10/1/2016. Iron Deficiency Anemia in Clinical Practice: Evaluation & Treatment Approach. Objectives. Introduction

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1 Iron Deficiency Anemia in Clinical Practice: Evaluation & Treatment Approach Simi Jesto Joseph, DNP, APN, NP-C Director of Research & Clinical Services/GI NP GI Solutions of IL Objectives To understand the pathogenesis of Iron deficiency and iron cycle To discuss the screening guidelines for IDA To learn the etiology of iron deficiency anemia To understand the algorithm for diagnosis of IDA To explain the current evaluation and treatment guidelines for IDA To discuss the unexplained refractory IDA Introduction Iron Deficiency anemia is diminished red blood cell production due to low iron stores in the body Common causes Inadequate iron intake Decreased iron absorption Increased iron demand Increased iron loss Keys to evaluation Identify underlying etiology Choose appropriate therapy 1

2 IDA IDA is the most common nutritional disorder worldwide A common medical condition in everyday clinical practice 2 billion people worldwide IDA remains the top cause of anemia (reported b/w ) Prevalence is now high in central and west Africa and south Asia Global rates has decreased due to prevention programs Developing countries(insufficient dietary intake & worms) Developed Countries (Dietary habits, chronic blood loss & malabsorption) Pathogenesis Screening Asymptomatic men and postmenopausal women should not be screened routinely Pregnant Women First & Third Trimester( hgb <11g/dl) Second Trimester (hgb <10.5g/dl) Children Universal screening at one year of age Assess risk factors-prematurity, exposure to lead, weaning to whole milk, diet 2

3 Causes Inadequate Iron Intake Decreased Iron Absorption Increased Iron Demand Increased Iron loss Causes of IDA Physiologic Infancy Rapid growth (adolescence) Menstrual blood loss, pregnancy, blood donation Environmental Insufficient intake Poverty Malnutrition Diet (vegan) Drug-related- Glucocorticoids, Salicylates, NSAIDS, PPI Genetic-Iron-refractory IDA Causes of IDA Pathologic 1) Decreased absorption-gastrectomy, duodenal bypass, bariatric surgery H-pylori infection, celiac sprue, atrophic gastritis, IBD 2) Chronic blood loss GI esophagitis, erosive gastritis, Cameron ulcer, GAVE, small bowel tumors, peptic ulcer, Diverticulitis, Benign tumor, intestinal cancer, IBD, AVM, Hemorrhoids, hook worm, obscure GIB GU Menorrhagia, intravascular hemolysis (autoimmune hemolytic anemia, Damaged heart valves, microangiopathic hemolysis) Other Systemic bleeding, hemorrhagic telangiectasias, chronic schistosomiasis Mauchausen s syndrome (self-induced hemorrhages) 3

4 Obscure GI bleed Younger <40 yrs Small bowel tumors Meckel s diverticulum Dieulofoy s lesion Crohn s disease Older >40 yrs Vascular lesions NSAID injury Common Causes of OGIB Small bowel Angioectasia Ulcers/erosions Tumors Diverticula Vessels (Raju GS et al. 2007) Angiodysplasia Increased prevalence: End stage renal disease, Von-Willebrand disease, and Aortic stenosis (Heyde s syndrome) High diagnostic yield by CE when non explanatory EGD and colonoscopy CE is superior to push enteroscopy Angiodysplasias-50% of findings Ulcers-26.8% Neoplastic lesions-8.8% Second CE lead to diagnosis up to 30-62% Kopylov & Seidman, (2013) Photography: Used with permission from (GI Solutions/Arun Ohri, MD) NSAID Enteropathy Distal small bowel and colon are affected Pathogenesis: Enteric-coated or sustained release of NSAID Enterohepatic circulation (secretion of drug into bile leads to repeated exposure to small bowel) Clinical manifestations: Subclinical and unrecognized Iron deficiency anemia Malabsorption Hypoalbuminemia Perforation or stricture Kopylov & Seidman, (2013) Diagnostic eval: Include small bowel (thin and concentric rings with strictures) Double balloon enteroscopy for biopsy Management: Discontinuing NSAIDS Surgery if complications occurs 4

5 Celiac Disease Jejunum-45% Involved in entire small bowel also Symptoms Diarrhea, abdominal pain, malabsorption, progressive anemia, GI bleeding CE findings-villous atrophy in the duodenum and jejunum, nodularity, scalloping, mosaic pattern Diagnosis EGD with duodenal biopsy Lab-tTG IgA(highly sensitive and specific) Kopylov & Seidman, (2013) Treatment: Gluten-free diet can help to reverse the villous atrophy Complications of refractory celiaculcerations, thick folds, stenosis, and severe enteropathy Photography: Used with permission from (GI Solutions/Arun Ohri, MD) MECKEL S DIVERTICULUM Congenital anomaly of GI tract Location: Mid-distal Ileum (2 feet from Ileocecal valve), 2 inch long Prevalence: children, 2 % of population Clinical features: Painless LGIB Recurrent intussusception Features of appendicitis when it s been removed Obscure GI bleed Photography: Used with permission from (GI Solutions/Arun Ohri, MD) Diagnosis/Treatment: Meckel s scan-identifies with ectopic gastric mucosa with in diverticulum (Diverticula is not visible with out that) Abdominal exploration Surgical resection only indicated for symptomatic diverticulum Death is rare Lymphagiectasias Small bowel presentation-small lacteals of individual villi, tiny punctuate white flecks on the mucosal surface Clustering of such lymphangiectasias present as bright white nodular protrusions Cystic dilatations of large lymph vessels in the mucosa and submucosa are Chylous cysts or cholesterol cysts Non-neoplastic lesions found incidentally Do not produce symptoms or cause protein loss Abnormality of lipid absorption or metabolism is unknown Kopylov & Seidman, (2013) Photography: Used with permission from (GI Solutions/Arun Ohri, MD) 5

6 Phlebectasias Focal dilations of mucosal veins Also called as venous lakes Incidental findings May increase in size and lead to occult bleeding or overt bleeding Photography: Used with permission from (GI Solutions/Arun Ohri, MD) Diagnosis Diagnosis requires lab confirmation Complete Blood count MCV-low 40% pts with IDA will have normocytic erythrocytes (cut off should be 95) Serum Ferritin-low Reflects iron stores Level <15 ng/ml Ferritin can be elevated in chronic inflammation or infection Serum iron-low Transferritin Saturation-low Iron-binding capacity-high 6

7 Diagnosis If diagnosis remains unclear Soluble transferritin receptor Indirect measure of erythropoiesis Levels are increased in IDA Benefit is, it is unaffected by inflammatory states Helpful in identifying IDA in pts with anemia of chronic disease Erythrocyte proporphyrin test Heme precursor, accumulates in the absence of adequate iron stores Bone marrow eval Absence of stainable iron confirms the diagnosis MCV <95 fl Ferritin _<30 ng/ml Increased total IBC Low serum iron level Low transferrin sat Ferritin ng/ml In patients with any other result, order soluble transferrin receptor test Ferritin >100 ng/ml Decreased total ironbinding capacity, high serum iron level, high transferrin saturation Algorithm for diagnosis of IDA Increased Normal Decreased Erythrocyte Proporphyrin Level increased? No Iron Deficiency Anemia yes No Suspicion persists; consider Bone marrow Iron Deficiency Anemia yes Low Bone marrow iron level No Work up for other causes Evaluation History & Physical Examination IDA are often asymptomatic & limited physical findings Potential etiologies, diet, GI symptoms-history of pica, pagophagia, signs of blood loss (epistaxis, menorrhagia, melena, hematuria, hematemesis) Surgical History-gastric bypass Family h/o GI malignancy Further eval should be based on risk factors 7

8 Premenopausal women Iron Deficiency Anemia diagnosed Men & Postmenopausal women Algorithm for evaluation of IDA Abnormal Uterine bleeding? No Yes Upper endoscopy, colonoscopy, small bowel capsule study, celiac serology Treat with iron Initiate work up for bleeding No evidence of GI source Evidence of GI Source If no response, initiate GI eval for OGIB Observe Treat with iron Treat underlying cause response No response Repeat GI work up Treatment Oral iron Therapy Dose Adult dose-120mg/day for three months Children- 3mg/kg/day, up to 60 mg/day Monitor-Hgb of 1g/dl after one month Duration- 3 months Side effects: GI adverse effects (epigastric pain, nausea, change in bowel habits) Better with meals but absorption is decreased by 40% Severe iron-deficiency anemia with CV symptoms-should receive red-cell transfusion (one unit provides 200mg of iron) Parenteral Iron Therapy Indications: Who cannot tolerate or absorb oral therapy(gastrectomy, gastrojejunostomy, bariatric surgery, small bowel surgeries) Rapid increase in hgb level is required-chronic blood loss IBD, celiac disease, malabsorption Renal failure-induced anemia treated with erythropoietin Side effects: Nausea, vomiting, pruritus, headache, flushing, myalgia, arthralgia, back and chest pain Usually resolves within 48 hours Slow infusion rate, observe, no premedication required (Short & Domagalski, 2013; Camaschella, 2015) 8

9 Parenteral Iron Therapy Iron Sucrose and Ferriecit has greater bio availability and low incidence of life threatening anaphylaxis Iron Dextran had serious adverse effects and fatalities reported between A new dose guideline is approved Cost is high However, number of hospital and clinic visits is significantly decreased More effective and increases hemoglobin levels more quickly than oral iron Iron Therapy Form Formulation Elemental Iron Adult Dose Intravenous Sodium Ferric Gluconate (Ferrlecit) Solution for injection 12.5 mg per ml Based on weight Iron Dextran Solution for injection 50 mg per ml Iron Sucrose Solution for injection 20 mg per ml Ferumoxytol Solution for injection 30 mg per ml Oral Ferrous Fumarate 324 mg tablet 106 mg BID Ferrous Gluconate 300 mg tablet 38 mg 1-3 tab BID or TID Ferrous Sulfate 325 mg tablet 65 mg TID Iron Deficiency Anemia diagnosed Treat underlying cause and start oral iron therapy Not tolerated Intravenous iron therapy Treatment Algorithm Monthly cbc showing improved yes HCT and red cell indices? No Continue therapy three months after hematocrit and ferritin levels normalize, then discontinue oral iron CBC performed periodically; values normal? yes No No further monitoring Reevaluate for underlying cause. Consider IV iron therapy/transfuse if symptomatic 9

10 Monitoring No standard recommendation Suggested course is to recheck CBC every three months for one year More practical approach is check periodically No further follow up when HCT levels normal and patient asymptomatic Blood transfusion Guideline (AABB) Hgb <6 g/dl Transfusion recommended except in exceptional circumstances Hgb 6 to 7 g/dl Transfusion generally likely to be indicated Hgb 7 to 8 g/dl Transfusion should be considered in postoperative surgical patients, including those with stable cardiovascular disease, after evaluating the patient s clinical status Hgb 8 to 10 g/dl Transfusion generally not indicated, but should be considered for some populations (eg, those with symptomatic anemia, ongoing bleeding, acute coronary syndrome with ischemia) Hgb >10 g/dl Transfusion generally not indicated except in exceptional circumstances (Chan & Gara, 2015) Symptomatic patient In some randomized trials of transfusion thresholds, symptoms of anemia were an indication for transfusion regardless of whether the Hgb was above the prescribed threshold. Symptomatic anemia should be treated with transfusion in all patients with Hgb <10 g/dl Acute coronary syndrome The optimal transfusion threshold in the setting of acute coronary syndromes (ACS; ie, acute MI, unstable angina) remains unresolved (Chan & Gara, 2015) 10

11 Cardiovascular disease The decision of whether to transfuse patients with cardiovascular disease should consider the nature of the cardiovascular disorder. As an example, it is possible that patients with acute coronary syndromes require different thresholds for transfusion than do patients with stable coronary artery disease or patients with congestive heart failure. Trauma/massive transfusion Use of massive transfusion in the critically ill, hemodynamically unstable patient cannot be guided by Hgb levels alone and often cannot await interval measurements of Hgb. (Chan & Gara, 2015) Intensive care unit/septic shock Restrictive transfusion appears to be safe in medical patients in an intensive care unit (ICU), with the possible exception of patients with ischemic heart disease/acute coronary syndrome. Acute bleeding Acute bleeding is an especially challenging clinical setting in which to evaluate red cell transfusion thresholds. For patients with massive bleeding or who are hemodynamically unstable, transfusion should be guided by the pace of the bleeding and the ability to stop the bleeding, rather than by the Hgb. (Chan & Gara, 2015) Anemia in Elderly Observational studies suggests, it is ineffective Absorption of oral iron from the aged gut may be poor due to atrophic gastritis Most older pts are also on PPI therapy Widely used for the tangible benefits Improve quality of life Lower morbidity & mortality Cappellini & Motta, 2015; Tay & Soiza, 2015) 11

12 Refractory IDA Definition: Failure to respond to tx 100mg of elemental iron 4-6 weeks Anemia persists after a negative GI work up High risk pts-complete GI work up including small bowel capsule study Low risk pts- Evaluate the role of H-pylori gastritis, Autoimmune gastritis, Celiac disease, and Hereditary Iron-refractory IDA Finally-Hematology consult and monitoring by heme (Hershko & Camaschella, 2013) Hereditary Iron Refractory IDA (IRIDA) Autosomal recessive disorder-caused by mutations on the transmembrane serine protease 6 gene encoding (TMPRSS6) MT-2 is a transmembrane serine protease essential for down regulating hepcidin, the master regulator of iron homeostasis This function is impaired in mutations involved in above gene. Serum hepcidin will be inappropriately high Patients are unable to respond to iron therapy (Hershko & Camaschella, 2013) References Camaschella, C. (2015). Iron-Deficiency Anemia. The New England Journal of Medicine;372: Cappellini, D.M. & Motta, I. (2015). Anemia in Clinical Practice-Definition and Classification: Does hemoglobin change with aging?. Seminars in Hematology; 52(4): Chan, A.W. & Gara, CJ. De. (2015). An evidence-based approach to red blood cell transfusions in asymptomatically anemic patients. Ann R Col Surg Engl; 97: Hershko, C. & Camaschells, C.(2013). How I treat unexplained refractory iron deficiency anemia. Blood;123(3): Raju GS et al. American Gastroenterological Association (AGA) Institute Medical Position Statement on Obscure Gastrointestinal Bleeding. Gastroenterology 2007;133: Kopylov, U. & Seidman, E.G. (2013). Clinical applications of small bowel capsule endoscopy. Clinical and Experimental Gastroenterology, 6: Short, M.W. & Domagalski, J.E. (2013). Iron Deficiency Anemia: Evaluation and Management. American Family Physician; 87(2): Tay, H.S. & Soiza, R. L. (2015). Systematic Review and Meta-Analysis: What is the evidence for oral supplementation in treating anemia in elderly people? Drugs Aging; 32:

13 Thank you 13