ANEMIA - PART I Overall Approach and Iron Deficiency Anemia BY: Zorawar Noor 4/21/2014

Objectives  Understand signs and symptoms of anemia  Use 4 simple steps to classify anemia  Learn about the causes of iron deficiency anemia  Learn the lab findings in iron deficiency anemia

MKSAP Case 1  A 77-yo man is evaluated for a 1-year history of extreme fatigue and SOB on exertion and 8 weeks of substernal CP with exertion.  On Physical Exam, T 36.7C, BP 137/78, HR 118, BMI 27, Patient has pale conjunctiva, cardiopulmonary examination with summation gallop and crackles at lung bases.  Laboratory studies: Hgb 5.4, WBC 6400, MCV 58, Plt 154,000, RDW 25  Echocardiogram is normal.  Peripheral blood smear …

… MKSAP Case 1

 Which of the following is the most likely diagnosis?  (A) G6PD deficiency  (B) Iron Deficiency  (C) Myelofibrosis  (D) TTP

What is Anemia?  Reduction of Hgb, Hct, or RBC count  Or 2 standard deviations below the mean  Or in Men Hg < 13 in men and Hg < 12 in women  (WHO criteria)

Signs and Symptoms  Asymptomatic  Tachycardia  Dyspnea on Exertion  Pallor of nails and conjunctivae  Nail spooning  Fatigue  Decreased exercise tolerance  Pica

Physical Manifestation : “Spoon Nails” in Iron Deficiency

Reasons for Anemia  1) Blood Loss  2) Underproduction of Erythrocytes  3) Destruction of Erythrocytes (hemolysis)

4 Steps to Classify Anemia  Step 1 – Characterize by MCV  Step 2 - Identify Morphologies on Peripheral Smear  Step 3 – Calculate Reticulocyte Index  Step 4 – Use iron studies, bone marrow biopsy, etc.

Step 1  Step 1- Characterize by MCV:  Microcytic (MCV < 80)  Reduced iron availability, heme synthesis, or globin production  Normocytic ( 80 < MCV < 100)  Anemia of chronic disease  Macrocytic (MCV > 100)  Liver disease, B12, folate

Step 2  Step 2-Identify Morphologies on Peripheral Smear  Examples:  Microcytosis, anisocytosis = Iron deficiency  Spherocytes = hereditary spherocytosis, warm AIHA  Macrocytes = B12 or folate def, myelodysplasia  Target cells = Hgb-opathy, liver dz, splenectomy  Schistocytes = microangiopathy (TTP/HUS, DIC)  Nucleated erythrocytes = hemolysis/hypoxia  Teardrop cells = fibrosis/infiltration, BM granuloma  Bite cells = G6PD  Sickle cells = Sickle cell disease  Rouleaux = IgM myeloma (Waldenstrom)  Burr cell = kidney dz (uremia), spur cell = severe liver dz

Step 3  Step 3- Calculate the Reticulocyte Index:  Reticulocyte = Immature RBC, suggests marrow response  Reticulocyte Index (RI) = ReticCount * 0.5(Hct/45)  In general, RI <2% with anemia suggests hypoproliferation

Step 4  Step 4: Iron studies, BM biopsy and other:  Iron Studies:  Iron Deficiency: Low Fe, high TIBC, low ferritin, low %sat  Inflammatory Anemia: nl/Low Fe, low TIBC, high ferritin  Other: Bone Marrow Biopsy (often the gold standard), EPO levels, Hgb electrophoresis, Coombs’ test, NADPH testing, etc.

Iron Deficiency Anemia  History: bleeding, pregnancy, malabsorption..  Step 1) Microcytosis  Step 2) Anisocytosis (high RDW)  Step 3) Low Retic Count  Step 4) low iron level, HIGH TIBC, low ferritin

Who needs a GI work-up?  All men, all women without menorrhagia, women greater than 50 with menorrhagia  If UGI symptoms, EGD  If asymptomatic, colonoscopy  Women less than 50 plus menorrhagia: consider GI workup based upon symptoms

Iron Studies in Iron Deficiency Finding Felow TIBCHigh % Satlow Ferritinlow

Treatment of Anemia  Treat the underlying cause  Oral Iron usually the correct answer  Consider co-existent iron deficiency as well  If underlying disease state requires it, consider EPO injection

Summary  Just approach it one step at a time!  Remember that in iron deficiency, iron is low, freeing up your binding capacity, giving a high TIBC  For all anemia, try and treat the underlying cause.

References  Harrison’s Principles of Internal Medicine  Adamson JW. Chapter 103. Iron Deficiency and Other Hypoproliferative Anemias. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; Accessed December 7, 2011  Wians, F.H. and Urban JE. “Discriminating between Anemia of Chronic disease Using Traditional Indices of Iron Status v. Transferring Receptor Concentration” American Journal of Clinical Pathology. Volume 115.  UptoDate  Schrier, SL. Approach to the adult patient with anemia. In: UpToDate, Landaw, SA(ED). UptoDate, Waltham, MA  Schrier, SL. Causes and diagnosis of anemia due to iron deficiency. In: UpToDate. Landaw, SA.(ED). Uptodate, Waltham, MA