Perhaps it is just a case of missing the forest for the trees.
“Anna isn’t anemic anymore,” her doctor told me. “Her hemoglobin is fine. There is no need to give her more iron.”
But Anna consulted a hematologist who viewed the case differently. “Anna is not anemic,” she said; “but she is iron-deficient.”
Why was that important?
The take away:
1. Iron deficiency is common but sometimes overlooked
2. Iron deficiency can lead to anemia
3. Iron deficiency is very treatable
4. It may take only six weeks for the anemia due to iron deficiency to resolve–but up to six months for iron stores to replenish (i.e., for the iron deficiency itself to resolve).
5. Experts recommend treating for six weeks after laboratory tests (MCV and ferritin) normalize
6. Studies show that taking oral iron supplements every other day is better tolerated and better absorbed
7. Watch out for medication interactions with iron: ask your doctor to check all of your medications to see if they interact–and adjust the timing of the medications and/or dose if they do.
8. Iron should not be taken to “prevent” iron deficiency
Iron Deficiency: Underdiagnosed and often Undertreated
Iron deficiency, in fact, was written all over Anna’s laboratory tests; her MCV and ferritin were in the basement–and in fact both tests had been low for years. Many years. Her symptoms reflected her low iron reserves. She was fatigued, she got short of breath when climbing flights of stairs, and she noticed that she had a funny craving for ice. She was also getting painful sores at the corners of her mouth–something known as “angular cheilitis.”
According to hematologist Dr. Michael Auerbach, “Iron deficiency is often present without anemia, but may result in symptoms of fatigue, decreased exercise tolerance, pagophagia (ice craving), or other forms of pica, and restless leg syndrome.”
Iron is key to both our physical and cognitive well-being. Hemoglobin is a binding site for oxygen and is also important to many of the enzymes required for our cells to be happy.
“Therefore iron deficiency at all levels – iron deficiency without anemia and iron deficiency anemia – should be treated,” according to Dr. German Clenin.
Case Study
Why had Anna suffered from iron deficiency anemia on and off again for years? It turns out that if the underlying iron deficiency isn’t adequately treated, the anemia may recur.
The Basics–Iron Deficiency 101
What is iron-deficiency anemia? What is thought to cause it and what are the symptoms?
Iron deficiency anemia is by far the most common blood disorder: iron deficiency is “estimated to affect more than 35% of the world’s population and more than 50% of pregnant women, translating to a prevalence of more than two billion people worldwide” according to this Lancet article.
Diagnosing this disorder is not difficult but it does require a methodical evaluation.
Your doctor will start by thinking about the timing of your anemia: did it come on suddenly? Gradually over time? Is it just your red blood cells that are low, or other cells (white blood cells, platelets?).
And most importantly, what size are the red blood cells? Anemias are classically categorized according to the size of the red blood cells. Iron deficiency anemia falls into the category of what is known as “microcytic” anemia, where the red cells, as measured by the MCV, or mean corpuscular volume, are small.
Laboratory testing
The laboratory tests that help identify iron deficiency are the hemoglobin (Hgb), MCV and ferritin. The only caveats to this are that ferritin can be increased during infection and other diseases; so if there is suspicion for this, a c-reactive protein (CRP) should be checked to see if there is inflammation.
The blood tests that your doctor will check to see if there is anemia and/or iron deficiency include a CBC or complete blood count, which includes hemoglobin (low in iron deficiency anemia); MCV (low); TIBC or total iron binding capacity, which is usually high in this condition; and a ferritin, which is generally low. A bone marrow biopsy is not necessary to diagnose iron deficiency anemia, but if one is done, absent iron stores will be seen.
Conditions that can look like iron deficiency anemia
In addition to iron deficiency, there are other causes of microcytic anemia and these should be considered: lead toxicity (a cause of anemia both in children and adults and one that was widely observed in Flint, Michigan during the lead poisoning crisis there); thalassemia, which is a genetic trait in the population that causes red blood cells to be small; copper or zinc deficiency; myelodysplastic disease or drug induced anemia; and anemia of chronic disease.
Symptoms
The symptoms of iron deficiency correlate with the degree of anemia. These include fatigue, shortness of breath, headaches, rapid heart rate, restless leg syndrome, a smooth tongue, painful sores at the side of the mouth (cheilosis), and pica (craving unusual non-foods: dirt, ice, starch), which is usually seen when the iron deficiency is severe.
Causes of iron deficiency anemia
It is essential to ask why the iron deficiency anemia is occurring i.e. to identify the existence of predisposing conditions.
Most people get enough iron in the diet. We don’t need all that much–between 5-10mg/day–to maintain our iron stores. That said, heme iron (from meat) is better absorbed and more “bioavailable” than non-heme iron (from legumes).
So why do people develop iron deficiency anemia? The chief reasons are decreased absorption and blood loss.
Decreased Absorption
The main causes of decreased absorption include gastric achlorhydria (a condition where the stomach produces insufficient hydrochloric acid, resulting in reduced iron absorption); infection with H. pylori; celiac disease; and gastric bypass. Anna turned out to have celiac disease; she had likely been malabsorbing iron (and other essential vitamins, including vitamin D and vitamin B-12) for many years.
Blood loss
Another cause of iron deficiency is blood loss: in women, the most common cause is menstruation and pregnancy / childbirth. Unusual causes include being a blood donor and pulmonary hemosiderosis, a rare lung condition. Iron deficiency in a man or post-menopausal woman requires an evaluation of the gastrointestinal (GI) tract to make sure the patient does not have a cancer that is leading to GI blood loss.
Treatment
When your doctor says–”take some iron”–what does that mean? How long should you take it and is there a special way you should take it?
Often doctors will tell patients to “eat more red meat” or give them a list of iron containing foods. But it is actually quite difficult to replace iron by diet alone once you have iron deficiency anemia.
For this reason, most doctors will suggest oral supplementation with iron first since that approach is low cost and oral iron is more easily administered than intravenous iron. The drawbacks are that oral iron can be hard on the stomach, and therefore may be hard to stick with; and absorption can be a challenge. Ferrous gluconate is thought to be the best tolerated, but other formulations include ferrous sulfate, ferrous polysaccharide and ferrous fumarate.
How much to give? Your doctor can calculate the total amount needed to correct the iron deficiency.
Interestingly, every other day dosing seems to increase absorption, according to recent studies; it is also better tolerated, so patients are more likely to take it. A win-win.
How long to treat?
Here is another key take-away: it takes approximately 6-8 weeks to treat the anemia; but it may take up to six months to re-establish iron stores.
According to Dr. Lisa Weissman, Chief of Hematology at Mt. Auburn Hospital, it is necessary to continue to treat for 6 weeks AFTER the MCV blood test is normal, or the ferritin is over 50. This recommendation, she says, is based on her extensive experience of treating iron deficiency. DO NOT stop therapy for a normal hemoglobin, she advises. This happens more frequently than you might think–and almost happened in Anna’s case.
What if oral replacement doesn’t work? There are IV formulations that can be used in patients who don’t tolerate the oral supplements, have chronic blood loss or poor absorption. But “only in exceptional cases will an intravenous injection be necessary (such as a disease needing urgent treatment, or repeated failure of first-step therapy),” according to this review.
The newer IV formulations are safer than those used in the past. What formulation your doctor chooses will depend on the cost and pharmacy availability.
Other medications interact big time with iron
What should patients watch out for when taking iron? Patients need to know that there may be important interactions between iron and a LOT of other medications–a big one is thyroid hormone–so it is key to let your doctor know what other medications you are taking. I have had several young women request advocacy around worsening of their hypothyroidism, with sky high TSH levels — and it turned out that they were taking iron and had not been warned about the interaction. Ways to minimize this interaction include taking the iron at different times from other medications and/or adjusting dosages if necessary.
Warning: don’t take iron as a “prevention”
Other important stuff to be aware of: always take iron under the supervision of a physician. The old Popeye cartoons showing Popeye scarfing down spinach because the iron in it would make him strong—that message is very misleading. Iron is not benign. It is easy to get too much, and too much iron has its own set of problems and can be harmful. “Overloading the body with iron can be dangerous because excess iron accumulation can damage your liver and cause other complications,” according to the Mayo Clinic. This is truly an example of the golden rule–just the right amount, not too much, not too little.
Missing the forest for the trees?
Clinicians do not always recognize when a patient is suffering from iron deficiency, and if they do recognize it, do not always offer sufficient guidance regarding treatment. I honestly don’t know why this easily treated medical syndrome is sometimes overlooked; but I do know that it can be easily missed and that patients are often left a bit on their own to figure out how to treat it.
This is unfortunate because treating iron deficiency is not complicated. But it does require a methodical evaluation, taking the medication correctly, and following up with laboratory studies to make sure that the iron deficiency and/or anemia have been adequately treated.
How do patients feel after replacement? Studies show that people have better exercise tolerance, are overall much less tired, and feel (and think!) much better: studies show improved memory, learning , attention and concentration in both women and children treated for iron deficiency.
The takeaway
One of my mentors, Dr. Dennis Maki, former head of the Infectious Diseases section at UW-Madison, once told me, when I asked what was the most important test to check every year at an annual physical: “The complete blood count,” he said.
“And review it yourself,” he added.
The rewards of diagnosing and treating iron deficiency–more energy, higher concentration, better memory—definitely make reviewing your own lab tests worth the effort!
Resources
Auerbach,M.Treatment of iron deficiency anemia in adults; UpToDate
Clenin, G. The treatment of iron deficiency without anaemia (in otherwise healthy persons). Swiss Medical Weekly
Medical Disclaimer:
All patient names are changed to protect patient confidentiality.
The suggestions given here are not intended as a substitute for the medical advice of your physician. The reader should regularly consult a physician in matters relating to his/her health and particularly with respect to any symptoms that may require diagnosis or medical attention. For additional questions, please call your healthcare provider for reliable, up-to-date information on testing and symptom management of all medical concerns.
Photo credit: thanks to Trevor Pye, Unsplash.com
