Anemia Management 2023 PDF

Management of Iron, Vitamin B12, and Folate Deficiency Anemias Integrated Hematology/Oncology Module - PHAR 5367 Shantera Rayford Davis, PharmD, BCPS Clinical Assistant Professor University of Houston College of Pharmacy January 16, 2024 Spring 2024 Objectives Differentiate Recognize Identify Sele...

Management of Iron, Vitamin B12, and Folate Deficiency Anemias Integrated Hematology/Oncology Module - PHAR 5367 Shantera Rayford Davis, PharmD, BCPS Clinical Assistant Professor University of Houston College of Pharmacy January 16, 2024 Spring 2024 Objectives Differentiate Recognize Identify Select Identify Select Differentiate between different types of anemia, their etiologies, and pathophysiology Recognize signs and symptoms of anemia Identify food sources rich in iron, vitamin B12, and folate Select patient-centered goals of therapy and treatment with followup monitoring for iron, vitamin B12, and folate deficiency anemias Identify efficacy and safety monitoring parameters and drug-drug interactions Select pertinent patient counseling points for oral iron, vitamin B12, and folate therapy Lecture Roadmap General anemia information Evaluation of signs and symptoms of anemia Laboratory evaluation of anemias Iron deficiency anemia Vitamin B12 deficiency anemia Folate deficiency anemia What is anemia? What is anemia? Anemia is a group of diseases characterized by: Decreased hemoglobin (Hgb) or red blood cells (RBCs) which results in and is defined by the World Health Organization (WHO) as: Decreased oxygencarrying capacity of the blood Cook KM, Greer DM. Anemias. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw-Hill; Accessed January 12, 2021. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577&sectionid=233055533 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Anemia Hgb <13 g/dL in men and <12 g/dL in women Morphologic Classification of Anemias • Normocytic anemia (MCV = 80 – 100 fL) – Chronic disease – Blood loss • Microcytic anemia (MCV < 80 fL) – Iron deficiency anemia (IDA) • Macrocytic anemia (MCV > 100 fL) – B12 deficiency anemia – Folate deficiency anemia MCV = Mean cell volume What signs and symptoms support the presence of an anemia? Signs and Symptoms Associated with Anemia • Patients may be asymptomatic • Dependent on the rate of anemia development, age, and cardiovascular status • Result from decreased oxygen delivery to tissues Signs and Symptoms Associated with Anemia Acute anemia • Likely to present with cardiopulmonary symptoms (NOTE: s/sxs of chronic anemia can also be present): – – – – – Tachycardia Angina Lightheadedness Dyspnea Hypotension Chronic anemia • • • • • • • • Weakness Fatigue Headache Dizziness Decreased mental acuity Pallor Sensitivity to cold Exercise intolerance Signs and Symptoms Associated with Anemia IDA • May also present with (not likely to appear unless anemia is severe): – Glossal pain – Smooth tongue – Pica – Pagophagia Vitamin B12 deficiency anemia • May also present with neurological impairment (not likely to appear until significant B12 deficiency): NOTE: Folate deficiency is less likely to lead to neurological impairment – – – – – Numbness Paresthesia Ataxia Memory impairment Vision changes What laboratory parameters are needed to evaluate the presence of an anemia? Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy Complete Blood Count (CBC) with reticulocyte count to evaluate all suspected anemias Consistent with microcytic anemia (i.e., MCV < 80 fL) Obtain and evaluate iron studies Consistent with macrocytic anemia (i.e., MCV > 100 fL) Obtain and evaluate serum vitamin B12 and folate levels Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy • CBC with reticulocyte count Hemoglobin Hematocrit Red blood cell (RBC) count Red blood cell indices (provide information on the physical features of RBCs) • Mean cell volume (MCV) • Mean cell hemoglobin (MCH) • Mean cell hemoglobin concentration (MCHC) • Red cell distribution width (RDW) Reticulocyte count White blood cell count Platelet count General lab parameters to evaluate all suspected anemias Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy • Hemoglobin (Hgb) – One of the parameters that can be used to determine the presence of anemia – Measured amount of Hgb in a unit volume of blood – Normal: 13 to 17 g/dL (men) and 12 to 15 g/dL (women) Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy • Hematocrit (Hct) – Calculated percentage of RBCs in a unit volume of blood (generally 3 times the Hgb value when Hgb is expressed as g/dL) – Normal: 40 – 52% (men) and 36 – 47% (women) • RBC count – One of the parameters that can be used to determine the presence of anemia – Actual count of RBCs per unit of blood – Normal: 4.7 – 6.1 X 106 cells/microliter (men) and 4.2 – 5.4 X 106 (women) Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy Red Blood Cell Indices Mean cell volume (MCV) Key Details • • • • Clinical Implications Normal: 80 – 100 fL Calculated as: Hct/RBC count Represents the average volume of RBCs = the average RBC size Most important for differentiating between anemias • • • ↔ MCV = normocytic ↓ MCV = microcytic ↑ MCV = macrocytic Mean cell hemoglobin (MCH) • • • Normal: 27 – 31 pg/cell Calculated as Hgb/RBC count Represents the average amount of Hgb in a RBC, usually increases and decreases with the MCV • • ↔ MCH = normochromic ↓ MCH= hypochromic Mean cell hemoglobin concentration (MCHC) • • • Normal: 32 – 36 g/dL Calculated as Hgb/Hct Represents the concentration of Hgb per volume of RBCs • • ↔ MCHC = normochromic ↓ MCHC = hypochromic Red cell distribution width (RDW) • • Normal: 11.4 – 13.5% Represents the variation in RBC size • ↑ implies a large variation in RBC sizes ↔ implies homogeneity • Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy • Reticulocyte count – Normal: 0.5 – 1.5% – Indirect assessment of new RBC production – Reflects how quickly immature RBCs (reticulocytes) are produced by the bone marrow and released into the circulation Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy Complete Blood Count (CBC) with reticulocyte count to evaluate all suspected anemias Consistent with microcytic anemia (i.e., MCV < 80 fL) Obtain and evaluate iron studies Consistent with macrocytic anemia (i.e., MCV > 100 fL) Obtain and evaluate serum vitamin B12 and folate levels Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy Additional Parameters to Evaluate Iron Deficiency Anemia (IDA) Key Details Clinical Implications Serum iron • • • Normal: 60 – 150 mcg/dL Circulating iron, mostly bound to transferrin May remain within the lower limits of normal due to iron stores Decreased in IDA Ferritin • • • Normal: 40 – 200 ng/mL Circulating iron storage protein Earliest and most sensitive indicator of iron deficiency – may not be reliable in inflammatory process since it is an acute phase reactant Decreased in IDA Total iron binding capacity (TIBC) • • • Normal: 300 – 360 mcg/dL Measures the total amount of iron that can be bound by transferrin TIBC is the clinically used measurement for transferrin (transport protein for iron) Increased in IDA Transferrin saturation (TSAT) • • • Normal: 20 – 50% Calculated as serum iron/TIBC X 100 Reflects the extent to which iron-binding sites are occupied on transferrin and indicates the amount of iron readily available for erythropoiesis Decreased in IDA (≤15%); less sensitive and specific marker Laboratory Parameters to Evaluate Anemia Help to guide diagnosis and assess drug therapy Additional Parameters to Evaluate Vitamin B12 and Folate Deficiency Anemias Serum vitamin B12 Key Details • • • <200 pg/mL = deficient 200 – 300 pg/mL = borderline >300 pg/mL = normal Clinical Implications • • • Serum folate • • • Folate: <2 ng/mL = deficient 2 to 4 ng/mL = borderline >4 ng/mL = normal • A deficiency may exist prior to the recognition of low serum levels Serum values are maintained at the expense of sequestering vitamin B12 from tissue stores Vitamin B12 and folate deficiency may overlap, thus serum levels of both vitamins should be determined May coexist with a vitamin B12 deficiency anemia, thus serum levels of both vitamins should be determined Putting the Lab Data Together Hgb <13 g/dL in men and <12 g/dL in women MCV <80 fL MCV >100 fL Microcytic anemia Serum iron low, ferritin low, TIBC elevated, TSAT low Iron deficiency anemia (IDA) Vitamin B12 level <200 pg/mL Folate level <2 ng/mL Vitamin B12 deficiency anemia Folate deficiency anemia Assessment of Anemia Signs/Symptoms Symptoms generally consistent with acute anemia but can be present in chronic anemia: • Tachycardia/palpitations • Lightheadedness • Dyspnea/breathlessness • Hypotension Symptoms generally consistent with chronic anemia but can be present in acute anemia: • Weakness • Fatigue • Headache • Vertigo • Pallor • Sensitivity to cold Possible manifestations specific to IDA (not likely to appear unless anemia severe): glossal pain, smooth tongue, pica, and pagophagia Possible manifestations specific to B12 deficiency anemia: numbness, paresthesia, personality changes, memory impairment, ataxia, vision changes Vital Signs • BP • HR • RR Laboratory Findings • CBC with reticulocyte count • RBC indices include: • MCV – guides diagnosis • MCH • MCHC • RDW • Iron studies (serum iron, ferritin, TIBC, TSAT) • Serum B12 • Serum folate Assessment of Anemia in Practice Summary Evaluate signs and symptoms of anemia Evaluate vital signs (likely affected in acute anemia vs. chronic anemia) Monitor efficacy and safety parameters at appropriate follow-up intervals Evaluate laboratory findings Select appropriate treatment regimen Iron Deficiency Anemia Iron Background • Iron deficiency – most common nutritional deficiency in developing and developed countries • Prevalence in women of childbearing age is 4.5% • Normal iron content of the body is ~3 – 4 g • Most people lose ~1 mg of iron daily Iron Background • Iron absorption – Absorbed primarily in the duodenum – Best absorbed in its ferrous form (Fe2+) – Heme iron (meat, fish, poultry) absorbs better than nonheme (e.g., vegetables, nuts, dietary supplements) – Gastric acid and acidic dietary components promote iron absorption (think about drug interactions!) – Caffeinated beverages reduce iron absorption (e.g., coffee, tea) – Circulates in the blood bound to transferrin Etiology of IDA • Results from prolonged negative iron balance due to: Blood loss: heavy menstrual flow, peptic – Increased iron demand ulcer disease, postpartum bleeding, trauma, GI malignancy, diverticular disease – Increased loss – Decreased intake or absorption – think about drug interactions! • Patients at risk: children <2 y/o, adolescent girls, pregnant/ lactating females, >65 y/o Pathophysiology of IDA • Hematological manifestations of iron deficiency occur in three stages: – 1st: Iron stores are reduced without reduced serum iron levels – 2nd: Iron stores are depleted (i.e., iron deficient), and Hgb is above the lower limit of normal for the population but may be reduced for a given patient – 3rd: Depleted iron stores + Hgb falls to less than normal values → IDA Laboratory Diagnosis of IDA • Two-step process: – 1st step: Obtain and evaluate the patient’s CBC for the presence of a microcytic anemia – 2nd step: If microcytic anemia is present, obtain and evaluate the patient’s iron studies Laboratory Diagnosis of IDA Step 1: Obtain and evaluate CBC Step 2: If CBC is consistent w/microcytic anemia, obtain and evaluate iron studies Parameter High or Low Parameter High or Low Hgb Low Serum iron Low Hct Low Ferritin Low RBC Count Low TIBC High MCV Low TSAT Low Microcytic anemia Iron deficiency Iron deficiency anemia Treatment of IDA • Goals of therapy – Correct the underlying etiology (from a pharmacist perspective) – Alleviate signs and symptoms (tailor to the patient) – Reverse hematological parameters to normal – Prevent recurrence of anemia – Manage medication-related problems Treatment of IDA • Nonpharmacological treatment – Avoid or minimize foods and drinks that decrease iron absorption – Counsel patient on foods rich in iron Daily recommended iron dietary allowance: • Menstruating females – 18 mg • Adult men/ • postmenopausal females – 8 mg • Pregnancy – 30 mg/day Dietary Iron Sources Serving Size Amount (mg) Ready to eat cereal, 100% fortified 3/4 cup 18 Instant plain oatmeal, fortified 1 cup 11 Wheat germ 1 oz 2.6 Broccoli 1 medium stalk 2.1 Baked potato 1 medium 2.7 Raw tofu ½ cup 4 Lentils ½ cup 3.3 Beef chuck 3 oz 3.2 Treatment of IDA • Oral iron supplementation is the mainstay of treatment • Dosing depends on the school of thought: – Traditional adult dosing of iron for IDA = 150 to 200 mg of elemental iron PO daily in 2 – 3 divided doses to maximize tolerability and absorption – New data favor smaller doses (e.g., ferrous sulfate 325 mg) either every other day or daily to maximize absorption – Actual dose of PO iron replacement depends on the patient’s ability to tolerate the dose Treatment of IDA Oral Iron Products Iron Salt Ferrous sulfate % Elemental Iron Common Formulations 20% 324–325 mg tablet Also available in liquid formulations (syrup and elixir) Ferrous sulfate (exsiccated) slow-release product AVOID USE WHEN POSSIBLE 30% 200 mg tablet 160 mg tablet Ferrous gluconate 12% 240 mg tablet, 324 mg tablet Ferrous fumarate 33% 325 mg tablet 100% Various formulations; all 100% elemental iron Carbonyl iron, polysaccharide iron complex, ferric maltol Treatment of IDA • Oral iron administration considerations – All preparations are absorbed similarly • EXCEPTION: enteric coated and slow release/sustained release products-avoid these products when possible • Maximal absorption occurs in the duodenum, primarily due to the acidic medium of the stomach – Iron is preferably administered at least 1 hour before meals because food can interfere with absorption NOTE: many patients take iron with food to minimize GI upset – Can be taken with ascorbic acid or orange juice to enhance absorption Treatment of IDA • Oral iron duration of treatment – At least 3 to 6 months after hgb normalizes to replenish iron stores; can be as long as 12 months after hgb normalizes • Therapy should be continued until ferritin and TSAT are within the normal range. Once within normal range, therapy can be discontinued • Longer duration may be required for patients with ongoing blood loss (e.g., inflammatory bowel disease, gastric/duodenal ulcer, diverticulitis, menorrhagia) Follow-up for IDA--Efficacy Monitoring • Monitoring the efficacy of oral iron drug therapy – Re-evaluate s/sxs and CBC parameters 2 weeks after starting therapy and then monthly until stable – At the 2-week point, hgb should be increased by ≥1 g/dL; hgb returns to normal after 6 – 8 weeks of treatment – Iron studies can be re-evaluated in 8 – 12 weeks and q 3 – 6 months until stable When should you expect to see a response? • • • • Improved feeling of well-being in the first few days of treatment Reticulocytosis peaking in 7 to 10 days Hgb generally rise ~1 g/dL per week, but should definitely be increased by ≥1 g/dL at the 2-week point Ferritin and TSAT normalization within 3 – 6 months Drug-Drug Interactions That Affect the Efficacy of Oral Iron Therapy Drug-Drug Interaction with Oral Iron Net Effect on Oral Iron Strategy to Minimize Interaction Monitoring Al-, Mg-, HCO3, Ca2+ containing antacids Decreased iron absorption and efficacy Give PO iron 2 hours before antacid dose Efficacy monitoring parameters for IDA → signs/symptoms, CBC, iron studies Tetracyclines Decreased iron absorption and efficacy Give PO iron 2 hours before or 4 hours after tetracycline dose Efficacy monitoring parameters for IDA → signs/symptoms, CBC, iron studies Oral histamine2 antagonists (H2RAs) Decreased iron absorption and efficacy Discontinue H2RA if not clinically necessary; Monitor signs/symptoms, CBC, iron studies if unable to discontinue Oral proton-pump inhibitors (PPIs) Decreased iron absorption and efficacy Discontinue PPI if not clinically necessary; Monitor signs/symptoms, CBC, iron studies if unable to discontinue Oral Iron Drug-Drug Interactions That Affect the Efficacy of Other Drugs Drug-Drug Interaction with Oral Iron Net Effect on the Interacting Drug Strategy to Minimize Interaction Monitoring Levodopa Decreased absorption Separate administration by at and efficacy of least 2 hours levodopa Worsening of Parkinson symptoms Oral fluoroquinolones Decreased absorption and efficacy of oral fluoroquinolones Depends on the quinolone – Signs/symptoms of administer 4 hours before and 2 infection progression to 8 hours after PO iron dose Oral levothyroxine Decreased absorption and efficacy of oral levothyroxine Separate administration by at least 4 hours Worsening of hypothyroidism signs and symptoms Oral tetracyclines Decreased absorption and efficacy of oral tetracyclines Give PO iron 2 hours before or 4 hours after tetracycline dose Signs/symptoms of infection progression Follow-up for IDA--Safety Monitoring • Adverse reactions (safety parameters) – Abdominal pain, constipation, nausea/vomiting, dark feces • Typically dose related and similar amongst iron salts • Strategies to minimize GI effects: administer smaller amounts of iron with each dose, reduce the daily dose, or administer with meals NOTE: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under age 6 – always counsel patients to keep out of reach of children Non-Responders to Oral Iron • Reasons for response failure – – – – – – Patient is nonadherent Coexisting disease interfering with marrow response Patient is not iron deficient; possibly another diagnosis is responsible Drug-drug interactions impacting absorption → efficacy Iron is not being absorbed; consider parenteral iron therapy Continued blood loss or need cannot be met by oral iron therapy Vitamin B12 Deficiency Anemia Vitamin B12 Background • Vitamin B12 (cobalamin) is a water-soluble vitamin • Obtained exogenously by ingestion of meat, fish, poultry, dairy products, and fortified cereals • Along with folate, helps to catalyze reactions essential for erythropoiesis, synthesis and maintenance of myelin, and synthesis of DNA and RNA Vitamin B12 Background • Vitamin B12 absorption • Transported via intrinsic factor to the distal ileum where it is absorbed • Passive absorption, which is independent of intrinsic factor or an intact terminal ileum, accounts for 1% of absorption in the distal ileum • The body stores several years of vitamin B12, of which ~50% is in the liver Vitamin B12 Deficiency Anemia • Most common of the two macrocytic megaloblastic anemias (folate deficiency anemia is the other macrocytic megaloblastic anemia) • Most likely to be chronic vs. acute • Risk increases with age • Patients can present with neurological symptoms Etiology of B12 Deficiency Anemia • Inadequate dietary intake – Vegans and their breast-fed infants – Chronic alcoholics • Malabsorption – – – – – Loss of intrinsic factor (such as in pernicious anemia) Chronic gastritis (such as in H. pylori infection) Food cobalamin malabsorption Gastric surgery (e.g., gastric bypass, small bowel surgery) Long-term use of certain medications (H2RAs, PPIs, metformin) Pathophysiology of B12 Deficiency Anemia Vitamin B12 and folate, in different ways, catalyze the synthesis of nucleic acids during the red blood cell maturation process Vitamin B12 deficiency impairs DNA synthesis in the RBC nucleus → leads to the production of immature, large RBCs (macrocytes) Macrocytic RBCs are larger than normal RBCs, have an oval shape (macroovalocytes) vs. a biconcave shape, and are more fragile Peripheral Blood Smear Laboratory Diagnosis of B12 Deficiency Anemia • Two-step process: – 1st step: Obtain and evaluate the patient’s CBC for the presence of a macrocytic anemia – 2nd step: If macrocytic anemia is present, obtain and evaluate the patient’s serum B12 and serum folate levels Laboratory Diagnosis of B12 Deficiency Anemia Step 1: Obtain and evaluate CBC Parameter High or Low Hgb Low Hct Low RBC Count Low MCV High Macrocytic anemia Step 2: If CBC is consistent w/macrocytic anemia, obtain and evaluate serum B12 and folate Parameter High or Low Serum B12 Low Serum folate Normal B12 deficiency B12 deficiency anemia Treatment of B12 Deficiency Anemia • Goals of therapy – Correct the underlying etiology (from a pharmacist perspective) – Alleviate signs and symptoms (tailor to the patient) – Reverse hematological parameters to normal – Prevent recurrence of anemia – Manage medication-related problems Treatment of B12 Deficiency Anemia • Nonpharmacological treatment – Counsel patient on foods rich in vitamin B12 Daily recommended B12 dietary allowance: • Adults – 2 mcg • Pregnant/breastfeeding – 2.6 mcg • Average western diet provides 5 to 15 mcg daily, of which 1 to 5 mcg is absorbed Dietary B12 Sources Serving Size Amount (mcg) Breakfast cereal, fortified (100%) ¾ cup 6 Rainbow trout, cooked 3 oz 3.5 Sockeye salmon, cooked 3 oz 4.9 Beef, cooked 3 oz 2.1 Breakfast cereal, fortified (25%) ¾ cup 1.5 Clams, cooked 3 oz 84.1 Milk 1 cup 1.2 Yogurt 8 oz 1.1 Treatment of B12 Deficiency Anemia • Early treatment is critical – Neurological damage may be irreversible if the deficiency is not detected and corrected within months • Treat underlying etiology (e.g., H. pylori) • Dietary replacement is appropriate for those whose deficiency is secondary to diet Treatment of B12 Deficiency Anemia • Vitamin B12 (cyanocobalamin) replacement options – Various dosing strategies – 1,000 to 2,000 mcg PO Daily – 1,000 mcg IM Daily X 1 week, then weekly X 1 month, then monthly (NOTE: IM is preferred when neurological symptoms or symptomatic anemia is present) Duration of Therapy If the underlying etiology can be reversed, treatment can be discontinued after the deficiency has been corrected If the underlying etiology cannot be reversed, lifelong treatment is required Follow-up for B12 Deficiency Anemia--Efficacy Monitoring • Monitoring the efficacy of B12 drug therapy – Re-evaluate s/sxs, CBC, and serum B12 level • Inpatient: s/sxs + CBC daily and B12 level in 1 – 2 days • Outpatient: 1 month after starting therapy, then every 3 – 6 months until deficiency resolved When should you expect to see a response? • Improved feeling of well-being in the first few days of treatment • Reticulocytosis within 7 days • Hgb generally rise ~1 g/dL per week and should normalize in 1 – 2 months Folate Deficiency Anemia Folate Background • Folate (folic acid) – Water-soluble B9 vitamin (folate is naturally occurring and folic acid is the synthetic form) – Along with vitamin B12, catalyze reactions essential for DNA and RNA synthesis – Obtained exogenously by ingestion of fortified cereals, dairy, mushrooms, yeast, fresh green leafy vegetables, and citrus fruits Folate Background • Folic acid absorption – Most folate in food is present in the polyglutamate form, which must be broken down into the monoglutamate form prior to absorption in the jejunum – Once absorbed, dietary folate must be converted to the active form tetrahydrofolate through a cobalamin-dependent reaction (synthetic folic acid does not require cobalamin) Folate Background • Prevention of neural tube defects – Folic acid 400 to 800 mcg/day is recommended in women planning or capable of becoming pregnant – Women with a personal or family history of neural tube defects should take folic acid 4 mg PO daily when planning pregnancy Etiology of Folate Deficiency • Inadequate intake – Elderly – Junk food diet – Chronic alcoholism • Decreased absorption – Malabsorption syndromes – Drug-drug interactions • Increased folic acid requirements – Pregnancy – Growth spurts – Chronic inflammatory disorders (e.g., Crohn’s disease) Pathophysiology of Folate Deficiency Anemia Vitamin B12 and folate, in different ways, catalyze the synthesis of nucleic acids during the red blood cell maturation process Folate deficiency impairs DNA synthesis in the RBC nucleus → leads to the production of immature, large RBCs (macrocytes) Macrocytic RBCs are larger than normal RBCs, have an oval shape (macroovalocytes) vs. a biconcave shape, and are more fragile Laboratory Diagnosis of Folate Deficiency Anemia • Two-step process: – 1st step: Obtain and evaluate the patient’s CBC for the presence of a macrocytic anemia – 2nd step: If macrocytic anemia is present, obtain and evaluate the patient’s serum B12 and serum folate levels Laboratory Diagnosis of Folate Deficiency Anemia Step 1: Obtain and evaluate CBC Parameter High or Low Hgb Low Hct Low RBC Count Low MCV High Macrocytic anemia Step 2: If CBC is consistent w/macrocytic anemia, obtain and evaluate serum B12 and folate Parameter High or Low Serum B12 Normal Serum folate Low Folate deficiency Folate deficiency anemia Treatment of Folate Deficiency Anemia • Goals of therapy – Correct the underlying etiology (from a pharmacist perspective) – Alleviate signs and symptoms (tailor to the patient) – Reverse hematological parameters to normal – Prevent recurrence of anemia – Manage medication-related problems Treatment of Folate Deficiency Anemia • Nonpharmacological treatment – Counsel patient on foods rich in folate Dietary Folate Sources Daily recommended folate dietary allowance: • Nonpregnant females and men: 400 mcg/day • Pregnant females: 400 – 800 mcg/day • Lactating females: 500 mcg/day Serving Size Amount (mcg) Beef liver 3 oz 215 Cereal, 25% fortified ½ to 1½ cups 100 – 400 Lentils, cooked ½ cup 180 Chickpeas ½ cup 141 Asparagus ½ cup 132 Spinach, cooked ½ cup 131 Pasta, enriched ½ cup 83 Orange 1 medium 47 Treatment of Folate Deficiency Anemia • Folic acid replacement (typically PO; IV therapy rarely required) – 1 to 5 mg PO Daily Duration of Therapy If underlying etiology can be reversed, treatment can be discontinued after 4 months if the deficiency has been corrected If the underlying etiology cannot be reversed, lifelong treatment is required Follow-up for Folate Deficiency Anemia--Efficacy Monitoring • Monitoring the efficacy of folic acid drug therapy – Re-evaluate s/sxs, CBC, and folate level • Inpatient: daily CBC + folate level in 1 – 2 days • Outpatient: 1 month after starting therapy, then every 3 – 6 months until deficiency resolved (may be more frequent if patient not responding to therapy) When should you expect to see a response? • Improved feeling of well-being in the first few days of treatment • Reticulocytosis within 7 days • Hgb generally rise ~1 g/dL per week and should normalize in 1 – 2 months General Counseling Points • Tell the patient: – Adherence to treatment is key to treating anemia – Continue taking therapy even if you start to feel better – Let your provider know if your symptoms continue or worsen – Iron therapy: let your provider know if you experience stomach upset or constipation – Follow up with lab work according to the provider’s recommendation Management of Iron, Vitamin B12, and Folate Deficiency Anemias Integrated Hematology/Oncology Module - PHAR 5367 Shantera Rayford Davis, PharmD, BCPS Clinical Assistant Professor University of Houston College of Pharmacy January 17, 2023 Spring 2023 Test Guidance The test questions will assess your ability to demonstrate the lecture objectives. Make sure you can perform the lecture objectives What you need to memorize • Key hematological changes (i.e., ↓, ↑, ↔) seen in iron, B12, and folate deficiency anemias (CBC, serum iron, ferritin, TIBC, TSAT, B12 level, folate level) – the normal range for the values will be provided • Signs and symptoms of anemia (including the ones specific to iron and B12 deficiency anemias) • Percent of elemental iron for each iron salt form (sulfate, gluconate, and fumarate, carbonyl iron, polysaccharide iron complex, ferric maltol) and how to calculate the percent of elemental iron in an iron dosing regimen What you need to memorize • Duration of treatment for all anemias • Parameters used to monitor efficacy for all anemias • Adverse events (safety parameters) associated with oral iron therapy and appropriate management • Drug interactions associated with oral iron therapy and appropriate management • Pertinent counseling points based on patient and drug-related factors FYI (i.e., will not be on the test) Intravenous Iron Preparations Parenteral Iron Preparations Iron sucrose Brand Name Venofer Sodium ferric gluconate Ferrlecit Ferumoxytol Feraheme Ferric carboxymaltose (FCM) Injectafer Low molecular weight iron dextran InFed Some are approved for IM injection. Recommend against IM injection because it is painful, and the preparation can permanently stain the buttocks Adverse Reactions Dosing Doses are expressed in terms of elemental iron; products vary based on elemental iron/mL, cumulative dose per course, need for a test dose, and infusion duration • • • • • • • Anaphylaxis Dizziness Hypotension Hypertension Myalgia Chest pain Chills NOTE: Iron dextran parenteral preparations have been associated with more anaphylactic reactions (particularly high molecular weight iron dextran, which is no longer on the market). All parenteral iron preparations carry a risk for anaphylactic reactions but likely to a lesser extent than iron dextran. Some institutions require premedications for certain patient populations. Do not use in patients with active infection. Intravenous Iron for IDA • IV iron preparations can be used in specific situations: – Poor adherence/intolerance to oral iron therapy – Ongoing blood loss that exceeds repletion capacity of oral iron therapy – Malabsorption – Coexisting inflammatory state that interferes with iron homeostasis – Clinical need to replenish iron stores in a short frame of time vs. months