Iron Deficiency Anemia
Iron deficiency anemia is a common type of anemia — a condition in which blood lacks adequate healthy red blood cells. Red blood cells carry oxygen to the body’s tissues.
Symptoms:
Initially, iron deficiency anemia can be so mild that it goes unnoticed. But as the body becomes more deficient in iron and anemia worsens, the signs and symptoms intensify.
Iron deficiency anemia signs and symptoms may include:
- Extreme fatigue
- Weakness
- Pale skin
- Chest pain, fast heartbeat, or shortness of breath
- Headache, dizziness or lightheadedness
- Cold hands and feet
- Inflammation or soreness of your tongue
- Brittle nails
- Unusual cravings for non-nutritive substances, such as ice, dirt or starch
- Poor appetite, especially in infants and children with iron deficiency anemia
Causes:
Blood loss. Blood contains iron within red blood cells. So, if you lose blood, you lose some iron. Women with heavy periods are at risk of iron deficiency anemia because they lose blood during menstruation. Slow, chronic blood loss within the body — such as from a peptic ulcer, a hiatal hernia, a colon polyp or colorectal cancer — can cause iron deficiency anemia. Gastrointestinal bleeding can result from regular use of some over-the-counter pain relievers, especially aspirin.
A lack of iron in your diet. Your body regularly gets iron from the foods you eat. If you consume too little iron, over time your body can become iron deficient. Examples of iron-rich foods include meat, eggs, leafy green vegetables and iron-fortified foods. For proper growth and development, infants and children need iron from their diets, too.
An inability to absorb iron. Iron from food is absorbed into your bloodstream in your small intestine. An intestinal disorder, such as celiac disease, which affects your intestine’s ability to absorb nutrients from digested food, can lead to iron deficiency anemia. If part of your small intestine has been bypassed or removed surgically, that may affect your ability to absorb iron and other nutrients.
Without iron supplementation, iron deficiency anemia occurs in many pregnant women because their iron stores need to serve their own increased blood volume as well as be a source of hemoglobin for the growing fetus.
Risk factors:
These groups of people may have an increased risk of iron deficiency anemia:
- Because women lose blood during menstruation, women in general are at greater risk of iron deficiency anemia.
- Infants and children. Infants, especially those who were low birth weight or born prematurely, who don’t get enough iron from breast milk or formula may be at risk of iron deficiency. Children need extra iron during growth spurts. If your child isn’t eating a healthy, varied diet, he or she may be at risk of anemia.
- People who don’t eat meat may have a greater risk of iron deficiency anemia if they don’t eat other iron-rich foods.
- Frequent blood donors Without iron supplementation, two-thirds of the donors had not recovered the iron they lost, even after 24 weeks.
- People with cancer
- Up to 60% of patients with colon cancer have iron deficiency at diagnosis, probably due to chronic blood loss.
- People who have gastrointestinal disorders or have had gastrointestinal surgery.
- People with certain gastrointestinal disorders (such as celiac disease, ulcerative colitis, and Crohn’s disease) or who have undergone certain gastrointestinal surgical procedures (such as gastrectomy or intestinal resection) have an increased risk of iron deficiency because their disorder or surgery requires dietary restrictions or results in iron malabsorption or blood loss in the gastrointestinal tract.
- People with heart failure.
- Approximately 60% of patients with chronic heart failure have iron deficiency and 17% have IDA, which might be associated with a higher risk of death in this population. Potential causes of iron deficiency in people with heart failure include poor nutrition, malabsorption, defective mobilization of iron stores, cardiac cachexia, and use of aspirin and oral anticoagulants, which might result in the loss of some blood in the gastrointestinal tract.
IDA (Iron Daily Administration) in pregnant women:
The Centers for Disease Control and Prevention (CDC) recommends that all pregnant women, at their first prenatal visit, begin taking an oral, low dose (30 mg/day) supplement of iron and be screened for IDA . Women with IDA (which it defines as a hemoglobin concentration less than 9 g/dL or a hematocrit level less than 27%) should be treated with an oral dose of 60-120 mg/day of iron.
Anemia of chronic disease:
Certain inflammatory, infectious, and neoplastic diseases (such as rheumatoid arthritis, inflammatory bowel disease, and hematologic malignancies) can cause anemia of chronic disease, also known as anemia of inflammation. Anemia of chronic disease is the second most common type of anemia after IDA. In people with anemia of chronic disease, inflammatory cytokines upregulate the hormone hepcidin. As a result, iron homeostasis is disrupted and iron is diverted from the circulation to storage sites, limiting the amount of iron available for erythropoiesis.
People on dialysis:
Many people who are on kidney dialysisneed extra iron. The kidneys are responsible for making erythropoietin, a hormone that tells the body to make red blood cells. If the kidneys don’t work as well, anemia is often a side effect.
You may lose a small amount of blood during dialysis. And dialysis diets also often limit iron intake. Some medications that people on dialysis take can use up iron or interfere with the body’s ability to absorb it.
A practical approach to anemia Size of RBCs:
– MCV (Mean Cell Volume)
Microcytic < 80 fl Normocytic 80-100 fl Macrocytic > 100 fl
Differential diagnosis of microcytic anemia
Iron deficiency:
Anemia of chronic disease
- Thalassemias
- Hemoglobinopathies
- Hereditary spherocytosis
- Hereditary X-linked sideroblastic anemia
- Lead poisoning (usually mild microcytosis)
- Iron deficiency anemia
- Common nutritional deficiency
- Bleeding is a leading cause of iron deficiency anemia.
Iron facts:
Body iron:
80% functional (Hgb, myoglobin, cytochromes, etc.)
20% storage
– Absorption: primarily in the duodenum
– Transferrin: transports iron in blood – Ferritin: storage form of iron
– Hemosiderin: derived from ferritin, long-term storage of iron
MCH: Mean Cell Hemoglobin
MCHC: Mean Cell Hemoglobin Concentration
Lab studies in iron deficiency anemia:
Microcytic, hypochromic anemia
– Decreased MCV, MCH, & MCHC
Iron studies:
– Low serum iron
– High total iron binding capacity (TIBC, transferrin concentration)
– Low % transferrin saturation
– Low ferritin
– Decreased bone marrow storage iron (hemosiderin)
As a component of myoglobin, another protein that provides oxygen, iron supports muscle metabolism and healthy connective tissue. Iron is also necessary for physical growth, neurological development, cellular functioning, and synthesis of some hormones.
Dietary iron has two main forms: heme and nonheme. Plants and iron-fortified foods contain nonheme iron only, whereas meat, seafood, and poultry contain both heme and nonheme iron.
Most of the 3 to 4 grams of elemental iron in adults is in hemoglobin.
Much of the remaining iron is stored in the form of ferritin or hemosiderin (a degradation product of ferritin) in the liver, spleen, and bone marrow or is located in myoglobin in muscle tissue. Transferrin is the main protein in blood that binds to iron and transports it throughout the body. Humans typically lose only small amounts of iron in urine, feces, the gastrointestinal tract, and skin. Losses are greater in menstruating women because of blood loss. Hepcidin, a circulating peptide hormone, is the key regulator of both iron absorption and the distribution of iron throughout the body, including in plasma.
Iron deficiency progresses from depletion of iron stores.
Serum ferritin concentration, a measure of the body’s iron stores, is currently the most efficient and cost-effective test for diagnosing iron deficiency.
However, serum ferritin is subject to influence by inflammation (due, for example, to infectious disease), which elevates serum ferritin concentrations.
The RDAs for vegetarians are 1.8 times higher than for people who eat meat. This is because heme iron from meat is more bioavailable than nonheme iron from plant-based foods, and meat, poultry, and seafood increase the absorption of nonheme iron.
Recommended Dietary Allowances (RDAs) for Iron:
- Infants 0-6 months 0.27 mg
- Infants 7-12 months 11 mg
- Children 1-3 years 7 mg
- Children 4-8 years 10 mg
- Children 9-13 years 8 mg
- adolescents Male 14-18 years 11 mg
- Adolescent females 14-18 years 15 mg
- Adult males 19-50 years 8 mg
- Adult females 19-50 years 18 mg
- Persons 51 years or older 8 mg
- Pregnant woman 27 Lactating adolescent 10 mg
- Breastfeeding women 9 mg
Sources of Iron
Food:
Breast milk contains highly bioavailable iron but in amounts that are not sufficient to meet the needs of infants older than 4 to 6 months.
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Heme Iron Foods:
- Liver
- Oysters, clams and mussels
- Red meats such as beef and lamb
- Canned sardines
- Chicken and turkey
- Pork and ham
- Veal
- Fish
Nonheme Iron Foods:
- Iron-fortified breakfast cereals, rice, breads and pastas
- Cooked beans and lentils
- Pumpkins, squash or sesame seeds
- Chickpeas, kidney beans and lima beans
- Dried apricots
- Baked potatoes
- Nuts
- Tofu
- Broccoli stems
- Raw and cooked spinach and kale
- Peas
- Green leaves.
Sorry Popeye, spinach DOESN’T make your muscles big: Expert reveals sailor’s love of the food was due to a misplaced decimal point.
The iron content of spinach was miscalculated by a German chemist when he misplaced a decimal point
While there are just 3.5 milligrams of iron in a 100g serving of spinach, the accepted number became 35 milligrams thanks to his mistake
This caused the popular misconception that spinach is exceptionally high in iron, which makes the body stronger.
The connection between the incorrect calculation and popular cartoon character has been made in a book by scientist Samuel Arbesman.
_To help extract the most amount of iron out of a food, it’s advisable to eat it along with something high in vitamin C such as:
- Oranges
- Lemons
- Broccoli
- Leafy greens
- Melon
- Kiwi
- Peppers
- Strawberries
- Tomatoes
Dietary supplements:
Iron is available in many dietary supplements. Multivitamin/multimineral supplements with iron, especially those designed for women, typically provide 18 mg iron (100% of the DV). Multivitamin/multimineral supplements for men or seniors frequently contain less or no iron. Iron-only supplements usually deliver more than the DV, with many providing 65 mg iron (360% of the DV).
Frequently used forms of iron in supplements include ferrous and ferric iron salts, such as ferrous sulfate, ferrous gluconate, ferric citrate, and ferric sulfate. Because of its higher solubility, ferrous iron in dietary supplements is more bioavailable than ferric iron. High doses of supplemental iron (45 mg/day or more) may cause gastrointestinal side effects, such as nausea and constipation. Other forms of supplemental iron, such as heme iron polypeptides, carbonyl iron, iron amino-acid chelates, and polysaccharide-iron complexes, might have fewer gastrointestinal side effects than ferrous or ferric salts.
The different forms of iron in supplements contain varying amounts of elemental iron. For example, ferrous fumarate is 33% elemental iron by weight, whereas ferrous sulfate is 20% and ferrous gluconate is 12% elemental iron. Fortunately, elemental iron is listed in the Supplement Facts panel, so consumers do not need to calculate the amount of iron supplied by various forms of iron supplements.
Calcium might interfere with the absorption of iron, although this effect has not been definitively established. For this reason, some experts suggest that people take individual calcium and iron supplements at different times of the day.
Parenteral Iron Therapy:
Parenteral iron therapy is occasionally necessary for patient’s intolerant or unresponsive to oral iron therapy, for receiving recombinant erythropoietin therapy, or for use in treating functional iron deficiency. There are now three parenteral iron products available: iron dextran, ferric gluconate, and iron sucrose.
Iron Dextran
One of the advantages of iron dextran is the ability to infuse the patient’s total iron requirement in one administration (total-dose infusion). Clinicians can conveniently treat patients in a single hospital or clinic visit with this product. However, this method has been associated with a higher incidence of adverse events. Delayed reactions of hypotension, arthralgias, myalgias, malaise, abdominal pain, nausea, and vomiting have followed total dose infusion. A 25-mg test dose should be given to all new patients started on iron dextran. Patients should be monitored for adverse effects for 1 hr after a test dose. Uneventful test doses do not exclude a patient from experiencing hypersensitivity reactions with the first dose or subsequent doses.
The rate of infusion should not exceed 50 mg/ min.
Sodium Ferric Gluconate Complex in Sucrose Injection:
administration is by intravenous injection or infusion. The rate of administration should not exceed 12.5 mg/min.
Iron Sucrose Injection:
The rate of administration should not exceed 20 mg per minute.
people with iron deficiency usually have other nutrient deficiencies.
Iron depletion and deficiency progresses through several stages:
Mild deficiency or storage iron depletion: Serum ferritin concentrations and levels of iron in bone marrow decrease.
Marginal deficiency, mild functional deficiency, or iron-deficient erythropoiesis (erythrocyte production): Iron stores are depleted, iron supply to erythropoietic cells and transferrin saturation decline, but hemoglobin levels are usually within the normal range.
IDA: Iron stores are exhausted; hematocrit and levels of hemoglobin decline; and the resulting microcytic, hypochromic anemia is characterized by small red blood cells with low hemoglobin concentrations.
Health Risks from Excessive Iron
Adults with normal intestinal function have very little risk of iron overload from dietary sources of iron. However, acute intakes of more than 20 mg/kg iron from supplements or medicines can lead to gastric upset, constipation, nausea, abdominal pain, vomiting, and faintness, especially if food is not taken at the same time. Taking supplements containing 25 mg elemental iron or more can also reduce zinc absorption and plasma zinc concentrations. In severe cases (e.g., one-time ingestions of 60 mg/kg), overdoses of iron can lead to multisystem organ failure, coma, convulsions, and even death.
Some groups are at risk of obtaining excess iron. Individuals with hereditary hemochromatosis, which predisposes them to absorb excessive amounts of dietary iron, have an increased risk of iron overload.
Hemochromatosis, a disease caused by a mutation in the hemochromatosis (HFE) gene, is associated with an excessive buildup of iron in the body. About 1 in 10 whites carry the most common HFE mutation (C282Y), but only 4.4 whites per 1,000 are homozygous for the mutation and have hemochromatosis. The condition is much less common in other ethnic groups. Without treatment by periodic chelation or phlebotomy, people with hereditary hemochromatosis typically develop signs of iron toxicity by their 30s. These effects can include liver cirrhosis, hepatocellular carcinoma, heart disease, and impaired pancreatic function. The American Association for the Study of Liver Diseases recommends that treatment of hemochromatosis include the avoidance of iron and vitamin C supplements.
Interactions with Medications:
Iron can interact with certain medications, and some medications can have an adverse effect on iron levels. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their iron status with their healthcare providers.
Iron may decrease the absorption of:
_Oral bisphosphonates (eg, alendronate, clodronate, etidronate, ibandronic acid, risedronate, tiludronate). Do not take iron within 2 hours of taking an oral bisphosphonate.
_Levodopa / carbidopa
Some evidence indicates that in healthy people, iron supplements reduce the absorption of levodopa (found in Sinemet® and Stalevo®), used to treat Parkinson’s disease and restless leg syndrome, possibly through chelation. In the United States, the labels for levodopa warn that iron-containing dietary supplements might reduce the amount of levodopa available to the body and, thus, diminish its clinical effectiveness. Separate dosage times by as long as possible.
_Methyldopa. Separate dosage times by 2 hours; monitor BP and adjust methyldopa dose if necessary.
_Penicillamine: Penicillamine is an anti-rheumatic drug and used for treating Wilson’s disease. Give iron at least 2 hours before penicilammine
_Levothyroxine. Levothyroxine (Levothroid®, Levoxyl®, Synthroid®, Tirosint®, and Unithroid®) is used to treat hypothyroidism, goiter, and thyroid cancer. The simultaneous ingestion of iron and levothyroxine can result in clinically significant reductions in levothyroxine efficacy in some patients. The labels for some of these products warn that iron supplements can reduce the absorption of levothyroxine tablets. Separate dosage times by 4–5 hours
Iron absorption may be decreased by:
_Proton pump inhibitors.
Gastric acid plays an important role in the absorption of nonheme iron from the diet. Because proton pump inhibitors, such as lansoprazole (Prevacid®) and omeprazole (Prilosec®), reduce the acidity of stomach contents, they can reduce iron absorption.
_Antacids. Separate dosage times by as long as possible
_Calcium (eg, in dairy products such as milk). Separate dosage times by several hours
_Phytates (eg, whole grain cereals). Separate dosage times by several hours
_Tea and coffee. Separate dosage times by several hours
Iron absorption may be increased by:
Chloramphenicol
Systemic chloramphenicol increases serum iron concentration due to chloramphenicol-induced bone marrow toxicity; if myelosuppression occurs, monitor iron stores, and decrease iron dose as needed; consider stopping chloramphenicol, seek specialist advice.
Iron absorption is decreased by, and iron decreases the absorption of:
Oral quinolones (antibiotic) (eg, ciprofloxacin, moxifloxacin, norfloxacin)
Take quinolone at least 2 hours before iron.
Tetracyclines (antibiotic) (eg, doxycycline, minocycline)
Separate dosage times by as long as possible (at least 2 hours)
Presented by Pharmacist Ruba noueddin
1_ https://www.mayoclinic.org/diseases-conditions/iron-deficiency-anemia/symptoms-causes/syc-20355034
2_https://arup.utah.edu/media/anemia/Anemia%20Lecture%20for%20the%20MLT%20students.pdf
3_ https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/#en69
4_ https://hemophilianewstoday.com/2018/03/01/33-iron-rich-foods-add-diet-2/