Key Points. The mean corpuscular volume (MCV) and corrected reticulocyte count can divide all anemias into 6 simple categories. Anemia Classification

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1 Presenter Disclosure Information 7:45 8:45 am Evaluation of SPEAKER Andrew Eisenberger, MD The following relationships exist related to this presentation: Andrew Eisenberger, MD: No financial relationships to disclose. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Key Points A complete blood count with reticulocyte count can classify all anemias into six basic categories. History, review of systems and physical exam may help elucidate the cause of anemia. Additional laboratory testing can be tailored to the above findings. Distinction between iron deficiency anemia and anemia of chronic disease is essential. The mean corpuscular volume (MCV) and corrected reticulocyte count can divide all anemias into 6 simple categories. Microcytic, Microcytic, Classification MCV Low Normal High Normocytic, Normocytic, Macrocytic, Macrocytic, High Low/Normal Reticulocyte Count α/β-thalassemia*, hemoglobin SC disease, really rare stuff of chronic disease, iron deficiency, lead poisoning Classification MCV Low Normal High Sickling diseases, bleeding of chronic disease, renal disease, bone marrow infiltration Autoimmune hemolytic anemia, Coombs negative hemolysis Hypothyroidism, folate or vitamin B12 deficiency, medications, MDS, multiple myeloma High Low/Normal Reticulocyte Count

2 Reticulocyte Count Calculation Step 1: Multiply red blood cell count by % retics. Step 2: Correct reticulocyte count for degree of anemia. Reticulocyte Count Calculation Example: In a patient with Hct 27%, the RBC count is about 3,000,000. If reticulocytes are 4% of this population, then the reticulocyte count is 3,000,000 x 4% = 120,000. Hyperproliferative anemia, right? Reference range: Men: 33, ,000, Women: 25,000-75,000 Corrected Reticulocyte Count Hematocrit Duration in Cirulation 45% 1 day 35% 1.5 days 25% 2 days 15% 2.5 days Corrected Reticulocyte Count Example revisited: In a patient with Hct 27%, the RBC count is about 3,000,000. If reticulocytes are 4% of this population, then the reticulocyte count is 3,000,000 x 4% = 120,000. Reticulocytes spend about 2 days in circulation with this degree of anemia. Corrected reticulocyte count = 120,000/2 = 60,000, so this is. Microcytic Hyperproliferative Hemoglobin electrophoresis can be very helpful. Diagnoses β-thalassemia trait with elevated Hemoglobin A 2 (>4.0%). Unable to detect α-thalassemia directly. Confirms presence of variant hemoglobins such as HgbSC disease. Osmotic fragility test rarely helpful. Normocytic Hyperproliferative Step 1: Look for the bleeding

3 Normocytic Hyperproliferative Smears are also helpful, especially for rare structural disorders. Macrocytic Hyperproliferative Most commonly are acquired antibody mediated, hemolytic anemias. IgG-mediated May fix C3 complement Extravascular hemolysis IgM-mediated Usually fix complement Intra- and extravascular hemolysis Antibody-Mediated Hemolytic Treatment of Antibody-Mediated Hemolytic Warm Antibody Uncommon Often idiopathic Hepatitis C-associated Autoimmune and lymphoproliferative disease association Cold Antibody Rare Rarely idiopathic Mycoplasma-associated Lymphoproliferative disease association Treatment Warm Antibody Cold Antibody Corticosteroids Always Rarely Rituximab Second-line Often Plasmapheresis Never In emergency Splenectomy Second-line Never Underlying Disorder Always Always Macrocytic Hyperproliferative s: Coombs Negative Hemolysis Congenital Glucose 6-phosphate dehydrogenase deficiency Red blood cell disorders Wilsons disease Acquired Paravalvular leaks, malfunctioning grafts ECMO TTP (all types) Paroxysmal nocturnal hemoglobinuria Malaria Microcytic, anemia of Chronic Inflammation Iron deficiency Ferritin Normal/high Low Iron Low Low TIBC Low/Normal High Iron/TIBC Variable <<25% MCH/MCHC Normal Low

4 ACD is Cytokine-Mediated Inflammatory Process Infection Cancer Auto-immune disease Immune Response Interleukins Interferons TNF Why does a ferritin >100 normally exclude iron deficiency? Target-organ Suppression Liver Kidneys Gut Bone marrow Approach to Iron Deficiency Bleeding Menstrual Treat ACD by treating the underlying chronic disease. Establish cause GI Celiac disease CKD Malabsorption Autoimmune gastritis H. pylori infection Bariatric surgery Iron Deficiency Treatment Oral and IV forms are equally effective. Adherence to oral iron improved with: Bowel prophylaxis Iron fumarate or gluconate IV iron: Does not constipate Only tolerated form for some patients Guarantees adherence Parenteral Iron Formulations Iron dextran (InFed) Efficient high dose single day treatment Small risk of allergy and anaphylaxis Iron sucrose (Venofer) Treatment spaced over weeks Little risk of allergy Pregnancy Category B Ferumoxytol (Feraheme) Rapid infusion of intermediate doses of iron Little risk of allergy

5 ESAs for of Chronic Kidney Disease Do NOT improve survival MAY improve quality-of-life Require adequate iron stores (>25% saturation) Rare side effects include: Hypertension Stroke Venous thromboembolism May be safest when goal Hgb is 11 g/dl Macrocytic, anemia Hypothyroidism Folate or vitamin B12 deficiency Medications Ethanol MDS Multiple myeloma Liver disease/cirrhosis Dyslipidemia Do not treat until IF antibody is sent! Evaluation of Vitamin B 12 Deficiency Malabsorption? Autoimmune or Atrophic Gastritis, Bariatric Surgery Celiac Disease Metformin Strict Vegan? Oral Vitamin B 12 Parenteral B 12 Parenteral B 12, Celiac diet Consider changing medications Medications Causing Macrocytosis Ethanol AZT (nrtis) Methotrexate Hydroxyurea Azathioprine and 6-mercaptopurine Anti-epileptics Chemotherapy (especially antimetabolites) Key points: 1. Look at the MCV 2. Check and correct the retic count 3. Classify the anemia 4. Ask intelligent questions 5. Take a focused exam 6. Order relevant ancillary tests