Managing Iron Deficiency Anemia in Pharmacy Practice

Transcription

1 Program Name: Managing Iron Deficiency Anemia in Pharmacy Practice Michael Boivin, Bsc. Phm. Planning Committee: Carlene Oleksyn, B.S.P. Pharm Tom Smiley, BScPhm, PharmD (U of T) Accreditation Information: This version of the program is unaccredited and intended for informational purposes only. An accredited version is available online at and until June 26, Sponsor: This case study is supported by an educational grant from BioSyent An accredited version is available online at and until June 26,

2 Table of Contents Anemia - A Massive Global Health Problem... 4 Learning Objectives... 4 Pre-Course Survey... 5 Case 1 Iron Metabolism, Diet and Supplementation... 6 Meet our Patient Cindy T Learning Objectives... 6 Iron... 6 Iron Absorption, Metabolism and Excretion... 7 Iron Deficiency... 8 Test your Current Knowledge... 8 Managing Iron Deficiency Dietary Modifications... 8 Revisit our Patient Cindy... 9 Managing Iron Deficiency - Supplementation... 9 Iron Supplementation Counseling Patients Starting Iron Supplements Revisit our Patient Cindy Key Learning Points Case #2 - Symptoms, Diagnosis and Laboratory Assessment of Iron Deficiency Meet our Patient Parveen S Learning Objectives Who s at Risk of Iron-Deficient Anemia? Clinical Presentation of Iron-Deficiency The Consequences of Iron-Deficiency Screening and Diagnosis of Anemia Laboratory Assessment of Anemia Complete Blood Count (CBC) Serum Ferritin Serum Iron, Iron Binding Capacity and Transferrin Saturation/Fraction Saturation The Importance of Mean Cell Volume Differences between Iron Deficient Anemia and Anemia of Chronic Disease Laboratory Monitoring of Patients on Iron Supplementation Revisit our Patient Parveen An accredited version is available online at and until June 26,

3 Key Learning Points Case #3 Pediatric Iron-Deficient Anemia Meet our Patient Kendra J Learning Objectives Iron Deficiency in Children Clinical Presentation and Consequences of Iron Deficiency in Children Recommendations for Iron Supplementation in Pediatrics Infants (0-2 years) Children 2-5 years Children 5-12 years Guideline Recommended Management of Iron-Deficient Anemia in Children Pediatric Iron Supplements Revisit Our Patient Kendra Key Learning Points Case # 4 Managing Iron Deficiency in Pregnancy Meet our Patient - Beth P Learning Objectives Iron Requirements in Pregnancy Consequences of Iron Deficiency in Pregnancy Prenatal Supplementation Anemia in Pregnancy Revisit Our Patient Beth Key Learning Points Quiz References An accredited version is available online at and until June 26,

4 Anemia - A Massive Global Health Problem Anemia is a condition marked by a deficiency of red blood cells or hemoglobin. If anemia was regarded as a disease, there is no doubt it would be one of the most common conditions in the world. 1 The World Health Organization estimates that 1.62 billion people (24.8% of the population) suffer from anemia, with iron deficiency being the most important contributing factor. 2 It is not surprising the ages most common affected are the ages of rapid growth and blood volume expansion. Globally, the most commonly affected groups include: 2 Preschool children o 47.4% have anemia globally o 7.6% in Canada Pregnant women o 41.8% have anemia globally o 11.5% in Canada Non-pregnant women o 30.2% have anemia globally o 14.3% in Canada School-age children o 25.4% have anemia globally The significance of iron-deficient anemia extends beyond simple hematological complications. The clinical consequences of iron deficiency include: 3 Decreased aerobic work performance Hair loss Developmental delay Cognitive and intellectual impairment Adverse pregnancy outcome Impaired immune function With iron deficient anemia impacting a large number of Canadians, pharmacists must be well versed on the different management strategies. With an increasing number of pharmacists having laboratory monitoring within their scope of practice, there will be increasing opportunities to intervene and manage this condition in pharmacy practice. This lesson will explore the assessment and management of iron deficient anemia in patient cases commonly seen in primary care. This should provide pharmacists with the background and management strategies to ensure their patients at risk are screened and managed appropriately. Learning Objectives Upon successful completion of this continuing education activity, you will be better able to: 1. Assess a patient presenting with common symptoms of anemia 2. Explore the different laboratory assessments required for the diagnosis of anemia An accredited version is available online at and until June 26,

5 3. Review the different non-pharmacological and pharmacological treatment options for patients with iron-deficient anemia 4. Review the management of iron-deficient anemia in patient populations at risk of iron-deficient anemia Pre-Course Survey 1. How comfortable are you in assessing a patient presenting symptoms of iron-deficient anemia? (0 not at all comfortable, 5 Very comfortable) 2. What is your current knowledge on the laboratory assessment of patients with anemia? (0 very poor, 5 excellent) 3. What is your current knowledge on the dosing and selection of products for iron-deficient anemia? (0 very poor, 5 Excellent) 4. How comfortable are you in discussing the differences between the available iron supplementations on the market? (0 not at all comfortable, 5 very comfortable) 5. What do you feel is the role of the pharmacist in the assessment and management of patients with anemia? (check all that apply) a. Screening and referring patients with symptoms of anemia b. Laboratory assessment of patients with symptoms of anemia c. Counselling patients on the non-pharmacological and pharmacological options for the management of iron-deficient anemia d. Selecting the most suitable iron supplement for a patient with iron-deficient anemia e. Managing the adverse effects and issues that arise with iron supplementation f. Other: An accredited version is available online at and until June 26,

6 CASE 1 IRON METABOLISM, DIET AND SUPPLEMENTATION Meet our Patient Cindy T. Cindy T. (22 yo) is presenting today with a new prescription for an oral contraceptive. She was recently diagnosed with iron-deficient anemia that was thought to be due to heavy menstrual bleeding. Her family physician started her on the oral contraceptive to reduce the menstrual bleeding and told her to pick up an iron supplement. Cindy is wondering if she really needs to take a supplement. Her iron is just a little low and she is on a therapy that should reduce her menstrual flow. She has also read that iron supplements have many adverse effects and she would prefer to just manage this naturally through dietary changes. She is not currently taking any other medications and has no other medical conditions. What would you recommend? Learning Objectives Upon successful completion of this continuing education activity, you will be better able to: 1. Discuss the absorption, storage and metabolism of iron 2. Recommend food sources of iron 3. Answer common questions regarding the differences between the iron supplements Iron Iron is an essential component of hemoglobin and myoglobin and thereby facilitates the transport, transitional tissue storage and cellular use of oxygen. 4 It also has important roles in the cytochromes within mitochondria and heme-containing enzymes in the body. 4 In excess, iron can be potentially toxic to cells due to its ability to catalyze the production of reactive oxygen species. 5 Tight regulation of iron uptake and storage at both the cellular and whole body levels is therefore essential. 5 The average adult male has approximately 50 mg/kg of iron and females have 35 mg/kg of iron store in their body (3-4 grams). 6 Iron containing compounds are essential and found in all cells in the body. 6 Table 1 reviews the storage of iron in the body. Table 1 Breakdown of Iron Storage in the Body 5,7 Total amount of Iron in the Body Approximately 3.5 grams Hemoglobin 2300 mg Myoglobin and other tissues (for enzyme and cytochromes) 350 mg Liver 200 mg Macrophages 500 mg Bone marrow 150 mg An accredited version is available online at and until June 26,

7 Iron Absorption, Metabolism and Excretion Figure 1 reviews the metabolism of iron in the body. In a steady state, approximately 1-2 mg of iron is loss ever day through desquamation of epithelia, but this is replaced from the amount absorbed from the daily diet. 8 Iron is constantly recycled. Macrophages in the liver, spleen and marrow phagocytose damaged erythrocytes, degrade their hemoglobin to release heme, extract iron from heme and recycle the iron to the extracellular fluid and plasma. 8 This constant recycling leads to the replacement of ml of erythrocytes that must be produced each day to maintain a steady state of red blood cells. 8 FIGURE 1 - IRON ABSORPTION, USE AND EXCRETION 8 The level of iron absorbed is affected by the iron stores. 6 During states of iron depletion, the rate of absorption can be increased by 5 to 6 fold. 5 Many factors influence the rate of intestinal absorption of iron. These include inflammation, hypoxia and pregnancy. 5 A peptide synthesized by the liver called hepcidin also affects the rate of iron absorption. It is a negative regulator of iron absorption. During periods of high iron body stores or inflammation, hepcidin levels are increased and lead to a decrease in iron absorption. 5 Once absorbed, the iron is bound to transferrin which delivers it to the different tissues in the body (Figure 1). 6 There is no physiological mechanism for iron excretion, it is lost from the body, only when cells are lost, especially epithelial cells from the GI tract, skin and renal tubules, and shedding decidua from menstrual cycles. 6 An accredited version is available online at and until June 26,

8 Normally, each of these systems work together to keep the body s iron level in a tight range. Iron Deficiency Iron deficiency occurs when the intake and absorption of iron are insufficient to replenish the body s loss. 6 Initially during periods of iron deficiency, the body relies on its iron stores to maintain red blood cell production. Once the stores are depleted, there is no longer sufficient iron to produce new erythrocytes and anemia occurs. 6 The risk factors and clinical presentation of iron deficiency are reviewed in Case #2. Test your Current Knowledge Cindy wants to know if dietary interventions would be appropriate for the treatment of iron deficient anemia. Which of the following is the MOST appropriate answer? a) Yes, but you would have to consume a large amount of legumes and meat b) Yes, once the source of anemia is addressed, diet alone should be able to replenish her iron stores c) No, diet is effective for prevention of iron deficiency but is usually ineffective when used alone for treatment d) No, diet changes are not recommend for patients with iron deficiency, due to increase in adverse effects Managing Iron Deficiency Dietary Modifications There are two main forms of dietary iron, heme and non-heme. Although both contain iron, they lead to vastly different rates of iron absorption. Heme iron is contained in meat products. 7 It is mainly found in the form of hemoglobin and myoglobin. 7 It is particularly well absorbed. Despite making up only 10-15% of the total dietary intake of iron, heme iron makes up 40% of the iron absorbed in the body. 7 The bioavailability of heme iron from food is approximately 20-30%. 7 Non-heme iron is found in vegetable products and iron-fortified cereals and foods. Unlike heme iron, this form occurs in the trivalent ferric form of iron (Fe 3+ ). 7 Non-heme iron must be converted to the ferrous form (Fe 2+ ) in an acid environment to be absorbed into the body. 7 Medications which reduce stomach acidity (e.g. proton pump inhibitors) can reduce the level of ferric to ferrous iron conversion. There are a variety of factors which can increase or decrease non-heme iron absorption (Table 2). There are several dietary interventions for the prevention of iron deficiency (Table 3). Although these interventions are effective for preventing iron deficiency, they are not as effective for the treatment of an iron deficient patient. An accredited version is available online at and until June 26,

9 Did you know? Patients using a proton pump inhibitor will experience up to a 50% reduction in non-heme iron absorption. 9 Table 2 Factors which Increase or Decrease Non-Heme Iron Absorption 7,9 Increase Non-heme Iron Absorption Decrease Non-heme Iron Absorption (Compounds which bind Iron to Prevent Absorption) Ascorbic acid Phytic acid (cereals & legumes) Citric acid Bran, wheat, rice, maize, barley, soya beans, black beans, Carotenes peas Alcohol Polyphenols (coffee, tea, cocoa, wine and some vegetables) Antacids, calcium, tetracyclines, cholestyramine Table 3 Dietary Recommendations to Increase Iron Absorption 3 Add heme iron to diet o Clams, liver, oysters, mussels, beef, shrimp, sardines, turkey/lamb Eat foods high in non-heme iron o Pumpkin seeds, tofu, infant cereal, soybeans, lentils, dark red kidney beans, fortified cereals Foods rich in ascorbic acid can assist with the absorption of non-heme iron from food Avoid polyphenol drinks and dairy products at mealtime (space out by 1-2 hours) o Tea, coffee, cocoa Implementation of these interventions can help iron deficiency from occurring in the future Revisit our Patient Cindy You explain iron absorption and metabolism, and the importance of iron for many different processes in the body. You stress that dietary intervention is an excellent idea, but it is unlikely to be able to treat her iron deficiency. She would like to discuss the different iron supplement options and would prefer a therapy with a low incidence of adverse effects. Managing Iron Deficiency - Supplementation The British Columbia Ministry of Health and international guidelines have been published on the management of management of iron deficiency. The first recommendation in a patient with iron deficient anemia is to address the underlying cause of the anemia. For example, in Cindy s case, her heavy menstrual bleeding was believed to be causing her iron deficiency. By treating her condition with oral contraceptives, we are addressing the cause. An accredited version is available online at and until June 26,

10 Iron Supplementation The treatment of iron deficiency for an adult, usually requires a dose of 180 mg of elemental iron per day. 3 Some clinicians will adjust the dose ( mg/day) based on the severity of the symptoms, ferritin levels, age of the patient and GI adverse effects. 3,10 Iron supplementation is normally continued for 4-6 months after hemoglobin levels normalize. 3 It will take several months of therapy to replenish iron stores and this ensures the patient does not return to an iron deficient state. Patient Counselling Tip Although dietary interventions to increase iron intake and absorption are still encouraged in patients taking supplements, it is important to stress that dietary interventions alone are unlikely to address iron deficiency or replenish iron stores. The majority of patients can be managed with oral iron supplements. Although intramuscular iron was used in the past, it is no longer recommended. A small portion of patients may require intravenous iron supplementation. 3 There are a number of iron supplements available in Canada. The ferrous salts (fumarate, gluconate, sulfate) have varying levels of elemental iron and different dosing schedules to reach the 180 mg/day recommendation. Two newer iron formations, polysaccharide and heme iron polypeptide tend to be better tolerated than the ferrous formulations. The different formats and dosages for each of the iron products are reviewed in Table 4. Table 4 Iron Supplementation Products 3,11 Iron Format Formulation Elemental Iron Usual Adult Dose Ferrous Sulfate 300 mg tab 60 mg/tablet 1 tablet 3 times a day Ferrous Gluconate 300 mg tab 35 mg/tablet 1-3 tablets 2-3 times a day Ferrous Fumarate 300 mg tab/cap 99 mg/tablet 1 tablet/capsule 2 times a day Polysaccharide iron 150 mg cap 150 mg/capsule 1 capsule once daily Heme iron polypeptide 11 mg tab 11 mg/tablet 1 to 3 tablets a day New Iron Formulations The ferrous salts are effective but have several shortcomings that may affect tolerability and efficacy. Two formulations have been introduced over the last several years to address many of the shortcomings of iron supplements. The key points regarding polysaccharide iron and heme iron polypeptide are reviewed in Table 5. An accredited version is available online at and until June 26,

11 Table 5 Key Points regarding Polysaccharide Iron and Heme Iron Polypeptide 11,12 Product Key Points Polysaccharide iron Iron is bound to polysaccharide complex remains soluble in a changing gastrointestinal environment Can be taken with or without food Dosing is once daily as it contains 150 mg of elemental iron Capsule can be opened and the powder can be sprinkled on food or diluted in liquid Does contain animal bi-products and may not be suitable for vegetarians o TIP: Opening the capsule and using the powder is a way to deal with this concern Generally well-tolerated in a variety of patients Heme iron polypeptide Heme iron source Can be taken with or without food Cannot be compared to standard iron doses, but therapeutic effect expected at 1 tablet 3 times daily Generally well tolerated Managing Adverse Effects of Iron Supplementation Adverse effects with iron supplementation are common. These adverse effects can affect both adherence and the maximally tolerated dose of iron products. 3 Table 6 reviews many of the most common adverse effects from iron supplements and Table 7 provides some strategies to minimize iron related adverse effects. Clinical Practice Tip Intolerance to some iron formulations is common. Consider following up with patients between 3-7 days after initiating to ensure they are able to tolerate the therapy. Table 6 Common Adverse Effects with Iron Supplements 3 Nausea Constipation Vomiting Diarrhea Dyspepsia Dark stools An accredited version is available online at and until June 26,

12 Table 7 Strategies to Manage and Minimize Adverse Effects 3,11,13 Strategy Key points Slowly increase dose Gradual initiation of iron salts (sulfate, gluconate, fumarate) start at 1/day with food increase by a tablet per week as tolerated Although this will take longer to replenish iron stores, it can dramatically increase tolerability Taking the iron supplement with food Food decreases absorption of iron salts (should ideally be taken hours after a meal) o 40% decrease in absorption o TIP- Patient may have to double dose of iron salts if taken with food Use iron supplement where absorption is not affected by food Polysaccharide iron and heme iron polypeptide are not affected by food Choose an iron supplement with higher tolerability Polysaccharide iron and heme iron polypeptide tend to be tolerated better than the iron salts Counseling Patients Starting Iron Supplements With many patients failing to take their iron supplements appropriately, it is important for pharmacists to provide strategies to ensure their patients are appropriately managed. Table 8 reviews come key counselling points pharmacists should consider providing all patients starting iron supplements. Table 8 Key Counselling Points with Iron Supplements Adherence is crucial Many patients will stop when they feel better Continue treatment for 4-6 months AFTER normalization of blood work Adverse effects are Crucial to inform patient to minimize shock (especially black stools) common Food can help, better tolerated formulations can help Daily dosage is based on elemental iron Depending on formulation, the patient may need to take several tabs/caps each day for example 300 mg of ferrous gluconate = 35 Involve the patient in the decision mg of iron All formulations are effective if taken at the appropriate dose Convenience and adverse effects could be large factors for the patient Revisit our Patient Cindy To help to manage her iron-deficient anemia, we encourage her to increase her iron intake in her diet. She should watch her tea, coffee, cola, chocolate and dairy intake with her meals as this may reduce iron absorption. We let her know that dietary interventions alone are unlikely to replenish her iron stores. We review the different iron supplements and stress that she should be taking between mg of elemental iron per day. We engage her in the treatment selection process and tailor the therapy based on convenience, adverse effects and her preference. An accredited version is available online at and until June 26,

13 Cindy would like a convenient therapy that has a lower incidence of adverse effects. We review the potential adverse effects and the need for adherence to the therapy and schedule follow-up in a few days to see how she is tolerating her iron supplement. Key Learning Points 1. Iron deficient anemia is a worldwide health problem 2. Iron from diet is available from heme and non-heme sources a. Non-heme iron absorption is affected by phytic acid and polyphenols 3. Diet alone is unlikely to replenish iron stores but can prevent iron deficiency 4. Usual dose of iron supplementation in adults is 180 mg/day but can range from mg day 5. Several iron formulations are available: a. All are effective b. Some are more convenient (less tablets per day and less frequent dosing times) c. Some are better tolerated An accredited version is available online at and until June 26,

14 CASE #2 - SYMPTOMS, DIAGNOSIS AND LABORATORY ASSESSMENT OF IRON DEFICIENCY Meet our Patient Parveen S. Parveen S. (23 yo) presents today to ask if you could help to address the way she is feeling. Over the last month or two she has been feeling tired all the time and does not have the energy to work out. She said she just does not feel like doing anything. Her mood has been fine, but is feeling tired and sluggish. Upon further questioning you determine: She has been a vegetarian since the age of 15 years She used to eat an incredibly healthy diet, but now works full-time and tends to grab a salad or junk-food for her main meal of the day Her friends told her to start taking a multivitamin every day and maybe consider a herbal preparation with ginseng. You feel that she may have iron deficient anemia, what would you do at this point? Learning Objectives Upon successful completion of this continuing education activity, you will be better able to: 1. Assess a patient for risk factors for anemia 2. Discuss the clinical presentation of a patient with iron deficient anemia 3. Review the diagnosis and laboratory assessment of a patient with symptoms of anemia 4. Determine appropriate monitoring of a patient initiated on iron supplementation Who s at Risk of Iron-Deficient Anemia? Not every patient is at risk of iron-deficient anemia. Patients are at increased risk during periods of growth (e.g. preschool children) and increased requirements (e.g. pregnancy). Patients with one or several risk factors can help clinicians to determine if the patient should be screened for iron-deficient anemia. The four major categories of iron-deficiency risk factors are reviewed in Table 9. An accredited version is available online at and until June 26,

15 Table 9 Iron-Deficiency Risk Factors by Category 3 Category Patients at risk Increased Growing infants Requirements Menstruating women Pregnancy Lactation Multiparity (giving birth to > 1 child) Parturition (giving birth) Decreased Intake Low socioeconomic status Vegetarian diet Lack of balanced diet or poor intake Alcoholism Elderly High risk ethnic group (First Nations) Increased Loss Menorrhagia GI bleeding Regular blood donors Post-operative patients with significant blood loss Hematuria Intestinal parasites (travel or immigration from an endemic area) Intravascular hemolysis: hemoglobinuria Extreme physical exercise (endurance athletes) Pathological (hemolytic anemias) Decreased Absorption Dietary factors o tannins, phytates in fibre, calcium in milk, tea, coffee, carbonated drinks Upper GI Pathology: o Chronic gastritis o Gastric lymphoma o Celiac disease o Crohn s disease Medications that decrease gastric acidity or bind iron Gastrectomy or intestinal bypass Duodenal pathology Chronic renal failure patients An accredited version is available online at and until June 26,

16 Did you know? 14,15 Some studies have shown vegetarians are at elevated risk of iron-deficiency. With the consumption of only non-heme iron, they are only absorbing a small percentage of the iron consumed in their diet. A typical vegetarian diet is also high in polyphenols and phytic acids and this can reduce the amount of iron absorbed. Consider recommending increasing ascorbic acid intake with foods high in non-heme iron, as it helps to increase absorption. Clinical Presentation of Iron-Deficiency For many patients the iron-deficiency is completely asymptomatic until the iron stores are depleted and hemoglobin and red blood cell levels start to decrease. Table 10 reviews the clinical signs and symptoms of iron-deficient anemia. When screening a patient with common signs of iron deficient anemia consider asking about other symptoms that could provide underlying clues to a possible cause of the anemia. Two of the most common concerns are gastrointestinal and gynecological symptoms such as: 16 Abdominal pain May indicate an ulcer Change in stool consistency or blood in stools May indicate a need for colon cancer screening Heavy menses Common reason for iron deficiency in women Camping May indicate potential uterine fibroids Table 10 Symptoms of Iron Deficiency 6 Common Symptoms Fatigue Inability to concentrate Irritability Weakness Pallor Palpitations Lightheadedness Headaches Tinnitus Dyspnea with minimal exertion Other Symptoms Restless legs syndrome Impaired thermoregulation Impaired immune function Hair loss Angular stomatitis (ulcerations or fissures at the corners of the mouth) Glossitis (a smooth, waxy - appearing, red tongue) Pica (obsessive consumption of substances with no nutritional value, such as ice, starch, clay, paper) Gastric atrophy Clinical Practice Tool The Iron Deficiency Anemia Checklists for Adults and Children are excellent tools to quickly screen patients for symptoms commonly associated with anemia. An accredited version is available online at and until June 26,

17 The Consequences of Iron-Deficiency Almost every cell in the body requires iron to function correctly. Adults with iron-deficiency anemia experience a significant decrease in their overall quality of life through decreased productivity, irritability and fatigue. 3 The impact on pregnant and pediatric patients is very significant: 3,17,18 Pregnancy o Associated with an increased risk low-birth weight, prematurity and maternal morbidity Children o Impaired cognitive development and behavioural problems, restlessness, ADHD, irritability, growth retardation Screening and Diagnosis of Anemia Universal screening of all patients for anemia is not recommended. 3 Screening is recommended for patients whose clinical presentation, risk factors and history indicates they may have anemia. The current recommendation is: 3 Patients in an elevated risk group with clinical signs or symptoms of anemia should be considered for blood work assessment Pharmacists are strongly encouraged to consider either ordering laboratory testing (if within their scope of practice) or refer to a physician for further assessment in symptomatic patients at risk of anemia. This early identification can many times allow for earlier treatment while the patient is only iron deficient versus waiting until they are anemic and experiencing a reduction in their quality of life. Table 11 reviews some factors to note during a patient history and conditions to consider in a patient with symptoms of anemia. Table 11 Factors to consider to Note During a History and Conditions to Consider 10 Factors to Note During a History Conditions to Consider in Patient with Anemia Symptoms Dietary information iron-deficient intake is common Consider GI investigation in a male patient or postmenopausal female with no overt cause Use of ASA or NSAIDs should be noted of blood loss Family history of iron deficient anemia or o Celiac Disease other blood disorders o Inflammatory bowel disease History of blood donation or other source of o Colorectal cancer blood loss (e.g. surgery, menstruation) o Gastric ulceration Family history of colorectal cancer (firstdegree o Urinalysis can be considered relative < 50 years or two affected first-degree relatives) Assessment for blood in urine to rule out serious conditions Previous history of iron deficient anemia Laboratory Assessment of Anemia Laboratory assessment is required for the diagnosis of anemia. Guidelines recommend the following laboratory tests: 3 Complete Blood Count (CBC) An accredited version is available online at and until June 26,

18 Serum ferritin Serum iron levels Total Iron binding capacity (TIBC) Transferrin saturation/fraction saturated Consider thyroid testing to rule out other causes Complete Blood Count (CBC) The complete blood count (CBC) provides clinicians with the measurement of many factors affected by anemia. Table 12 provides a list of measurements in a CBC which are important for the diagnosis of anemia. Table 12 CBC Measurements and Significance in Anemia Diagnosis 3 Laboratory Test Test Significance Comments Red blood cells Detect anemia Used to calculate hematocrit Hematocrit Percentage of blood volume that is red blood cells Decreased by bleeding, chronic diseases, bone marrow suppression Hemoglobin Oxygen transport capability of blood Depends on number of red blood cells and the amount in each Mean Cell Volume Important for anemia Determines microcytosis, macrocytosis, normocytosis Mean Corpuscular hemoglobin Measures weight of hemoglobin in red blood cell Hypochromic red blood cells are indicative of iron deficient anemia Serum Ferritin This is the main cellular storage protein for iron in the body. 3 It is available in small concentrations in the blood and has a strong association with total body iron stores. 3 The guidelines consider it the diagnostic test of choice. Table 13 reviews the relationship between ferritin level and iron status. Serum ferritin level may be unreliable in patients with chronic disease or malignancy. 3 Non-hematologic symptoms can occur when the serum ferritin is in the low normal range (less than 50 ug/l) and higher levels of serum ferritin do not exclude iron deficiency. 3 Table 13 Link Between Serum Ferritin and Iron Status 3 Serum Ferritin level in Adults (ug/l) Iron status < 15 Diagnostic for iron deficiency Probable iron deficiency Possible iron deficiency >100 Iron deficiency unlikely Persistently >1000 Consider test for iron overload Serum Iron, Iron Binding Capacity and Transferrin Saturation/Fraction Saturation Serum iron, iron binding capacity and transferrin saturation/fraction saturation tests are normally considered when the serum ferritin is reported as normal or high and any of the following: 3 Iron deficiency is suspected clinically An accredited version is available online at and until June 26,

19 A patient with kidney failure Chronic infection, inflammation or malignancy is present For diagnosis, clinicians should consider the following as diagnostic for iron-deficient anemia: 3 Low serum iron AND High iron binding capacity AND Transferrin saturation of < 0.15 The Importance of Mean Cell Volume There are other causes of anemia beyond iron deficiency. The mean cell volume (MCV) can help to determine if the anemia is associated microcytosis (low MCV), macrocytosis (high MCV), normocytosis (normal MCV). 3 Microcytosis o Small mean cell volume o Associated with iron-deficient anemia Normocytosis o Associated with acute blood loss, hemolytic anemia, anemia with chronic diseases or renal failure Macrocytosis o Associated with pernicious anemia, folic acid deficiency Only iron deficient anemia responds to iron supplementation. Other types of anemia will required different treatments (e.g. Vitamin B12). Differences between Iron Deficient Anemia and Anemia of Chronic Disease Iron deficient anemia and anemia associated with chronic diseases show similar clinical presentation and laboratory assessment. Table 14 reviews the laboratory differentiation of iron deficient anemia versus anemia of chronic disease. Table 14 Laboratory Differentiation of Iron Deficient Anemia versus Anemia of Chronic Disease 3 Laboratory Test Iron Deficient Anemia Anemia of Chronic Disease Hemoglobin level Low Low Inflammatory Markers Negative Raised Ferritin Low Normal/Increased Serum iron Low Low Iron binding capacity Raised Low Transferrin saturation/fraction saturation Low Low or normal Laboratory Monitoring of Patients on Iron Supplementation The role of iron supplements in the management of iron-deficient anemia is reviewed in Case #1. Laboratory monitoring is recommended to monitor patients initiated on iron supplements. Key points regarding response to therapy and ongoing monitoring are reviewed in Table 15. An accredited version is available online at and until June 26,

20 Table 15 Response to Therapy and Ongoing Monitoring of Patients on Iron Supplementation 3,18 Increased red blood cell production should be seen after 7-10 days Hemoglobin should increase by 20g/L every three weeks Anemia is normally corrected after 6-8 weeks of therapy Continue iron therapy for 4-6 months after correction of anemia If patient is not responding: o Assess iron dose and adherence o Refer to rule out major pathological cause of anemia (source of blood loss) For pharmacists, consider ordering a repeat set of labs in 3-4 weeks to assess the response to iron therapy: o If starting a low iron dose of iron salt (ferrous sulfate), you may wish to delay the lab assessment as it could take longer for the agent to improve iron levels Revisit our Patient Parveen Based on her symptoms and your discussion you decide to order laboratory assessment for Parveen. Results return in a few days and she clearly has iron-deficient anemia. You follow-up with Parveen and ask her to make an appointment so that you can discuss the need for dietary adjustments and iron supplementation for several months (4-6 months after normalization of hemoglobin). You contact her physician to inform him of the results, you will be starting her on iron supplements and you will be referring her to his office for further assessment. You reorder her labs for 4 weeks to assess her response to dietary changes and iron supplementation. Key Learning Points 1. There are many causes of iron-deficient anemia but they can be classified as a. Increased requirements, increased loss, decreased absorption or decreased intake 2. Screening should not be done in all patients, but should be considered in patients with signs and symptoms of anemia and in a major at risk group 3. Pharmacists can play a key role in identifying patients appropriate for screening and in some provinces, initiate the laboratory assessment 4. Regular monitoring while on iron therapy is crucial to assess adherence and to ensure the patient is adequately responding to the iron supplement An accredited version is available online at and until June 26,

21 CASE #3 PEDIATRIC IRON- DEFICIENT ANEMIA Meet our Patient Kendra J. Kendra (11 yo) was just diagnosed with iron deficient anemia. Her mother is concerned and was wondering if this is common in her age group. Mom is also concerned regarding the treatment. Kendra can t swallow pills and her physician warned her that the liquid has an awful taste. The physician referred Kendra and her mother to you for a recommendation for a product and dose that is appropriate for Kendra. What would you recommend? Learning Objectives Upon successful completion of this continuing education activity, you will be better able to: 1. Review the clinical presentation iron deficiency in children 2. Explore the possible complications of iron deficiency in children 3. Discuss the different iron supplements for children Iron Deficiency in Children Iron deficiency is common in any of the stages of life during periods of growth and blood volume expansion. Iron is a necessary nutrient for rapidly proliferating or differentiating tissues. Anemia is common children, especially in: 18 Premature or low birth weight babies Toddlers and preschool children Adolescents Anemia is defined as a hemoglobin concentration or red blood cell mass that is less than the fifth percentile for age. Approximately 25% of school-aged worldwide are anemic and iron deficient anemia accounts for half the cases. 19 Approximately 3% of primary school-aged children in Canada are anemic. 20 Not all children are at elevated risk. Table 16 reviews the children at elevated risk. Table 16 Children at Increased Risk of Iron Deficiency 3,19 Premature children Inadequate iron intake (especially vegetarian diets and picky eaters ) Consumption of MORE than 750 ml (24 ounces) of cow s milk per day o Cow s milk is a poor source of iron, and calcium can bind iron reducing absorption Chronic blood loss Celiac disease An accredited version is available online at and until June 26,

22 Ages of rapid growth (ages 0-3 years and adolescence) Clinical Presentation and Consequences of Iron Deficiency in Children Most children with mild anemia have no signs and symptoms. 19 The clinical presentation of iron deficiency in children is usually different from that in adults (Table 17). Table 17 Clinical Presentation of Iron Deficiency in Children Tiredness Restlessness ADHD Irritability Growth retardation Cognitive and intellectual impairment Iron deficiency can have significant consequences in pediatrics. Deficiencies of nutrients (such as iron) affect brain development and function can affect IQ level. 21 It was found that the hippocampus is particularly vulnerable to iron deficiency. 21 This is concerning as it is a central processing area for declarative learning and memory. 21 Studies have shown that iron deficiency has a negative effect on: 21 Learning Memory Affective and social behaviour Recommendations for Iron Supplementation in Pediatrics Infants (0-2 years) Healthy infants born at term have sufficient iron stores for the first 4 months of life. 22 Human milk contains very little iron and exclusively breastfed infants are at risk of iron deficiency after 4 months of age. 22 The American Academy of Pediatrics (AAP) recommends clinicians consider supplementation with 1mg/kg/day of oral iron at 4 months until iron containing foods (iron-fortified cereals) are introduced. 22 Preterm infants are at risk of developing iron deficiency. The AAP recommends that all preterm infants should have an iron intake of at least 2 mg/kg per day starting by 1 month of age through 12 months of age or until starting an iron-fortified formula or beginning complementary foods that supply the 2 mg/kg of iron. 22 If the child is exclusively breastfed, this would require supplementation. This is approximately the amount of iron supplied in iron-fortified formulas. 22 Children 2-5 years A systematic review of supplementation in this age group demonstrated that daily supplementation improved hemoglobin and ferritin levels. 23 Although there was insufficient evidence to determine the effect on anemia, iron deficiency and cognitive development, the authors stated there is an increased need for more studies in this age group. 23 An accredited version is available online at and until June 26,

23 Children 5-12 years Meta-analysis of studies in this age group found supplementation had significant benefits. 20 Supplementation was shown to: 20 Improve global cognitive scores Improve intelligence quotient (IQ) among anemic children Improve measures of attention and concentration Improve age-adjusted height among all children Improve age-adjusted weight among anemic children Reduce the risk of anemia by 50% and the risk of iron deficiency by 79% In the meta-analysis, adherence to iron supplementation was generally high. 20 Guideline Recommended Management of Iron-Deficient Anemia in Children Iron deficient anemia is associated with motor and cognitive deficits in children which may be irreversible. 3 Guidelines recommend the introduction of iron rich foods and formula to reduce the risk of iron deficient anemia. 3 Routine iron supplementation is recommended for asymptomatic children aged 6-12 months who are at increased risk. The recommended dose is 1 to 2 mg/kg/day of elemental iron (max 15 mg of elemental iron/day). 3 Recommend infants and toddlers with suspected iron deficient anemia to begin treatment. Recommended treatment dose for infants and children is 3 to 6 mg of elemental iron/kg/day in divided doses. 3 Patient Counselling Tip It is crucial when discussing iron supplementation that parents are warned to keep the products well out of the reach of children as these products can be toxic in overdose. Pediatric Iron Supplements There are currently 3 different pediatric supplements. Pharmacists are encouraged to tailor the choice of product to the needs of the patient. Some of the key factors to consider are: Taste and palpability o Very important as the child will have to take it for several months, important to assess their willingness to take the liquid o Poor taste can have a dramatic effect on adherence to therapy Ease of use o Some formulations have to be administered multiple times per day o Some formulations should be taken on an empty stomach, others can be taken with or without food Adverse effects An accredited version is available online at and until June 26,

24 o Some formulations are tolerated better than others Regularly assess the adherence and tolerability to pediatric iron formulations. If the patient has problem with taste or tolerability, consider changing the formulations. The currently available pediatric iron products in Canada are reviewed in Table 18. Table 18 Pediatric Iron Supplement formulations 3 Iron product Formulation Elemental iron Notes Ferrous Sulfate Drops 75 mg/ml Syrup 30 mg/ml Drops 15 mg/ml Syrup 6 mg/ml Ferrous Fumarate Liquid 300 mg/5ml 20 mg/ml Polysaccharide Iron Powder ¼ tsp contains 15 mg elemental iron Two formulations - drops are concentrated formulation for infants Can be dissolved in water or mixed into soft foods or powdered cereal Revisit Our Patient Kendra You stress to Kendra s mom the importance of managing iron deficiency and the risk of complications in patients with unmanaged anemia. You review the different iron supplements and engage her mother in the selection of iron supplementation based on what she feels is best for Kendra. You stress the importance of adherence to therapy, regular monitoring and set a follow-up in a week to ensure Kendra is tolerating the therapy correctly. Key Learning Points 1. Iron deficiency is common in pediatrics due to increase in blood volume due to growth 2. Iron deficiency is associated with significant complications in children 3. Iron supplementation has demonstrated to dramatically improve outcomes in anemic children including improved cognitive scores 4. Breastfed children should receive iron supplementation starting at 4 months An accredited version is available online at and until June 26,

25 CASE # 4 MANAGING IRON DEFICIENCY IN PREGNANCY Meet our Patient - Beth P. Beth (27 yo) approaches the pharmacy counter to discuss iron supplements. She is almost 6 months pregnant. She was diagnosed with iron deficient anemia several weeks ago and was prescribed ferrous sulfate 300 mg BID. She is having trouble taking this supplement as it is causing significant nausea and constipation. She is wondering if she really needs to take the supplement and if it is worth all the hassle as she will be delivering in the next few months. What would you recommend? Learning Objectives Upon successful completion of this continuing education activity, you will be better able to: 1. Counsel a patient on the complications of iron deficiency in pregnancy 2. Provide Health Canada recommendations on prenatal folic acid, iron and vitamin A intake Iron Requirements in Pregnancy Iron requirements increase dramatically during pregnancy and are the greatest around the time of birth. 9 Approximately 1200 mg of iron are required from conception through delivery: mg in the fetus 90 mg in the placenta 450 mg in erythrocyte expansion 230 mg total basal losses Maternal iron intake must not only satisfy the needs of the mother but also fetal development and accommodate for blood loss during delivery. 9 After delivery, approximately 1 mg per day of iron is lost in the breast milk, but amenorrhea may help to reduce this loss. 9 Consequences of Iron Deficiency in Pregnancy Iron deficiency has a significant impact for both the mother and child. 9 Table 19 reviews the potential complications in the mother and child. An accredited version is available online at and until June 26,

26 Table 19 Potential complications of Iron Deficiency During Pregnancy 9 Low birth weight Lowered tolerance to blood loss and infection Prematurity Decreased mother-child interactions Prenatal mortality Low iron levels in the child could affect Increased risk of maternal infections cognitive development Prenatal Supplementation It is very difficult to meet the daily requirements for some vitamins and minerals during pregnancy through diet alone. Health Canada has a list of recommendations for vitamin A, folic acid and iron intake in pregnancy. These include: 24 A daily multiple vitamin that has mg of iron A daily multiple vitamin with at least 0.4 mg of folic acid A daily multiple vitamin should not exceed 3,000 mcg of retinol activity equivalent (RAE) or 10,000 IU Anemia in Pregnancy Iron deficiency anemia is the most frequent form of anemia in pregnant women. Anemia in pregnancy is defined as: 3 1st trimester - hemoglobin of less than 110 g/l 2nd trimester - hemoglobin of less than 104 g/l 3rd trimester - hemoglobin of less than 110 g/l In patients who develop iron deficiency, they should be managed with iron supplementation. This would include mg per day of iron supplementation. 11,13 This is similar to the management of anemia in adults and is reviewed in greater detail in Case #1. If necessary IV iron is considered to be safe for the second and third trimester. 3 Revisit Our Patient Beth You discuss the importance of iron supplementation on reducing complications for both Beth and her unborn child. Many times a change in iron formulation could affect the overall tolerability. You discuss the different options and consider trying a different iron formulation that may be better tolerated. Key Learning Points 1. Iron deficiency is common during pregnancy as a result of increase in blood volume due to growth, and potential blood loss 2. Iron deficiency is associated with significant complications for the mother and fetus 3. Pregnant women should take a vitamin with iron and folic acid daily 4. Treatment of anemia in pregnancy is similar to a standard adult An accredited version is available online at and until June 26,

27 Quiz Meet Peter L. (Question 1 to 5) 52 year old 2 months after major orthopedic surgery Recovering well, but when was in for a follow-up today his physician assessed his blood work and said his iron was down Wants him to start on an iron supplement He would love your advice to help him select the most effective product You decide to provide him some basic iron and anemia education 1. You start to discuss some basic iron information with Peter. Which of the following statements is TRUE? a. Approximately 10 mg per day is absorbed from our diet b. Iron is only stored in the hemoglobin in erythrocytes c. When iron stores are high, the body actively eliminates iron d. Along with absorption, iron is also recycled in the body 2. You start to discuss the dietary sources of iron. Which one of the following statements is TRUE? a. Beef is a source of heme iron b. Heme iron absorption is affected by food intake c. Approximately 40% of non-heme iron is absorbed from dietary sources d. All of the above 3. You discuss the impact of compounds on iron absorption. Which of the following has been shown to INCREASE non-heme iron absorption? a. Calcium b. Phytic acid c. Carotenes d. Bran 4. Which of the following would be an appropriate iron dosage for Peter? a. Ferrous gluconate 300 mg twice daily b. Ferrous sulfate 300 mg three times daily c. Ferrous fumarate 300 mg three times daily d. Ferrous sulfate 300 mg once daily 5. You review each of the different formulations with Peter. He wants to know more about the two new iron formulations. Which of the following statements is TRUE regarding polysaccharide iron and heme iron polypeptide? a. These formulations are better tolerated than the traditional iron salts b. These formulations can be taken with or without food c. The usual daily dose of polysaccharide iron is 1 capsule daily d. All of the above An accredited version is available online at and until June 26,