country that make special iron tonics or capsules. The tonics are made as solutions that keep the iron soluble. This is done so that people won't have to worry about whether the pills dissolve in their stomachs - it's already in solution. These present some danger however because if the whole bottle is consumed by a child, a very real risk of overdose exists. Because the manufacturers know this, they generally make them with very low iron concentrations.
Other pharmacies add things like "intrinsic factor" or liver extract. Liver extract contain ferritin as well as some heme iron. The amount of iron in these preparations bound to heme is generally less than 1/2 milligram.
Intrinsic Factor (IF) was so named because of its essential role in helping vitamin B12 perform in its role to produce red blood cells. IF is present in gastric juice and performs its duty by binding to B12. Once bound, IF changes and becomes less susceptible to digestion and thereby protects B12 and allows for its absorption from gastric juice.
Most of us can get sufficient amounts of iron from daily diets that include a moderate amount of meat, because meat contains heme, which is easily absorbed by the body. However, some people need supplemental iron. Finding the right type and dose is an individual decision made between the patient and the physician.
Iron pills should be taken 2 hours before or after other medications. Iron can inhibit the effectiveness of thyroid medications, antibiotics and some antidepressant drugs. Foods and substances that can interfere with the absorption of iron include calcium, tannins, which are found in coffee, tea, grapes, red wine, purple or red rice, and bran fiber or chocolate. Iron supplementation is best taken two hours after consuming these substances.
Also, oral iron might be improved by taking a small amount of supplemental zinc. In one Japanese study, Dr. Soruku Nishiyama,of Kumamota University School of Medicine demonstrated that "...supplementing with both minerals (zinc and iron) is more effective than either alone...and that some prenatal anemia is due to a deficiency of zinc, not iron."
In this study, Dr. Nishiyama placed 38 pregnant women into three groups: 11 took 34 mg/day zinc, 10 received 100 mg iron, and 17 took both supplements for eight weeks. Taking either zinc or iron alone did not change the average RBC counts, but the combination did; it also raised average hemoglobin levels from 10.3 to 11.0g/dL.
Iron poisoning:
According to the University of California Poison Prevention Center, each year, there are over 3,500 iron poisonings in children under the age of 6 years. It is also one of the most frequent causes of poisoning death in children.
http://wellness.ucdavis.edu/safety_info/poison_prevention/poison_book/iron_poisoning.html
The US Centers for Disease Control and Prevention provides that iron is the most common cause of pediatric poisoning deaths reported to poison control centers in the United States. During 1991, for example 5144 ingestions of iron supplements were reported to poison control centers in the United States; 11 were fatal. Children aged less than 6 years accounted for 3578 (69.6%) ingestions of iron and nine of the deaths. In addition, 18,457 ingestions of iron in the form of multivitamin or combination preparations were reported; 16,021 (87%) occurred among children aged less than 6 years. During 1991, consumption of multivitamin preparations in the form of prenatal vitamins with iron caused two additional deaths among children aged 17 and 18 months.
Although a toxic dose of elemental iron is 30 mg/kg, and a fatal dose is typically more than 250 mg/kg, ingestion of doses as low as 60 mg/kg has resulted in death. More than 120 different iron-containing preparations are available by prescription and over-the-counter purchase. The children in this report each consumed approximately 30 tablets of iron supplements; the number of tablets associated with a toxic dose varies, depending on the form and amount of iron used. Although in three cases the iron supplement was a prescription item, the 60 mg per tablet dosage is also available in over-the-counter preparations. Ingestion of as few as five or six tablets of a high-potency preparation could be fatal for a 10-kg (22-lb) child.
Iron poisoning is characterized by four clinical stages. The first stage -- with a duration of up to 6 hours after ingestion -- is characterized by acute onset of gastrointestinal symptoms (i.e., vomiting and diarrhea) that may progress to shock, coma, seizures, and death. During stage two -- from 6 to 24 hours after ingestion -- patients may be asymptomatic; however, evaluation and treatment for iron poisoning should not be delayed. During stage three -- from 12 to 48 hours after ingestion -- there may be hepatic and renal failure and cardiovascular collapse. Stage four -- from 3 to 4 weeks after
ingestion -- may include gastrointestinal obstruction and hepatic cirrhosis.
The following measures may help prevent iron toxicity-associated deaths: 1) iron supplements should be prescribed in limited amounts and dosages and when medically indicated; 2) health-care providers and others who prescribe or dispense iron supplements should emphasize to parents the hazards of unintentional iron consumption by children; and 3) adults should be instructed in the proper use of child-resistant packages when they receive them. Other considerations include the need to re-evaluate the effectiveness of child-resistant packaging and warning labels; for example, because ingestion of a small number of iron tablets may cause toxicity, tablets packaged in child-resistant individual blister packs may limit the number of tablets a child can access. Iron tablets should be made less appealing to children by eliminating use of sugar coating or attractive colors. Finally, educational efforts should be aimed at persons who use iron supplements and who have young children at home.
http://www.cdc.gov/mmwr/preview/mmwrhtml/00019593.htm
David N. Juurlink led a Canadian research team to determine the incidence of iron poisoning in young children and the association with the birth of a sibling. Juurlink and his colleagues studied records for 40 children admitted to hospital for iron poisoning. Seventeen cases (42%) occurred within a year (before or after) a sibling's birth. Children whose mothers had given birth to a sibling were almost twice as likely as children whose mothers had not given birth to a sibling to be admitted for iron poisoning within 6 months of birth (adjusted odds ratio [OR] 1.9, 95% confidence interval [CI] 0.9 to 3.9). The postpartum year was associated with a consistently elevated risk, including an almost 4-fold increase in the risk of iron poisoning during the first postpartum month (adjusted OR 3.6, 95% CI 0.8 to 16.5).
Image 007 iron pills and candy Correspondence to: Dr. David N. Juurlink, Sunnybrook and Women's College Health Sciences Centre, Toronto ON
Text to accompany image 007: Resemblance of iron tablets to candy. At left, from top, ferrous sulfate 300 mg, ferrous fumarate 200 mg and ferrous gluconate 300 mg. These tablets contain 60, 66 and 36 mg of elemental iron respectively. Ingestion of as few as 10 ferrous sulfate tablets has been fatal in children. At right, popular candy-coated chocolates with similar appearance.
The amount of iron that will cause poisoning depends upon the size of the child. An 8-year-old may show no symptoms from an amount that would cause serious symptoms in a 3-year-old. Symptoms appear at doses greater than 10 mg/kg (based on the body weight of the child).
If you suspect that your child has consumed iron pills take the child to the emergency room right away. Do not stop to call the pediatrician's. The emergency room staff will contact the pediatrician for you once you arrive.
Image 008
Contact the American Association Poison Control Centers: 1-800-222-1222
http://www.aapcc.org/
More about iron poisoning in children:
http://www.kidsource.com/kidsource/content4/child.poison.fda.html
http://www.emedicine.com/ped/topic2835.htm
Treatment & Maintenance
Removing iron by phlebotomy (blood donation) Chelation therapy (chemical iron removal)
Iron can be removed from the body in two ways, by blood donation (phlebotomy) or chelation therapy (pharmachological removal).
A phlebotomy is a procedure used to remove blood from a person. It is the opposite of a transfusion, which is a way to give blood to a person. Those with hemochromatosis (HHC), also called iron overload disorder must have phlebotomies to remove the iron.
Excess iron in a person's body can cause damage to the liver, pancreas, pituitary, joints and heart. As a result of this damage, one can develop cirrhosis of the liver, diabetes, impotence, arthritis, and heart failure. Therefore, removing the excess iron as soon as possible is critical.
People can lose tiny amounts of iron by simply taking half an aspirin a day. But for those with serious iron overload, the phlebotomy is necessary because it removes about 250 milligrams of iron with each treatment. When iron stores are high, swift action to remove the excess is critical. When a patient is diagnosed and treatment is begun prior to serum ferritin greater than 1,000ng/mL, the risk of cirrhosis or liver cancer is less than 1%!
When tests indicate you have iron overload......Iron overload is determined by measuring serum ferritin, fasting serum iron and total iron binding capacity. From the latter two tests, the transferrin iron saturation percentage (Tsat%) is calculated. When serum ferritin and Tsat% are both elevated and the patient has a normal hemoglobin, iron overload is likely and phlebotomy treatments can commence. Therapeutic phlebotomies require a physician's prescription or an order for periodic phlebotomies so long as the hemoglobin rebounds and remains above 12.5g/dL.
An order might be written as follows: "Phlebotomize 500 cc once a week** if Hgb>12.5g/dL"
**period of time should reflect frequency desired.
Note for physicians:
For patients whose initial ferritinis greater than 1,000ng/mL, sf shouldbe evaluated every 4-6 weeks until loweredto 750ng/mL. Otherwise, serum ferritin can be checked periodically such as every 3-6 months to determine the patient's unloading pattern.
Where phlebotomy treatments are done.....Phlebotomies might be done at a blood donation center, as an outpatient in a hospital or even in a doctor's office. Your doctor will probably advise places that provide the treatment. Consider convenience of location, cost to do the phlebotomy, and how responsive the center is to your situation.
Once you have determined the facility that will provide treatment, a trip to the lab is required. Before the phlebotomy may be done, hemoglobin and hematocrit will be checked. Usually centers have labs on site; the results will be forwarded to the attending nurse.
Keep good records:
You may request a copy of lab work from the office manager in charge of records in the doctor's office. Obtaining lab results is highly recommended so that a journal may be compiled. Journals will become a valuable tool if you have to move to another town or seek treatment from another doctor. Knowing about your disorder and understanding the diagnostic process helps to speed recovery and avoid future health setbacks.
The Procedure:
After the preliminary tests for hemoglobin and hematocrit are finished, a nurse prepares you for the phlebotomy. Usually you will stretch out on a comfortable recliner chair. The nurse takes your blood pressure, temperature and heart rate (pulse). These numbers will be recorded on your medical chart for future reference. The nurse then waits for the lab to call with hemoglobin and hematocrit readings. After being notified levels are within a safe range, your arm will be prepared for bloodextraction.
An elastic band is tied around the upper part of the arm. This helps the vein to stand up. You may have to squeeze a soft rubber ball or make a fist several times to help the vein remain accessible. The nurse then swabs an iodine-based antiseptic on the vein and all around the area near the vein. This is to disinfect the area where the needle is to be inserted and to make certain no bacteria gets into your system during treatment.
A special needle is then inserted into the vein. You might feel a little pinch, but it lasts only a second. A piece of tape is placed over the needle to keep it stable; you just sit back and relax.
Some like to bring a headset with earphones or a good book to read during treatment. While relaxing, the blood flows from the needle, into a tube, and then into the blood bag. The blood bag sits on a special scale that measures the weight of the blood.
Myth #1
Taking two vials of blood from the arm is the same as a phlebotomy. Incorrect: a true phlebotomy treatment involves removal of about 500cc of blood or a full bag.
When the bag is sufficiently filled, about one pint, the phlebotomy is complete. The speed with which the blood bag fills depends on the thickness/thinness of your blood. Drinking adequate amounts of fluids for two weeks before the phlebotomy will help.
Myth #2
Iron can be removed by several methods. Misleading: although there are products that chelate with iron, nothing reduces high levels of tissue iron as efficiently as blood loss. Health food store products which claim to remove heavy metals cannot remove iron from ferritin. Only three methods to remove iron from the body efficiently and are used to therapeutically de-iron a patient.
- phlebotomy
- Desferrioxamine (Desferal) which is a chelator used for those with conditions of iron overload with anemia.
- Oral iron chelators and other pharmaceuticals will soon be on the US market for consideration in some cases.
While the blood is flowing out of your arm, you might think about all the iron that is leaving your system. About 250 mgs of iron are removed with each extraction. Think about how well you will be and the dreadful diseases you may avoid by having this procedure. You may be finished in as few as ten minutes or as many as thirty; again, it depends on your vein and thickness of your blood.
After the Treatment:
After the phlebotomy, the nurse will remove the needle from your arm. You may need to keep the area bandaged or you may need to apply mild pressure if bleeding continues. You should rest for about 20 minutes following therapy. This is a precaution to insure you do not get weak or dizzy. You may be given a snack while you are resting and it is suggested you eat something after your therapy.
Your blood will be discarded regardless of where you have the phlebotomy. HH blood is currently handled in the same way as contaminated blood. Efforts are being made to change this. Don't get frustrated or take it personally; your blood may be labeled contaminated, but you are not.
Between phlebotomies:
You might consider learning to drink at least eight glasses of water a day, taking extra B12 with folic acid and vitamin E. These supplements help to build red blood cells, which assure adequate hemoglobin and hematocrit levels. Your doctor should recommend the amount you take of these vitamins because the dosage will depend on your weight and age.
It is important to remember that just because a supplement is beneficial, taking more than the recommended dose does not provide a greater benefit; indeed, it may cause damage. Also, gulping great amounts of water prior to therapy is not wise; you may actually cause yourself to become water intoxicated, a serious condition. Use wisdom; implement diet changes slowly and with knowledge of the potential dangers associated with these changes.
Diet tips:
You also may consider eating more fiber, refrain from cooking in an iron skillet, and avoiding vitamin C at mealtime. Fiber impedes iron absorption while vitamin C enhances iron absorption. Drinking tea with meals is helpful as the tannin in tea also impedes iron absorption. Decaffeinated tea might be the better choice; some physicians believe that too much caffeine can be unhealthy. Eat foods like fruit and juice high in vitamin C between meals. You should be aware that tobacco is rich in iron and that inhalation of this smoke directly or second-hand is harmful to your lungs. See diet recommendations for patients with hemochromatosis.
Exercise is a good idea.....
Regular, intense exercise or taking aspirin daily will cause some blood loss and thus iron loss. However, you should consult your doctor before incorporating any of these practices into your daily routine. Aspirin can be dangerous for youths with fever and it can interact with some drugs. Your pharmacist may be able to provide you with drug interaction advise; if not, contact your doctor.
Each person responds to treatment in a unique way.You may need many phlebotomies or only a few. Much depends on age, the extent of saturation, ferritin levels, hemoglobin response, one's physical condition including symptoms, and the speed with which an individual unloads iron. Your physician will help to determine the frequency of phlebotomies.
Note: Ferritin drops by about 30-50ng/dL with each full unit of blood removed. Ferritin levels can be distorted. Individuals with liver damage such as cirrhosis will unload iron faster than those without liver damage. Other factors that may skew ferritin include presence of inflammation or infection. Checking ferritin periodically can be can protect against undue iron deficiency anemia caused by overbleeding.
Patients undergoing de-ironing are at risk for overbleeding that can take place in the latter part of de-ironing. Bleeding a patient until mild iron deficiency anemia is reached is out dated thinking. There is no known benefit to the forced-sustained anemia, a practice that was instituted nearly three decades ago. Iron Disorders Institute Scientific Advisory Board recommends against phlebotomy in patients whose hemoglobin is lower than 12.5g/dL. Physician guidelines for phlebotomies are available upon request from Iron Disorders Institute.
Prior to treatment, a patient will have demonstrated a fasting ferritin greater than 200ng/mL (females) or 300ng/mL (males) with an accompanying transferrin iron saturation percentage value greater than 45%. Physicians may request a copy of the Iron Disorders Institute Scientific Advisory Board Hemochromatosis Diagnosis Algorithm Reference Chart.
Frequency of phlebotomies will vary: When ferritin is above 1000ng/mL phlebotomy treatments will be aggressive usually as frequent as twice weekly while tolerable and until ferritin drops below 1000ng/mL.
Once serum ferritin is below 500ng/mL, the frequency of treatment may slow down from twice weekly to once a week or even to every other week depending upon the patient's condition, behavior (eating habits) and ability to unload iron.
During de-ironing: blood contains water and other nutrients. Adequate fluid intake guards against dehydration. Patients are encouraged to take a one-a-day multi-vitamin without iron to support the loss of nutrients. Look for vitamins with minerals (except iron) and B complex.
Once the ferritin is within the range of 25-75ng/mL, the patient may donate blood routinely as defined by attending physician for optimum quality of health or may have periodic therapeutic phlebotomy by doctor's order. Frequency of donation or therapeutic phlebotomy will depend upon patient's Personal Health Profile as observed by patient and attending physician: age, weight, response to treatment, symptoms, rate of iron unloading and general physical condition.
At anytime during treatment you experience symptoms of heart irregularities or severe abdominal pain or symptoms of anemia, alert your physician immediately.
Symptoms of anemia can often be mistaken by a patient as symptoms of iron overload. Symptoms of anemia or iron overload can include: fatigue, heart arrhythmia, headache, sensitivity to cold, shortness of breath, dizziness and restless legs syndrome. Lab tests are needed to distinguish between the two.
The recovery phase of treatment...
Recovery is a period of time when the patient has been adequately de-ironed and symptoms have diminished. Unfortunately, it is possible that not all symptoms will disappear. If excess iron has had enough time to damage critical organs, one may never restore these damaged organs to full function. Iron damage to the pituitary is not known to be reversible.
During the recovery phase, one must be attentive to any sign of repeat symptoms. So long as a patient remains symptom-free, the doctor will re-test iron levels about every 3 months. The initial three-month exam following recovery will provide a baseline or the first set of numbers after a series of phlebotomies whereby a person's pattern of un-loading can be established. These numbers are very important to the management of iron balance.
A person's length of recovery period, treatment and maintenance program is determined by how often that person must have a phlebotomy to keep iron levels in a normal range.
Maintenance patients are those who have reached normal iron ranges and who can remain within those normal ranges by donating blood periodically.
Most blood donation centers allow one donation every eight weeks. If you are a candidate for maintenance, then a periodic blood donation will suffice. If you are found to need treatment, needing more than one extraction in eight weeks, the attending physician will provide you with the necessary order for additional phlebotomies. Your gastroenterologist or hematologist may refer you back to your family physician for the maintenance phase of your therapy. Afterwards, you may resume a normal, happy healthy life with only a small adjustment to your schedule: a life-saving, blood donation every 8 to 10 weeks.
Chelation therapy
Chelate is from the Greek word "claw".
Patients who have anemia and iron overload at the same time cannot tolerate phlebotomy because their hemoglobin is not sufficient. These patients need chelation therapy to remove the iron.
Patients with sickle cell anemia, thalassemia major, and some forms of cancers who require repeated blood transfusions can develop transfusional iron overload. Each unit of blood used in transfusion contains about 250 milligrams of iron. The body cannot excrete iron, except in tiny amounts-about one milligram per day, which is sloughed off in skin or perspiration. Therefore the excess iron is trapped in the body. Over time the excess iron builds up in vital organs such as the anterior pituitary, heart, liver, pancreas and joints. Damage to these organs caused by the excess iron can result in organ failure and diseases such as diabetes, cirrhosis, osteoarthritis, heart attack, and hormone imbalances. Hypothyroidism, infertility, sterility, can result from these hormone imbalances and the patient can experience symptoms of chronic fatigue, mood swings, loss of sex drive, confusion, and memory loss.
In some cases the organ damage is irreversible; therefore, it is important to remove the unnecessary iron before damage can occur. Iron reduction is accomplished with chelation therapy, which is the removal of iron pharmacologically with an iron-chelating agent such as desferrioxamine, brand name Desferal. This is a drug especially formulated to bind with iron so that the iron can be excreted in urine.
The type of chelation therapy used to de-iron patients should not be confused with EDTA (ethylenediaminetetra-acetic acid), a method used by some alternative medicine practitioners. EDTA is a broad-spectrum chelator, meaning that it binds with and removes a wide number of minerals, including iron, but it is not specific. In contrast, desferrioxamine and deferiprone, a new oral chelator awaiting FDA approval, are highly specific for iron.
Desferal is not absorbed in the intestinal tract, therefore, this drug must be administered intravenously, which is done in an infusion center or hospital or subcutaneously, which is done using a portable battery-operated infusion pump. Generally, the pump is worn at night, where slow infusion of the iron chelating agent is administered over a period of about eight hours, for a duration of four to six nightly infusions per week. Patients are given a step-by-step demonstration of how to sterilize the skin, insert the needle and operate the pump.
Before Desferal is administered by either method, a test dose is given to be certain that there are no immediate reactions to the drug. Desferal is administered slowly at first, beginning with 1.0 gram, three to four times per week with monitoring of iron excretion in a cumulative 24-hour urine sample. If effective, the dose can then be adjusted upwards, one gram at a time, up to four times per week, until the patient reaches a tolerable level. The dose should not to exceed 50 milligrams/kg weight, or about 3 grams per day. Periodic examination of the patient is necessary until positive response to treatment is confirmed.Patients might be given an additional two grams of Desferal intravenously for each unit of blood transfused. Desferal is injected separately from blood transfusions.
Desferal has been approved for use in the USA since the late 1970's. Deferiprone also called L1, brand name Ferriprox is different from Desferal in that Ferriprox can be taken orally. In August of 1999, Apotex Inc., the Canadian Pharmaceutical Manufacturer of Ferriprox was granted approval in Europe by the European Agency For the Evaluation of Medicinal Products to use the oral chelator for treatment of iron overload in patients with thalassemia when desferrioxamine therapy is contraindicated or in those who develop serious toxicity with desferrioxamine therapy. Ferriprox will be submitted to the FDA in September 2002 to be approved for use in the USA.
Scientists have different opinions about the safety of deferiprone. Dr. Nancy Olivieri at Toronto's Hospital for Sick Children studied deferiprone in 19 patients to determine its effectiveness to remove tissue iron. She concluded that L1 was more efficient than Desferal in the first few days of application, but when used for periods longer than two weeks, the outcome for the patients in participating in her study was poor. Some of these patients developed increased liver disease.
Other scientists who have studied deferiprone have found that it is not as effective removing liver iron as Desferal, but that it is better than Desferal in the removal of iron in the heart. One team of investigators in Great Britain lead by Dr. D.J. Pennell compared iron content in the hearts of 15 patients receiving long-term deferiprone treatment to 30 patients with thalassemia major who were on long-term Desferal therapy. Specialized MRI's of the livers and hearts of these patients were obtained. Investigators concluded from their findings that the deferiprone group had significantly less heart iron and better heart function (higher ejection-fractions) than the patients on Desferal.
Studies conducted by Italian, German, and Australian scientists substantiate that Desferal is more efficient removing iron from the liver, where deferiprone is more efficient removing iron from the heart. This would indicate that a combination of these two drugs might be a better overall therapy for patients with concurrent anemia and iron overload.
The primary role of iron-chelation therapy is to prevent premature death from heart attack due to myocardial iron overload. Statistically 50% of patients with thalassemia major die of heart attack before the age of 35, primarily due to iron-related heart failure.
Side effects:
The urine can become orange colored, which is a harmless side effect. Immediate symptoms of adverse reaction to Desferal chelation therapy might include: visual disturbances, blurred vision, rash or hives, itching, vomiting, diarrhea, stomach or leg cramps, fever, rapid heart beat, hypotension (low blood pressure), dizziness, anaphylactic shock, and pain or swelling at site of intravenous entry. Long term problems might include kidney or liver damage, loss of hearing or cataracts.
Patients should report such symptoms immediately to their physician who can adjust dosage. Further, physicians might examine patients visual status with slit-lamp fundoscopy (means of examining the eye) and hearing status with audiometry or hearing test. Liver enzymes (ALT, AST, GGT and ALP), a kidney function test such as BUN, serum ferritin and transferrin iron saturation percentage might also be measured by the attending physician.
Pumps used for chelation therapy:
A variety of pumps are available such as the CADD Micro, manfactured by Sims Deltec, the Grasby pump, the Microjet Crono Ambulatory Infusion Pump and The Eclipse C-Series Continuous Infusion System are among the types of equipment that can be used. Each has special features and benefits such as size, portability and cost. Patients might like to contact organizations such as Cooley's Anemia Foundation or the Iron Disorders Institute for patient comments about their experiences with the various types of equipment.
Also there are a number of needles available. Straight needles, butterfly, or thumbtack (also called button) or devices such as the MiniMed Sof-serter. The Sof-serter is a bit different from the other needles in that a spring-activated device inserts a tiny plastic catheter under the skin for infusion; the needle is removed after insertion.
Each patient is different and physicians can talk about the features and benefits of the various pumps and needles, such as size, portability, ease in operation, etc.
Tips:
Emla cream can be used prior to inserting the needle. This cream is a mild topical anesthetic which somewhat numbs the skin so that the patient does not feel the needle stick.
Patients should discuss the need for daily supplementation with vitamin C and E, selenium, B-complex and other nutrients. Also, maintaining proper hydration is important for anyone on chelation therapy.
Limitations of Desferal
Nursing mothers will need to talk with their physicians. It is not known how much of the drug gets into breast milk; thus, a mother who is receiving Desferal treatment might consider low iron soy formula substitutes.
Immediate symptoms of adverse reaction to Desferal chelation therapy might include: visual disturbances, blurred vision, rash or hives, itching, vomiting, diarrhea, stomach or leg cramps, fever, rapid heart beat, hypotension (low blood pressure), dizziness, anaphylactic shock, and pain or swelling at site of intravenous entry. Long term problems might include kidney or liver damage, loss of hearing or cataracts.
Patients should report such symptoms immediately to their physician who can adjust dosage. Further, physicians might examine patients visual status with slit-lamp fundoscopy (means of examining the eye) and hearing status with audiometry or hearing test. Liver enzymes (ALT, AST, GGT and ALP), a kidney function test such as BUN, serum ferritin and transferrin iron saturation percentage might also be measured by the attending physician.
When to begin iron chelation therapy
Initiating chelation therapy depends upon several factors: the patient's overall health, hematologic values, especially hemoglobin, hematocrit and the tissue iron levels.
Tissue iron is determined by measuring serum ferritin, and fasting serum iron and TIBC (total iron-binding capacity). These results help the physician to monitor iron build up and to address the excess iron as soon as possible. Some physicians will begin chelation therapy when serum ferritin is between 1,000-1,500ng/mL. Serum ferritin should not be allowed to go above 2,500 ng/mL before beginning chelation.
Oral chelators: Apotex, a Canadian company produces deferiprone as brand name Ferriprox, which is available in Canada and Europe. Novartis Pharmaceuticals produces ICL670 or brand name EXJADE(R), which will soon be available in the US market.
Other chelators: Biomedical Frontier's (BMF) starch-based synthetic chelator is a product used intravenously similar to Desferal, but BMF's product requires only a single dose that takes about an hour to administer to achieve similar results as one week of Desferal therapy, which requires five to six nightly infusions lasting eight to twelve hours per infusion. The BMF product must be administered with medical supervision, but a once a week trip to an infusion center may be an appealing alternative to the portable pump.
Maintaining iron balance with the diet for patients with hemochromatosis
It is not necessary to become a fanatic about label reading or go to extremes with one's diet. Some very good common sense measures can assure adequate iron for the person with iron deficiency anemia and control of iron absorption for people with iron loading conditions.
The basics of iron balance through diet are to periodically include or avoid certain foods, additives, and supplements.
Recommendations for patients trying to cut down on iron absorption:
- limit red meat consumption to three or fewer portions per week: meat contains the most easily absorbable form of iron: heme iron but red meat is also an excellent source of protein, B12, and zinc. Eliminating red meat from the diet entirely is not necessary providing a patient is compliant with therapy and routinely seeing a physician who is monitoring iron levels.
- drink tea or coffee with a meal-unless there is evidence of liver damage or disease. Tea and coffee tannin which inhibits iron absorption
- limit alcohol consumption or abstain altogether if there is liver damage: alcohol enhances the absorption of iron. For those without liver damage moderate consumption of alcohol is allowed.
- avoid consumption of vitamin C supplements with the meal: vitamin C enhances the absorption of iron. Limit doses of supplemental vitamin C to 200 milligrams if possible. Vitamin C should not be eliminated from the diet.
- eat plenty of fresh fruits and vegetables regardless of the vitamin C content: fruits and vegetables contain antioxidants which protect a person from free radical damage. Iron is a know trigger of free radical activity.
- maintain a good schedule of blood donation: many hemochromatosis patients forget to have a phlebotomy. Keeping a schedule or note in a prominent place is helpful. If ferritin levels get too high, a person may have to move from routine maintenance back into therapeutic frequency.
Insert image heme content in meats
Insert image foods that inhibit
There are other foods that inhibit the absorption, but these can be used in moderation or not at all depending upon the patient's iron load. A word of caution: some hemochromatosis patients have become so efficient at inhibiting the absorption of iron that they become iron avid. The iron avid patient has a normal to low ferritin (usually low) but a very high transferrin-iron-saturation percentage (Tsat%). Experts agree that iron avidity is probably the body's response to not enough iron coming into the system. Hemochromatosis patients who have become iron avid, should discontinue phlebotomies and eat to replenish iron stores.
Maintaining iron balance in patients with iron deficiency anemia
Unless a patient is a vegetarian or has a condition that affects absorption, such as Crohn's, low stomach acid or a B12 or folate deficiency he or she can get plenty of iron by increasing consumption of red meat. Adding vitamin C and beta-carotene rich foods (not supplemental beta-carotene) can also enhance the absorption of iron.
All nutrients are important to normal metabolism, but some are key. B12, B6 (folate), zinc and copper must be present in adequate amounts because iron is dependent on these for absorption and transport.
Iron, zinc, copper, B12 and folate are essential to red blood cell production. These minerals work in unison, and excesses in any of one of them will deplete stores of the other two. Often when there is an iron deficiency there will be a zinc deficiency at the same time. Unless a physician specifically looks at zinc levels, the deficiency may be determined as insufficient iron and treated will not be complete.
As with any supplementation, moderation is important. High doses of supplemental zinc can interfere with copper utilization. This imbalance in copper can lead to impaired metabolism of iron because iron cannot be transported or utilized without copper. Therefore a copper deficiency results in iron deficiency anemia. High levels of zinc, iron, calcium and manganese interfere with copper absorption. Deficiencies in copper can result in auditory hallucinations, depression and may contribute to binge and purge eating disorders.
The copper RDA for adults is 0.9 mg daily. A slightly higher amount is recommended during pregnancy, and 1.3 mg daily is recommended for mothers who breast-feed. A high copper intake adversely effects zinc absorption, and thus dosage recommendations for copper consider dosages for zinc. The optimal ratio of zinc to copper is 10:1 or 10 milligrams of zinc to 1 milligram of copper.
Copper excess is seen in Wilson's disease, a condition that leads to serious liver damage. According to recent USDA surveys, the average intake of copper by women 19 to 50 years of age was about 1 milligram, and men of the same age was about 1.6 milligrams. For women, this amount is less than the 1.5- to 3-milligram range of Estimated Safe and Adequate Daily Dietary Intakes recommended by the Food and Nutrition Board of the National Academy of Sciences. Shellfish, legumes and nuts are good sources of copper.
Calcium is another mineral that can interfere with absorption of iron. Dairy products or supplements with more than 300 milligrams of calcium can diminish iron absorption. Calcium in amount of 600 milligrams or more can impair the absorption of heme iron. One cup of skimmed milk contains about 300 milligrams of calcium.
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