Low iron and cancer

Anemia is a fatigue-inducing condition that can be caused by many things, including low levels of iron or the vitamin B12, malaria, or even lead poisoning. But in the context of a diagnosis of cancer, anemia can be caused by the cancer itself, chemotherapy treatments, or both.

The bone marrow is the factory responsible for producing all blood cells, says Allison F. O’Neill, MD, Director of the Pediatric Liver Tumor Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Red blood cells carry oxygen to and from the organs in the body; in the case of anemia, there are too few of these red blood cells. Anemia can be caused by loss of red blood cells (i.e. bleeding), destruction of red blood cells, or the inability to produce red blood cells. Symptoms associated with anemia include dizziness, fatigue, chest pain, shortness of breath or a racing heart.

Here, O’Neill and David P. Steensma, MD, a hematologic oncologist at Dana-Farber, explain the connection between anemia and cancer.

Contents

What cancers are associated with anemia?

Red blood cells.

Cancers that involve the marrow space, such as leukemia or lymphoma, compete with the marrow’s function and interfere with normal red blood cell production. This, then, causes anemia, O’Neill says.

That’s also why cancers, like breast and prostate cancer, can metastasize to the bone marrow, which may also cause anemia, according to Steensma.

But bone marrow doesn’t necessarily need to be involved for anemia to be present in patients. Cancers of the gastrointestinal (GI) system, like colon and stomach cancers, can lead to anemia because of frequent bleeding often associated with those types of cancer.

If you detect anemia in a person over age 50 and there’s no other easy way to explain it, that could be a sign of cancer in the gastrointestinal system.

Occasionally, rapidly growing cancers can also bleed into the center of a tumor. “This might be the cause of an acute drop in blood levels, and an acute cause of anemia,” O’Neill says.

Do cancer treatments lead to anemia?

Often, yes. Chemotherapy agents “target rapidly dividing cells, which by definition are cancer cells. However, they are non-specific in that they also attack other rapidly dividing cells in the body: hair follicles, the lining of the GI tract, and blood cells,” says O’Neill.

If red blood cell counts get too low, patients can receive blood transfusions, or red blood cell growth factors like Epoetin or Darbepoetin alfa, which are administrated weekly or once every three weeks.

Steensma warns that for cancer-caused anemia, just taking iron pills or eating more red meat usually won’t help. Except in the case of bleeding, anemia associated with cancer is usually not due to iron deficiency, so trying to increase your iron levels won’t have much effect.

Remember: not everyone with anemia has cancer

Both physicians stress that being anemic does not mean that you have cancer, or that you will develop cancer. “Cancer is way down on the list in terms of anemia’s most common causes,” says Steensma.

It can often show up in menstruating women, particularly athletes. Globally, the most common causes of anemia are malaria, inherited conditions like sickle cell disease or thalassemia, and parasites like hookworm.

“Cancer is commonly associated with anemia, but anemia has many other causes that are not cancer,” says Steensma.

Anemia: Be Aware of This Cancer-Related Risk

Cancer and its treatments can cause a variety of side effects, and one that you might not know about is anemia. But if you develop this condition, treating it can make you feel better almost immediately—and help you get back to effectively fighting your cancer.

The basics of anemia

Anemia happens when you either don’t have enough healthy red blood cells or the cells you have don’t function properly.

Red blood cells carry hemoglobin, an iron-rich protein that transports oxygen around your body.

Anemia may start slowly. So you might not notice symptoms at first. But as your hemoglobin levels drop, you may experience one or more of these signs and symptoms:

  • Fast or irregular heartbeat
  • Shortness of breath
  • Dizziness
  • Headache or pounding in the ears
  • Chest pain
  • Swelling of hands or feet, or both
  • Pale skin, nail beds, mouth and gums
  • Extreme tiredness

Even with a variety of possible symptoms, identifying anemia can be tricky. And people who have cancer are often fatigued from the disease and its treatment. When in doubt, blood, fecal, or bone marrow tests can determine if you have anemia and help pinpoint what’s causing it.

Why you might become anemic

People with cancer are vulnerable to anemia for many reasons, said Rashmi Khanal, MD, a hematologist-oncologist at Fox Chase Cancer Center.

Cancer itself can cause bleeding that leads to anemia.

Cancer treatments can also bring on anemia. “Most chemotherapy can contribute to it,” Khanal said.

Nutrition plays an essential role. According to Khanal, tumors secrete cytokines leading to cancer related anorexia, which may contribute to nutritional deficiency and anemia henceforth.

Also, the body does not utilize iron, folate, and vitamin B12 when contending with cancer.

“And that can lead to deficiencies that make cancer patients more susceptible to anemia,” Khanal said. Examples of these deficiencies:

  • Cancer, especially GI cancers, can hinder the body absorbing nutrients from food
  • Cancer can infiltrate bone marrow – the blood cell factory – which can lead to a decrease in the production of red blood cells.
  • Cancer sometimes triggers an autoimmune response that destroys the body’s normal red blood cells.

Effective treatments can make a difference

Once doctors have determined what’s causing someone to be anemic, the next step is to treat that underlying cause and to bring the patient’s hemoglobin level up enough that symptoms get better.

Among the possible treatments for anemia:

  • Focusing on calorie rich diet by eating more iron-rich foods, such as dark green leafy vegetables, sweet potatoes, prunes and raisins, beans, meat, and fish. Consulting a nutritionist, like the ones at Fox Chase while receiving cancer treatment, can be helpful.
  • Getting a red blood cell transfusion. “Transfusion is a quick and easy fix, as long as your treatment team simultaneously look for the root cause of the anemia and continues to work on more comprehensive treatment plan of that cause,” Khanal said.
  • Taking oral or parenteral iron, vitamin B12 and/or folic acid supplements when needed.
  • Erythropoietin stimulating agents are available as an option as well.

“Understanding the existence of anemia while patients are receiving cancer treatment is of utmost importance. A simple intervention can change how a person feels, and can make a big difference in a patient’s quality of life,” Khanal said.

Because treatment can significantly improve your day-to-day life, be sure to tell your cancer care team if you have symptoms of anemia.

Anemia experts

The hematology team at Fox Chase also treat people with anemia who don’t have cancer.

“Bone marrow disease, anemia due to chronic kidney disease, and inflammatory diseases— such as lupus and rheumatoid arthritis—can all trigger anemia as well, as can certain medicines,” Khanal said.

Learn more about hematology-oncology treatments at Fox Chase.

What every physician needs to know about iron deficiency:

Iron deficiency is a decrease in total body iron that can be considered to have three successive stages of severity. On average, an iron-replete adult has storage iron reserves that correspond to the amount of iron in a single unit of red blood cells (about 200 to 250mg) in a woman and to the amount of iron in three to four units in a man (about 750 to 1,000mg).

This storage iron is mobilized when iron requirements exceed iron supply. Storage iron depletion describes a decrease in storage iron without effects on hemoglobin or on functional iron compounds in other tissues. An additional decrease in body iron produces iron deficiency without anemia, the stage where lack of iron limits the production of hemoglobin and other iron-requiring metabolites, but before the standards used to distinguish normal from anemic states detect the effect on red-cell production. Finally, further decreases in body iron produce frank iron-deficiency anemia.

Iron deficiency is the most common cause of anemia in the United States and worldwide. Anemia is often the first sign of iron deficiency, but is neither a sensitive or specific indicator, especially in patients with coexisting infectious, inflammatory, or malignant disorders and in those treated with erythropoiesis stimulating agents. Additional laboratory studies are almost always required to establish the diagnosis of iron deficiency.

In the evaluation of patients with iron deficiency, the most important tasks are to identify and to treat the underlying cause of the decrease in body iron. In the majority of patients, the history, physical examination, screening laboratory studies, and review of the peripheral blood smear will suggest the basis for the decrease in body iron.

In men and post-menopausal women, pathological blood loss is by far the most common cause of iron deficiency. In women of child-bearing age, menstrual blood loss adds to iron requirements and each pregnancy occasions iron donation to the fetus. In committed blood donors, iron losses with repeated donation may produce iron deficiency. In infants, children, and adolescents, iron deficiency develops when iron requirements for growth surpass the supply from stores and diet. Iron deficiency is infrequently caused by impaired absorption of iron alone and is rarely the result of genetic disorders.

Correction of iron deficiency is seldom urgent and almost always best begun after the underlying cause has been identified. Iron should be administered only with great caution in the presence of active infection or inflammation, and preferably after their resolution. Oral iron remains the preferred treatment with parenteral preparations reserved for special subsets of patients.

What features of the presentation will guide me toward possible causes and next treatment steps:

The presentation of patients with iron deficiency may have no signs or symptoms or may have features common to all anemias, such as pallor, palpitations, tinnitus, headache, irritability, weakness, dizziness, easy fatigability, and other vague and nonspecific complaints. Both the degree and rate of development of iron deficiency anemia influence the presentation. Because iron deficiency often develops slowly, circulatory and respiratory adaptations may minimize the signs and symptoms, occasionally with remarkable tolerance of severe anemia. Nonetheless, severe iron deficiency anemia can produce cardiorespiratory failure and may need urgent management.

Manifestations of the underlying cause of iron deficiency, such as a source of blood loss, may be evident and help guide further evaluation.

Uncommonly, signs and symptoms thought to be relatively specific for iron deficiency, such as pagophagia, koilonychia, and blue sclerae are present.

Iron deficiency may also produce signs and symptoms independent of anemia, especially in epithelial tissues that have a high iron requirement because of rapid turnover. Glossitis, angular stomatitis, postcricoid esophageal web or stricture (which may become malignant), and gastric atrophy may develop. The combination of glossitis, a sore or burning mouth, dysphagia, and iron deficiency is called the Plummer-Vinson or Paterson-Kelly syndrome.

Other non-hematologic manifestations of iron deficiency include diminished immunity and resistance to infection, decreased physical endurance and work capacity, and impairments in attention, concentration, and other cognitive functions, along with a variety of behavioral and neuropsychological abnormalities, especially in infants and children.

What laboratory studies should you order to diagnosis iron deficiency and how should you interpret the results?

Uncomplicated iron deficiency produces a characteristic sequence of changes in readily available laboratory studies. After iron stores are exhausted, the plasma iron level falls, the total iron-binding capacity (a measure of the plasma transferrin concentration) rises, and the transferrin saturation (the ratio of the plasma iron to total iron-binding capacity) decreases to less than 16%. The supply of iron to developing erythroid cells becomes insufficient, resulting in iron-restricted erythropoiesis.

With reduction of the amount of iron available for heme synthesis, the erythrocyte zinc protoporphyrin level progressively increases. The reticulocyte hemoglobin content (CHr, measured by some automated hematology analyzers) decreases, and the reticulocyte count falls. In the peripheral blood smear, experienced observers can detect the appearance of hypochromic, microcytic erythrocytes whose proportion increases with the duration and severity of iron-restricted erythropoiesis. Automated hematology analyzers detect decreases in the mean corpuscular volume and, in some instruments, increases in the proportion of hypochromic cells. Eventually, the hemoglobin concentration and hematocrit fall.

The rate and degree of change in erythrocyte morphology and red cell indices is governed by the time needed to replace the normal population of normocytic, normochromic cells, and the degree of disparity between erythroid iron requirements and iron supply.

None of these laboratory measures is diagnostic of iron deficiency. The characteristic sequence of laboratory changes in iron-restricted erythropoiesis can result not only from iron deficiency but also from many other disorders that impair iron delivery to the erythroid marrow. Infectious, inflammatory, malignant and, rarely, genetic disorders can produce hypoferremia and constrain the provision of iron to the developing red cell (see below). Moreover, many of the conditions producing iron-restricted erythropoiesis also can coexist with iron deficiency.

Two further laboratory studies may provide more specific diagnostic information. To detect the absence of storage iron, the defining feature of iron deficiency, measurement of the serum (or plasma) ferritin may be helpful. Ferritin is the principal storage protein for intracellular iron but small amounts of ferritin are also secreted into plasma. Although the function is still uncertain, the amount of ferritin synthesized and secreted into the plasma seems to be proportional to the magnitude of body iron stores. Plasma ferritin concentrations decline with storage iron depletion.

Diagnostic interpretation of serum ferritin concentrations is often complicated by conditions that increase serum ferritin independently of body iron stores. Serum ferritin is an acute-phase reactant that is increased in infectious, inflammatory, and malignant disorders. Liver disease may also release tissue ferritins from damaged hepatocytes. Thus, while a low serum ferritin (less than 12 microg/L) is virtually diagnostic of absent iron stores, a serum ferritin within, or above, the reference range does not exclude iron deficiency.

For evidence of tissue iron deficiency, measurement of the serum transferrin receptor concentration may be helpful. The soluble transferrin receptor is a truncated form of the tissue transferrin receptor. Normally, about 80% of plasma transferrin receptors are derived from the erythroid marrow, and their concentration is determined primarily by erythroid marrow activity. Decreased levels of circulating soluble transferrin receptor are found in patients with erythroid hypoplasia (aplastic anemia, chronic renal failure), while increased levels are present in patients with erythroid hyperplasia (thalassemia major, sickle cell anemia, anemia with ineffective erythropoiesis, chronic hemolytic anemia). Iron deficiency increases soluble transferrin receptor concentrations. The plasma transferrin receptor concentration reflects the total body mass of tissue receptor; thus, in the absence of other conditions causing erythroid hyperplasia, an increase in plasma transferrin receptor concentration provides a sensitive, quantitative measure of tissue iron deficiency.

In particular, measurement of plasma transferrin receptor concentration may help differentiate between the anemia of iron deficiency and the anemia associated with chronic inflammatory disorders. Although the plasma ferritin concentration may be disproportionately elevated in relation to iron stores in patients with inflammation or liver disease, the plasma transferrin receptor concentration seems to be less affected by these disorders.

The serum transferrin receptor/serum ferritin ratio seems to improve the identification of iron deficiency in the presence of chronic infection or inflammation and, at present, provides the best available means for noninvasive diagnosis of iron deficiency. Nonetheless, at present no single noninvasive laboratory measurement or combination of measurements can provide a certain diagnosis of iron deficiency in all circumstances. If uncertainty remains, bone marrow examination can be definitive (see below).

In some clinical circumstances, a therapeutic trial of iron is an alternative means of confirming the diagnosis of iron deficiency. Unequivocal proof that iron deficiency is the cause of an anemia can be provided by a specific characteristic response to, and exclusively to, treatment with iron. The definitive diagnostic response consists of both of the following:

  • A reticulocytosis, starting about 3 to 5 days after adequate iron therapy is begun, attaining a maximum on days 8 to 10, and then gradually declining

  • An increase in hemoglobin concentration, beginning just after the maximum reticulocytosis, and no later than 3 weeks after iron therapy is begun, and then persisting until the hemoglobin concentration is returned to normal.

A number of confounding factors may complicate interpretation of the results of a therapeutic trial of iron, including poor compliance with iron therapy, malabsorption of therapeutic iron, continuing blood loss, and the effects of coexisting conditions, especially infectious, inflammatory, or malignant disorders. Despite a positive result with therapeutic iron, the underlying cause of the iron deficiency must be determined.

What conditions can underlie iron deficiency?

In uncomplicated iron deficiency, the characteristic sequence of changes in laboratory studies summarized above is virtually pathognomonic. By contrast, coexisting disorders can produce changes in iron-related measurements that both mimic and obscure those resulting from iron deficiency. Infection, inflammation, malignancy, renal and liver disease principally affect indicators of iron status through their effects on a common pathway that modulates the expression of hepcidin, the chief controller of body iron supply and storage.

With iron deficiency, hepcidin synthesis is suppressed. Plasma iron levels fall because the amounts of iron available from macrophage recycling of senescent erythrocytes, from intestinal absorption, and from mobilization of storage iron in hepatocytes are unable to meet the demands for red cell production, resulting in iron-restricted erythropoiesis. By contrast, infection, inflammation, liver disease, and malignancy typically stimulate hepcidin production via cytokine-mediated pathways. Plasma iron levels fall and iron-restricted erythropoiesis develops because release of iron from macrophages, enterocytes, and hepatocytes is impeded, increasing the amounts of iron in stores.

Consequently, infectious, inflammatory, and malignant disorders can produce changes in the plasma iron, transferrin saturation, erythrocyte zinc protoporphyrin, reticulocyte hemoglobin content, the proportions of hypochromic, microcytic erythrocytes, and in hemoglobin and hematocrit that resemble those resulting from iron deficiency.

Serum ferritin concentrations are decreased with uncomplicated iron deficiency, but increased with infection, inflammation, and malignancy. When occurring together, the effect of infection, inflammation, and malignancy on increasing serum ferritin often predominates over the decrease with lack of iron, concealing the presence of iron deficiency. By contrast, the increase in serum transferrin receptor with iron deficiency is less affected by infection, inflammation, and malignancy. Thalassemia trait can also produce microcytosis, but has little effect on other indicators of iron status.

In patients treated with erythropoiesis stimulating agents for the anemia of chronic renal disease or other disorders, the increased iron requirements of the erythroid marrow can not be met by iron mobilization from replete stores, resulting in iron-restricted erythropoiesis. This state, sometimes labeled “functional iron deficiency” despite the presence of storage iron, is a form of iron-restricted erythropoiesis resulting from stimulated erythropoietic demand for iron.

Uncommonly, a similar pattern can result from endogenous increases in erythropoietin owing to anemia, hypoxemia, and other conditions. Laboratory evaluation shows the pattern of iron-restricted erythropoiesis with a serum ferritin in the reference range, or elevated, and an increased serum transferrin receptor concentration. The CHr may be the earliest indicator that stimulated erythropoietic demand for iron exceeds the available supply.

Rarely, laboratory indicators of iron status are altered by a variety of inherited disorders of iron metabolism. The need for further consideration of a genetic basis for iron deficiency is suggested by a lifelong history of abnormal iron studies coupled with anemia refractory to iron therapy.

When do you need to get more aggressive tests:

If uncertainty about the diagnosis of iron deficiency remains after careful laboratory assessment of the indicators of iron status, bone marrow examination can be definitive. Bone marrow aspiration and biopsy provides information about all of the following:

  • Macrophage storage iron, by semiquantitative grading of marrow hemosiderin stained with Prussian Blue or, if needed, by chemical measurement of nonheme iron

  • Iron supply to erythroid precursors, by determining the proportion and morphology of marrow sideroblasts (that is, normoblasts with visible aggregates of iron in the cytoplasm)

  • General morphologic features of hematopoiesis. If iron deficiency is present, iron stores are absent; if the anemia of chronic disease alone is responsible, iron stores are present and typically increased.

What imaging studies (if any) will be helpful?

No imaging studies are indicated for the diagnosis of iron deficiency, although they may be useful in establishing the underlying cause for the lack of iron.

What therapies should you initiate immediately and under what circumstances – even if root cause is unidentified?

Rarely, severe iron deficiency anemia may need immediate red cell transfusion to prevent cardiac or cerebral ischemia. Red cell transfusion may also be required to support patients whose chronic rate of iron loss exceeds the rate of replacement possible with parenteral therapy.

In patients with heart failure and iron deficiency, clinical trials have provided evidence that treatment with intravenous iron improves outcomes.

What therapy is indicated for iron deficiency?

Generally, iron therapy for iron deficiency can be deferred until the underlying cause for the lack of iron has been identified. If coexistent infection or inflammation is present, iron should be withheld until these disorders are resolved or well controlled.

For most patients, oral iron is the treatment of choice because of its effectiveness, safety, and, economy. Oral iron therapy should begin with a ferrous iron salt, taken separately from meals in three or four divided doses and supplying a daily total of 150 to 200mg of elemental iron in adults or 3mg of iron per kilogram of body weight in children. Simple ferrous preparations are the best absorbed and least expensive. Ferrous sulfate is the most widely used, either as tablets containing 60 to 70mg of iron for adults or as a liquid preparation for children.

Administration between meals maximizes absorption. In patients with a hemoglobin concentration less than 10g/dL, this regimen initially will provide approximately 40 to 60mg of iron daily for erythropoiesis, permitting red cell production to increase to two to four times normal and the hemoglobin concentration to rise by approximately 0.2g/dL/day. An increase in the hemoglobin concentration of at least 2g/dL after 3 weeks of therapy generally is used as the criterion for an adequate therapeutic response.

For milder anemia, a single daily dose of approximately 60mg of iron per day may be adequate. After the anemia has been fully corrected, oral iron should be continued to replace storage iron, either empirically for an additional 4 to 6 months, or until the plasma ferritin concentration exceeds approximately 50microg/L. Most patients are able to tolerate oral iron therapy without difficulty, but 10 to 20% may have symptoms that are attributable to iron. The most common side effects are gastrointestinal and can usually be managed by administering iron with food and decreasing the dose. These measures will diminish the amount of iron absorbed daily, and thereby prolong the period of treatment, but haste in the correction of iron deficiency is rarely needed.

Parenteral iron therapy, despite the reductions in the risk of adverse reactions with newer preparations, should be reserved for the exceptional patient who either remains intolerant of oral iron despite repeated modifications in dosage regimen, malabsorbs iron, or has iron needs that cannot be met by oral therapy because of either chronic uncontrollable bleeding or other sources of blood loss, such as hemodialysis, or a coexisting chronic inflammatory state, such as inflammatory bowel disease. For renal dialysis patients who are managed with erythropoiesis stimulating agents, intravenous iron therapy is recommended.

What other therapies are helpful for reducing complications?

N/A

What should you tell the patient and the family about prognosis?

The patient and family should be told that the prognosis for iron deficiency itself is excellent, and that an excellent response to either oral or parenteral iron can be expected. The overall prognosis is determined by the underlying cause of the iron deficiency.

Both a subjective and a clinical response to treatment can be expected in the first few days after treatment is begun. An enhanced sense of well being may precede the hematologic response. In the absence of complicating factors, reticulocytosis is expected within 3 to 5 days, reaches a peak by days 8 to 10, and then gradually decreases. An increase in hemoglobin follows the reticulocytosis and should be within the reference range by 6 weeks.

“What if” scenarios.

If the expected full response to iron therapy does not occur, then a complete re-evaluation of the patient should be undertaken. Most often, the difficulty is the result of an error in diagnosis, with the anemia resulting from iron-restricted erythropoiesis due to infection, inflammation, or malignancy being mistaken for iron deficiency anemia. Ongoing occult blood loss may cause an incomplete response. Other nutritional deficiencies, hepatic or renal disease, or infectious, inflammatory, or malignant disorders may delay recovery. A genetic basis for iron deficiency should be considered if these possibilities can be excluded and the anemia is does not respond fully to parenteral therapy, especially in the presence of a lifelong history.

If the expected full response is not obtained with oral iron therapy, the adequacy of the form and dose of iron used should be reconsidered, compliance with the treatment regimen reviewed, and, finally, the possibility of malabsorption considered. A screening test for iron malabsorption is the administration to the fasting patient of 100mg of elemental iron as ferrous sulfate in a liquid preparation, followed by measurements of plasma iron concentrations 1 and then 2 hours later.

In an iron-deficient patient with an initial plasma iron concentration less than 50mg/dL, an increase in plasma iron concentration of 200 to 300mg/dL is expected. An increase in plasma iron concentration less than 100mg/dL suggests malabsorption, and may be an indication for a small-bowel biopsy.

Pathophysiology

Iron deficiency results from a sustained increase in iron requirements over iron supply. The iron requirement is the sum of physiologic needs (for the small daily losses in body cells and fluids, for losses during menstruation and pregnancy in women, and for growth in infants, children and adolescents) and any additional amounts for replacement of pathological losses (most often, some form of blood loss). In normal men, the daily basal iron loss is slightly less than 1.0mg/day. In healthy menstruating women, the daily basal iron loss is approximately 1.5mg/day. In iron balance, these physiologic losses are matched with the iron supply derived from controlled absorption of corresponding amounts of iron from the diet.

Iron balance is maintained by hepcidin, the chief controller of body iron supply and storage, through interaction with ferroportin, a transmembrane protein that is the only known cellular iron exporter in humans. Hepcidin binds to ferroportin, inducing its internalization and degradation, thereby inhibiting iron efflux from the principal sources of plasma iron: macrophages, duodenal enterocytes, and hepatocytes.

Under physiologic conditions, hepatic hepcidin production is the mechanism whereby body iron supply is coordinated with iron need. If body iron stores expand, hepcidin production increases. Increments in plasma hepcidin reduce the amount of ferroportin in cell membranes, causing a prompt fall in plasma iron concentration by decreasing macrophage release of iron derived from senescent red blood cells, diminishing delivery of iron from enterocytes absorbing dietary iron, and inhibiting release of iron stored in hepatocytes. Conversely, if body iron stores contract, hepcidin production decreases. Decrements in plasma hepcidin concentration increase the amount of ferroportin, producing a rise in plasma iron concentration as a consequence of enhanced delivery from macrophages, increased dietary iron absorption from enterocytes, and mobilization of storage iron from hepatocytes.

In addition to these effects of body iron stores, hepcidin production is stimulated by inflammation and inhibited by increased erythropoiesis. Depending on clinical circumstances, the effects of inflammation or increased erythropoiesis on hepatic hepcidin synthesis may predominate over the effects of body iron stores.

The most common pathologic cause of increased iron requirements leading to iron deficiency is blood loss, usually gastrointestinal in origin from any hemorrhagic lesion, including malignancy, ulcer, gastritis, drug-induced lesions (alcohol, salicylates, steroids, and nonsteroidal antiinflammatory agents) and parasitic infections (hookworm infection, Schistosoma mansoni, Schistosoma japonicum, and severe Trichuris trichiura). Less commonly, genitourinary blood loss (including chronic hemoglobinuria and hemosiderinuria resulting from paroxysmal nocturnal hemoglobinuria or from chronic intravascular hemolysis) can be responsible. Repeated blood donation also may lead to iron deficiency. In infants, children, and adolescents, the need for iron for growth may exceed the supply available from diet and stores.

Impaired absorption of iron in itself can restrict iron supply but is uncommonly the sole source of iron deficiency. Nonetheless, in those patients in whom gastrointestinal evaluation fails to identify a source of blood loss, as well as in those unresponsive to oral iron therapy, coeliac disease, autoimmune, atrophic, or Helicobacter pylorigastritis may be responsible.

What other clinical manifestations may help me to diagnose iron deficiency?

A relatively specific symptom of iron deficiency is pagophagia, a variant of pica characterized by the obsessive consumption of ice. The clinical history also should elicit symptoms associated with disorders that have a high prevalence of iron deficiency, including heart failure, pulmonary arterial hypertension, and restless legs syndrome (Ekbom syndrome), a neurologic disorder characterized by a distressing need or urge to move the legs (akathisia). Distinctive physical findings occur in only a small proportion of patients with iron deficiency but include koilonychia (thin, brittle fingernails with the distal half of the nail in a concave or “spoon” shape) and blue sclerae (a bluish hue of the sclerae thought to result from thinning of the sclerae, making the choroid visible). Glossitis and angular stomatitis are other, much less specific, physical manifestations.

What other additional laboratory studies may be ordered?

Gene sequencing is needed for definitive identification of a variety of rare genetic disorders that either cause iron deficiency or simulate some of the laboratory features of iron deficiency, including iron-refractory iron deficiency anemia (mutations in TMPRSS6, encoding matriptase-2), atransferrinemia (mutations in TF, encoding transferrin), aceruloplasminemia (mutations in CP, encoding ceruloplasmin), divalent metal transporter 1 (DMT1) deficiency (mutations in SLC11A2, encoding DMT1 {divalent metal transporter 1]), some forms of ferroportin disease (mutations in SLC40A1, encoding ferroportin), heme oxygenase 1 deficiency (mutations in HMOX1, encoding heme oxygenase 1), and several inherited sideroblastic anemias.

What’s the evidence?

Auerbach, M, Ballard, H. “Clinical use of intravenous iron: administration, efficacy, and safety”. Hematology Am Soc Hematol Educ Program. vol. 2010. 2010. pp. 338-347.

Baker, RD, Greer, FR. “Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age)”. Pediatrics. vol. 126. 2010. pp. 1040-1050.

Camaschella, C, Poggiali, E. “Inherited disorders of iron metabolism”. Curr Opin Pediatr. vol. 23. 2011. pp. 14-20.

Carson, JL, Adamson, JW. “Iron deficiency and heart disease: ironclad evidence?”. Hematology Am Soc Hematol Educ Program. vol. 2010. 2010. pp. 348-350.

Hershko, C, Skikne, B. “Pathogenesis and management of iron deficiency anemia: Emerging role of celiac disease, Helicobacter pylori, and autoimmune gastritis”. Semin Hematol. vol. 46. 2009. pp. 339-350.

Madore, F, White, CT, Foley, RN. “Clinical practice guidelines for assessment and management of iron deficiency”. Kidney Int Suppl. vol. 110. 2008. pp. S7-S11.

Munoz, M, Garcia-Erce, JA, Remacha, AF. “Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis”. J Clin Pathol. vol. 64. 2011. pp. 281-286.

Iron-Deficiency Anemia and Cancer: What’s the Link?

If you have cancer, you may not be familiar with the role that iron deficiency anemia often plays in the disease. This type of anemia is a condition in which the body can’t produce enough hemoglobin, a substance found in red blood cells that carries oxygen, because of inadequate iron. According to a study published in March 2015 in the journal PLOS ONE, people who have iron deficiency anemia have a significantly higher overall cancer risk than those who don’t, and the risk of pancreatic, kidney, liver, and bladder cancers is significantly elevated even up to five years after iron deficiency is diagnosed.

On the flip side, all cancer types are associated with an increased risk of developing iron deficiency anemia, though the risk is higher with certain types of cancer. And the consequences of iron deficiency anemia can be particularly severe in people with cancer, potentially interfering with treatment and lowering the odds of survival.

Here’s what you should know about the detection and treatment of iron deficiency anemia when you have cancer, and how the two conditions are connected.

Causes of Iron Deficiency

According to the American Cancer Society, the main causes of anemia in people with cancer are the cancer itself, blood loss, nutritional deficiencies, major organ problems, and sickle cell disease or thalassemia (inherited disorders in which the body destroys too many red blood cells).

In adults, the most common cause of iron deficiency anemia is blood loss — in either the gastrointestinal (GI) tract or the genitourinary system, according to Lanie K. Francis, MD, a hematologist and medical oncologist at UPMC Hillman Cancer Center in Pittsburgh. People who have cancers of “those regions that present with bleeding,” she says, “are most at risk of iron deficiency anemia.”

In a study published in July 2013 in the Annals of Oncology, iron deficiency was most commonly seen in people with pancreatic cancer (present in 63 percent of participants), followed by colorectal cancer (52 percent) and lung cancer (51 percent). In forms of cancer with solid tumors, later stages of the cancer were associated with a higher risk of iron deficiency. For blood cancers, the prevalence of iron deficiency was similar across all cancer stages.

Chemotherapy and Iron Deficiency

Another factor involved in iron deficiency in people with cancer is chemotherapy. In a study published in 2015 in the journal Blood, 75 percent of people on chemotherapy for various cancer types were found to be iron deficient, with 60 percent showing signs of absolute iron deficiency (see beow). The researchers noted that chemotherapy can cause iron deficiency due to a reduced appetite and poor nutrition, gastrointestinal mucosal damage that results in blood loss, or the release of chemicals known as cytokines.

What’s more, chemotherapy can cause what’s known as pancytopenia, in which many components of blood — including red cells, white cells, and platelets — are low in number.

Common Types of Iron Deficiency in Cancer

Two main forms of iron deficiency are seen in people with cancer: absolute and functional.

In absolute iron deficiency, the body lacks an adequate supply of iron. According to a study published in December 2015 in the Central European Journal of Medicine, absolute iron deficiency is usually caused by blood loss, poor iron absorption, or both. Because of this, colorectal cancer carries an especially high risk of absolute iron deficiency, but other cancers carry risks as well.

In functional iron deficiency, the body has adequate iron stores — mostly in the blood, liver, spleen, and bone marrow — but for various reasons related to biochemistry, it can’t adequately use this iron. Common causes of functional iron deficiency include inflammation — which may be caused by cancer, infection, chronic kidney disease, or other chronic diseases — as well as certain drugs or nutritional deficiencies, such as a copper deficiency.

What It Means to Have Anemia and Cancer

Iron deficiency anemia “may be the red flag that leads a health care provider to search for cancer,” says Francis, since it’s typically caused by blood loss, which often occurs in colon cancer and uterine cancer but is less commonly in bladder cancer.

But no matter its cause, iron deficiency anemia can make the treatment of cancer more difficult. “If a patient has long-standing iron deficiency anemia before the cancer diagnosis,” Francis says, “it can weaken or decondition them, which can make it difficult for them to tolerate chemotherapy or other treatment.”

According to the study in the Central European Journal of Medicine, anemia from any cause is associated with reduced physical fitness and reported quality of life in people with cancer. Anemia is also associated with a higher mortality rate in people with cancer, although the article notes that it’s not clear whether treating anemia improves survival — meaning that it could sometimes be a symptom rather than a cause of worsening health.

Getting Tested and Treated

If you have cancer, it’s especially important to see your doctor and get tested for anemia if you experience symptoms like fatigue, a fast heartbeat, shortness of breath or trouble breathing during physical activity, dizziness, chest pain, swelling in your hands or feet, or paleness of your skin, nail beds, mouth, or gums.

If a blood test confirms that you have iron deficiency anemia, there are two potential (and complementary) courses of action your doctor may take: finding out what’s causing your deficiency, and treating it directly.

To begin with, your doctor will likely perform further tests to determine the cause of your anemia. These tests may include measuring your transferrin saturation (TSAT), which signals functional iron deficiency, as well as your ferritin level, which can indicate absolute iron deficiency. The “gold standard” test for confirming absolute iron deficiency is a bone marrow biopsy, according to Francis — but this is rarely necessary.

If you’re experiencing blood loss due to your cancer or some other established cause, your healthcare team will probably already be trying to stop any active bleeding, Francis says. But if there’s no known source of blood loss, your doctor will most likely ask about symptoms that could indicate blood loss and may test your stool for blood by means of a fecal occult blood test (FOBT), or consider ordering a colonoscopy.

To directly treat your iron deficiency, your doctor may prescribe either oral iron supplements or intravenous (IV) iron. If you have anemia that’s especially severe or sudden, you may also be given a red blood cell transfusion. Since a transfusion raises your hemoglobin level quickly, it can be an important way to ensure that enough oxygen is reaching your vital organs.

In the long term, it’s also important to follow a healthy, iron-rich diet, including foods like meat and fish, dark green leafy vegetables, dried fruits, beans and other legumes, and enriched bread, cereal, and pasta. Meat sources of iron tend to be the best choice when it comes to bioavailability of iron and maximum iron absorption from the diet.

“Treatment of iron deficiency in cancer patients is no different than in the noncancer population,” Francis notes. But since the stakes are potentially so much higher when you have cancer, if you suspect that you may have iron deficiency anemia, don’t hesitate to see your doctor for testing and treatment.

Understanding the Connection Between Anemia and Cancer

Iron-deficiency anemia is caused by a lack of healthy red blood cells in the body. Your body makes red blood cells in bone marrow, a spongy material inside your body’s largest bones.

Red blood cells are important for fighting infections, clotting blood, and carrying oxygen throughout your body. This can happen when your body doesn’t make enough red blood cells, when you’ve had severe bleeding, or when your body starts to destroy its red blood cells.

When red blood cells are damaged or not numerous enough, they cannot carry oxygen efficiently throughout your body. This leads to weakness and fatigue, and can harm your body if left untreated.

Iron-deficiency anemia is most commonly caused by a poor diet, digestive disorders, menstruation, pregnancy, bleeding disorders, and advanced age. Also, it appears there are several types of cancers closely linked to anemia.

Here’s a rundown on how anemia is linked to these cancers:

Anemia and blood cancer

Blood cancer is one type of cancer commonly linked to anemia. That’s because blood cancer affects how your body produces and uses red blood cells.

Most of the time, blood cancers start in the bone marrow and cause abnormal blood cells to start growing. These abnormal blood cells reduce your body’s abilities to work normally. In some cases they may cause serious bleeding and infections.

types of blood cancer

Blood cancers are grouped into three main types:

  • Leukemia. This is cancer in your blood and bone marrow caused by a rapid production of abnormal white blood cells. These blood cells are not good at fighting infections and reduce the ability of the bone marrow to make red blood cells, which can lead to anemia.
  • Lymphoma. This is a type of cancer in the blood affecting the body’s lymphatic system, the system that removes extra fluid from your body and makes immune cells. Lymphoma leads to the production of abnormal blood cells that harm your immune system.
  • Myeloma. This is a type of cancer affecting infection-fighting cells in your body. Abnormal myeloma cells weaken your body’s immune system, making you more prone to infection.

Anemia and bone cancer

Bone cancer is rare in adults. It begins when abnormal cells begin to grow in the bones into masses, or tumors, called sarcoma.

Experts don’t know exactly what causes most cases of bone cancer. However, some bone cancers appear to be linked to genetics, while others are related to previous exposure to radiation, such as radiation therapy for other, previous cancers.

TYPES of bone cancer

The most common types of bone cancer include:

  • Chondrosarcoma. This cancer occurs in cells that produce cartilage, causing tumors around bones.
  • Ewing’s sarcoma. This cancer involves tumors in the soft tissue and nerves surrounding bone.
  • Osteosarcoma. Rare, but the most common type of bone cancer, this cancer causes bones to become weak and easily broken. It more commonly affects teenagers and young adults.

It appears some bone cancers lead to production of abnormal red blood cells, which can lead to anemia.

Anemia and cervical cancer

Cervical cancer is caused by abnormal cell growth in the cervix, the lower part of the uterus that connects to the vagina. The sexually transmitted infection human papillomavirus (HPV) is thought to cause most cases of cervical cancer. Abnormal growth of cells in the cervix often causes bleeding and iron deficiency, which leads to anemia.

Anemia and colon cancer

Colon cancer is caused by abnormal growth of cells in the large intestine (colon). These cells often form tumors on or in blood vessels in the colon that carry red blood cells.

Research suggests that these tumors can cause bleeding and a loss of healthy red blood cells, which commonly causes anemia. Most people with colon cancer experience rectal bleeding and bloody stool, as well as weakness and fatigue linked to their anemia.

Anemia and prostate cancer

Prostate cancer is the abnormal growth of cells in the prostate, a small gland men have to produce and transport semen. Men with prostate cancer sometimes experience bleeding from their prostate, which can appear as blood in their semen.

Research from 2004 suggests that men with prostate cancer also experience abnormalities in their bone marrow, which can affect production of red blood cells. The bleeding and blood cell abnormalities can cause anemia.

Anemia in People With Cancer

What is anemia?

When you don’t have enough healthy red blood cells, you have a condition called anemia. This means your blood has too little hemoglobin (Hgb), the part of the red blood cell (RBC) that carries oxygen to all the cells in your body.

Anemia often starts slowly, so you may not even notice symptoms at first. As your hemoglobin level gets lower you may have one or more of these symptoms:

  • Fast heart beat
  • Shortness of breath
  • Trouble breathing when doing things like walking, climbing stairs, or even talking
  • Dizziness
  • Chest pain
  • Swelling in the hands and/or feet
  • Pale skin, nail beds, mouth, and gums
  • Extreme tiredness (fatigue)

Severe tiredness and weakness are often the symptoms that bother people most.

What causes anemia?

There are many different reasons a person with cancer might have anemia. Some common causes are:

  • The cancer itself
  • Cancer treatment, such as radiation or chemotherapy
  • Blood loss (this can be slow constant bleeding such as from the intestine or bladder; or fast bleeding, like heavy menstruation or bleeding from a stomach ulcer)
  • Missing certain vitamins or minerals in the diet
  • Low iron levels in blood
  • Major organ problems (including severe heart, lung, kidney, or liver disease)
  • Red blood cells (RBCs) being destroyed by the body before they’re replaced
  • Chronic kidney disease
  • The body making fewer RBCs
  • Sickle cell disease or thalassemia (inherited disorders that cause the body to destroy too many red blood cells)
  • A combination of any of these factors

Some risk factors may make a person with cancer more likely to have anemia. These include:

  • Platinum-based chemotherapy (this is a certain group of chemo drugs)
  • Certain tumor types (such as lung or ovary tumors)
  • Having a low hemoglobin level before you had cancer

Tests for what is causing your anemia

A complete blood count (CBC) is a blood test that measures your hemoglobin level and other characteristics of your red blood cells (such as their size). This test not only shows if you have anemia, but it can also help your doctor figure out what might be causing it.

You might also need other tests to help to find what is causing it. These could include:

  • Blood chemistry tests to check organ function and levels of vitamins and minerals
  • A blood test called a reticulocyte count (Reticulocytes are very young red blood cells just released from the bone marrow, so this test shows how many new red cells your body is making.)
  • A bone marrow exam
  • A blood test to look at your iron levels
  • A test of your stool (feces) to check for blood (called a fecal occult blood test or FOBT)

Your doctor or nurse can use the results of these tests, along with your medical information and a physical exam, to get an idea of what might be causing your anemia. Sometimes no cause can be found other than “anemia of chronic disease.” This type of anemia is often found in people with long-lasting problems like congestive heart failure, inflammatory diseases, or cancer.

What problems can anemia cause?

Learning the cause of the anemia is important, but the first thing the doctor needs to know is how “bad” it is.

Anemia can affect your quality of life and has been found to shorten survival in people with cancer. It can make you feel very tired because cells in your body can’t get enough oxygen. In some cases, this lack of oxygen may be bad enough to threaten your life. Anemia can also make your heart work harder. So if you already have a heart problem, anemia can make it worse.

Severe anemia may mean you have to delay your cancer treatment or have your treatment dose reduced. It can also cause some treatments to not work as well as they should.

Your doctor or nurse may try to figure out your risk of serious problems from the anemia based on any symptoms you are having and your hemoglobin level. If you’re not having symptoms, they will try to figure out how likely you are to have them in the near future. This will be based on a number of things, including:

  • Your hemoglobin level and other lab results
  • The type of cancer treatments you’ve had in the past
  • The chances that any treatments you’re now getting could make the anemia worse
  • Your need for blood transfusions in the past 6 months
  • Whether you have lung, heart, or blood vessel (circulation) problems
  • Your age

If you don’t seem to be at risk for problems from anemia, your doctor or nurse will watch your hemoglobin level closely and ask about symptoms each time you visit the office.

How bad is the anemia?

Doctors often rate how severe or how “bad” anemia is based on the amount of hemoglobin in your blood. Even though your symptoms may not match, doctors use this way to rank anemia when deciding about treatment.

    Mild anemia: hemoglobin between 10 and the lower limit of normal for your age, sex, and the lab value
    Moderate anemia: hemoglobin 8 to 10 g/dL
    Severe anemia: hemoglobin 6.5 to 8 g/dL
    Life-threatening anemia: hemoglobin less than 6.5

Some serious symptoms of anemia are:

  • Chest pain
  • Fast heart beat
  • Swelling in your legs
  • Feeling dizzy or lightheaded
  • Having trouble breathing when you exert yourself

If you have any of these symptoms, tell your doctor or nurse right away.

Other medical problems such as heart disease or chronic lung disease may already affect how much oxygen is getting to your body. These conditions along with anemia could increase your risk of serious problems. If your cancer care team finds that your anemia is a serious threat to your health, you may need a blood transfusion.

How is anemia treated?

There are 2 main goals in treating anemia:

  • Treat the cause of the anemia
  • Raise the hemoglobin level so that symptoms get better

Depending on the cause of the anemia, treating it may include things like eating iron-rich foods, medicines, delaying or changing cancer treatment; and stopping any bleeding.

If the hemoglobin level needs to be raised quickly, a transfusion of red blood cells may be given.

Talk to your cancer care team about what treatment is right for you. As with any medical problem, the expected benefits of treatment should always outweigh the possible risks.

Iron-rich foods for anemia

If your anemia is mild, you may be asked to try to eat more iron-rich foods. Foods that contain high amounts of iron include

  • Dark green
  • Leafy vegetables
  • Sweet potatoes
  • Prunes and raisins
  • Dried apricots and peaches
  • Beans
  • Meat and fish
  • Enriched bread, cereal, and pasta

Ask your healthcare provider which foods would be best for you.

The American Red Cross has a detailed list of iron-rich foods on their website, www.redcrossblood.org.

Blood transfusions to treat anemia

A red blood cell transfusion is safe, and a common way to treat anemia in people with cancer. It raises the level of hemoglobin quickly to improve symptoms, help the patient feel better, and make sure that enough oxygen is getting to vital organs.

The need for a blood transfusion depends on how bad your symptoms are and your hemoglobin level. A transfusion is done most often when the hemoglobin level is less than 8 g/dL.

A blood transfusion requires careful matching of donated blood to the recipient’s blood. And while blood transfusions fix the problem very quickly, there is a small chance of serious risks. The most common problem is a transfusion reaction. This happens when the patient’s immune system attacks proteins on the foreign blood cells. This often looks like an allergic reaction. Most of these reactions are minor and can be treated, but sometimes they can be more serious.

Transfusion-related lung injury is one of the more serious risks. It can cause trouble breathing and require treatment in the hospital. Another possible risk is the chance of getting certain germs, such as the hepatitis B virus. But the careful blood testing and screening that’s used today have made the risk of infections very small.

In some people, transfusion-related circulatory overload (TACO) can happen if blood is given too quickly for the heart to handle it. And people who get many blood transfusions (usually more than 25 units of red cells) may end up with too much iron, which would then need to be treated.

Contact us at 1-800-227-2345 or explore www.cancer.org to learn more about blood transfusions.

Drugs to treat anemia

Many different drugs can be used to treat anemia, but this takes longer. In some cases, taking iron, vitamin B12, and/or folic acid supplements can help. There’s also a liquid form of iron that can be put right into your blood (as an IV infusion).

Another way to treat anemia in some patients is to use drugs that tell the body to make more red blood cells. These drugs work like a hormone (called erythropoietin) made by the kidneys to help the body make its own new red blood cells. If one of these drugs is recommended, your healthcare provider will talk to you about the risks and the benefits of the drug. These drugs can cause very serious side effects. Still, they can help patients getting chemotherapy have higher hemoglobin levels and need fewer blood transfusions. This may result in a gradual improvement of anemia-related symptoms.

These drugs are given as shots under the skin, and usually take at least 2 weeks to start working.

If you notice symptoms…

It’s important to watch for anemia and its symptoms throughout your treatment. Tell your cancer care team if you’re having any of the symptoms described here. Be sure to mention how the symptoms affect your day-to-day life. Doing so will help you get the treatment you need when you need it.

3 Ludwig H, Müldür E, Endler G, Hübl W. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol. 2013;24(7):1886-92.

4 Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011;434(3):365-81.

5 Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011-23.

8 Beguin Y, Aapro M, Bokemeyer C, Glaspy J, Hedenus M, Littlewood TJ. Current practice in diagnosis and treatment of chemotherapy-induced anemia in five European countries – a patient record study. Blood. 2010;116:1512.

9 Naoum FA. Doenças que alteram os exames hematológicos. 1st ed. São Paulo: Atheneu; 2010. p. 212.

10 Crawford J, Cella D, Cleeland CS, Cremieux PY, Demetri GD, Sarokhan BJ, et al. Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy. Cancer. 2002;95(4):888-95.

12 Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, et al. American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Blood. 2010;116(20):4045-59.

13 NCCN. Cancer and chemotherapy-induced anemia, Version 2; 2016.

14 Schrijvers D, De Samblanx H, Roila F. Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use. Ann Oncol. 2010;21(Suppl. 5):v244-v247.

16 Toblli JE, Angerosa M. Optimizing iron delivery in the management of anemia: patient considerations and the role of ferric carboxymaltose. Drug Des Dev Ther. 2014;8:2475-91.

18 Gafter-Gvili A, Rozen-Zvi B, Vidal L, Leibovici L, Vansteenkiste J, Gafter U, et al. Intravenous iron supplementation for the treatment of chemotherapy-induced anaemia – systematic review and meta-analysis of randomised controlled trials. Acta Oncol. 2013;52(1):18-29.

19 Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman A, Bahrain H, et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J Clin Oncol. 2004;22(7):1301-7.

20 Auerbach M, Silberstein PT, Webb RT, Averyanova S, Ciuleanu TE, Shao J, et al. Darbepoetin alfa 300 or 500 µg once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. Am J Hematol. 2010;85(9):655-63.

21 Bastit L, Vandebroek A, Altintas S, Gaede B, Pintér T, Suto TS, et al. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol. 2008;26(10):1611-8.

22 Hedenus M, Birgegård G, Näsman P, Ahlberg L, Karlsson T, Lauri B, et al. Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study. Leukemia. 2007;21(4):627-32.

23 Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist. 2007;12(2):231-42.

24 Pedrazzoli P, Farris A, Del Prete S, Del Gaizo F, Ferrari D, Bianchessi C, et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha. J Clin Oncol. 2008;26(10):1619-25.

25 Steensma DP, Sloan JA, Dakhil SR, Dalton R, Kahanic SP, Prager DJ, et al. Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to darbepoetin alfa for patients with chemotherapy-associated anemia. J Clin Oncol. 2011;29(1):97-105.

26 Luporsi E, Mahi L, Morre C, Wernli J, de Pouvourville G, Bugat R. Evaluation of cost savings with ferric carboxymaltose in anemia treatment through its impact on erythropoiesis-stimulating agents and blood transfusion: French healthcare payer perspective. J Med Econ. 2012;15(2):225-32.

27 Steinmetz T, Tschechne B, Harlin O, Klement B, Franzem M, Wamhoff J, et al. Clinical experience with ferric carboxymaltose in the treatment of cancer and chemotherapy-associated anaemia. Ann Oncol. 2013;24(2):475-82.

28 Hedenus M, Karlsson T, Ludwig H, Felder M, Roubert B, Birgegard G. Intravenous ferric carboxymaltose as sole anemia therapy in patients with lymphoid malignancies, chemotherapy-induced anemia and functional iron deficiency. Blood. 2013;122(21):3439.

29 Calvet X, Gené E, ÀngelRuíz M, Figuerola A, Villoria A, Cucala M, et al. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose or oral iron as preoperative treatment in patients with colon cancer and iron deficiency anaemia. Technol Health Care. 2016;24(1):111-20.

30 Calleja JL, Delgado S, Del Val A, Hervás A, Larraona JL, Terán Á, et al. Ferric carboxymaltose reduces transfusions and hospital stay in patients with colon cancer and anemia. Int J Colorectal Dis. 2016;31(3):543-51.

Iron deficiency anaemia

Angiodysplasia

Gastrointestinal bleeding can also be caused by a condition called angiodysplasia. This is the result of abnormal, fragile superficial blood vessels in the gastrointestinal tract, which can cause bleeding.

Chronic kidney disease

People with chronic kidney disease (CKD) often develop iron deficiency anaemia.

Most people with CKD who have iron deficiency anaemia will be given iron supplement injections, although daily tablets may be tried first.

You can read more about treating anaemia in people with CKD on the National Institute for Health and Care Excellence (NICE) website.

Other causes

Other conditions or actions that cause blood loss and may lead to iron deficiency anaemia include:

  • inflammatory bowel disease – a condition that causes redness and swelling (inflammation) in the digestive system, such as Crohn’s disease and ulcerative colitis
  • oesophagitis – inflammation of the gullet (oesophagus) caused by stomach acid leaking through it
  • schistosomiasis – an infection caused by parasites, mainly found in sub-Saharan Africa
  • blood donation – donating a large amount of blood may lead to anaemia
  • trauma – a serious accident, such as a car crash, may cause you to lose a large amount of blood
  • nosebleeds – having regular nosebleeds may lead to anaemia, although this is rare
  • haematuria (blood in your urine) – but this rarely causes anaemia and may be a symptom of another condition

Malabsorption

Malabsorption is when your body can’t absorb iron from food, and is another possible cause of iron deficiency anaemia.

This may happen if you have coeliac disease, a common digestive condition where a person has an adverse reaction to gluten, or surgery to remove all or part of your stomach (gastrectomy).

Lack of iron in your diet

Unless you’re pregnant, it’s rare for iron deficiency anaemia to be caused solely by a lack of iron in your diet.

However, a lack of dietary iron can increase your risk of developing anaemia if you also have any of the conditions mentioned above.

Some studies suggest vegetarians or vegans are more at risk of iron deficiency anaemia because of the lack of meat in their diet.

If you are vegetarian or vegan, it is possible to gain enough iron by eating other types of food, such as:

  • beans
  • nuts
  • dried fruit, such as dried apricots
  • wholegrains, such as brown rice
  • fortified breakfast cereals
  • soybean flour
  • most dark-green leafy vegetables, such as watercress and curly kale

If you’re pregnant, you may need to increase the amount of iron-rich food you consume during pregnancy to help prevent iron deficiency anaemia.

Read more about vegetarian and vegan diets

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  • The role of sugar & iron in cancer

    A lot of studies and natural treatments against cancer involve starving cancer cells of sugar (simple carbohydrates and all sugars except fruit sugar) and iron. Here’s the science behind why you should lower your risk of getting cancer by cutting down on these two.

    Sugar: As long ago as 1982, cancer research proved that sugar was a big culprit. As per the below cancer research, “Cancer cells demonstrate a 3 to 5 fold increase in glucose uptake compared to healthy cells,” said GE Demetrakopoulos, who worked extensively on Cancer Research, and published in the Harvard Catalyst journal vol.42, p.756S, in Feb.1982. Further studies have proven the link between sugar and neoplastic diseases (where there is tumour growth and tumour cells multiply in a sugar happy environment). In fact, people who drink two or more sweetened soft drinks a week (especially with alcohol) have a much higher risk of pancreatic cancer, an unusual but deadly cancer.
    In a study of 60,000 people in Singapore found that sugar was to blame, said Mark Pereira of the University of Minnesota, who led the study.
    “The high levels of sugar in soft drinks may be increasing the level of insulin in the body, which we think contributes to pancreatic cancer cell growth,” Pereira said in a statement.
    Insulin, which helps the body metabolize sugar, is made in the pancreas.

    Writing in the journal Cancer Epidemiology, Biomarkers & Prevention, Pereira and colleagues said they followed 60,524 men and women in the Singapore Chinese Health Study for 14 years.
    Over that time, 140 of the volunteers developed pancreatic cancer. Those who drank two or more soft drinks a week had an 87 percent higher risk of being among those who got pancreatic cancer.
    Pereira said he believed the findings would apply elsewhere.
    Tumor cells use more glucose than other cells.
    One 12-ounce (355 ml) can of non-diet soda contains about 130 calories, almost all of them from sugar.

    Iron: Numerous laboratory and clinical investigations over the past few decades have observed that one of the dangers of iron is its ability to favour neoplastic cell growth. Iron is carcinogenic due to its catalytic effect on the formation of hydroxyl radicals, suppression of the activity of host defence cells and promotion of cancer cell multiplication. In short, people with an abnormally high iron count in their blood create a conducive environment to host and promote cancer or malignant tumour cells. In both animals and humans, primary neoplasms develop at body sites of excessive iron deposits. Quantitative evaluation of body iron and of iron-withholding proteins has prognostic value in cancer patients. Procedures associated with lowering host iron intake and inducing host cell iron efflux can assist in prevention and management of neoplastic diseases, which means withhold cancerous growth. Pharmaceutical methods for depriving neoplastic cells of iron are being developed in experimental and clinical protocols, as per ED Weinberg, from the Department of Biology, Indiana University, Bloomington.

    My advise?
    Cut down simple carbs: White flour, sugar, corn, cold drinks, rice, milk – all contain sugars that will fuel cancer cell growth. Increase fibre intake to flush out sugar deposits in the blood and body, focus on anti inflammatory proteins that help regulate blood sugar (beans, soya milk, tofu, nuts and seeds) and starve any cancerous growth in your body. All of us have some cancer cells. If we feed them with our lifestyle, we are prone to getting cancer.
    Feed the body with anti-cancer foods (foods that kill cancer cells) like broccoli, green tea, garlic, yoghurt, cabbage, tomatoes, apples, papaya, all berries. While cutting down on sugars will inhibit growth, increasing intake of anti cancer foods will kill existing cells.
    Exercise: Working out 30-45 min 4 times a week will ensure your excess sugar in the body gets flushed out. And exercise increases the good cells in your body. When the body’s good cells grow and out number cancer cells, the body’s ability to fight cancer increases.
    Watch your HB count: And yes, haemoglobin should be between 12 – 15 g/dl, higher than that creates a conducive environment for cancer cells growth.

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