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Anemia General Principles G6PD Deficiency Hemolytic and Aplastic Anemia Sickle Cell Anemia • Anemia Is a Sign, Not a Disease

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Anemia General Principles G6PD Deficiency Hemolytic and Aplastic Anemia Sickle Cell Anemia • Anemia Is a Sign, Not a Disease Anemias Vitamin B12 deficiency Folate deficiency Iron deficiency Anemia General Principles G6PD deficiency Hemolytic and aplastic anemia Sickle cell anemia • Anemia is a sign, not a disease. Thalassemia Coagulation Disorders • Anemia's are a dynamic process. Factor VIII disorders Factor IX disorders • It is never normal to be anemic. Factor XI disorders • Correct use of lab tests is paramount. Thrombocytopenia HEMATOLOGY for Board Review Idiopathic thrombocytopenic purpura • Concomitant causes of anemia are common. Thrombotic thrombocytopenic purpura Joe Schwenkler, MD Von Willebrand's disease • The diagnosis of iron deficiency anemia Medical Director Malignancies mandates further work‐up. UMDNJ‐ PA Program Acute/chronic lymphocytic leukemia June 7, 2013 Acute/chronic myelogenous leukema Lymphoma This image is a work of the National Institutes of Health Multiple myeloma MORPHOLOGIC APPROACH TO ANEMIA RBC Destruction/ Life Cycle • Microcytic Anemia‐> MCV<80 Reticulocyte Count – Reduced iron availability —severe iron deficiency, the anemia of chronic disease, copper deficiency • Normal life span about 120 days • Erythrocytes newly released from Bone Marrow • Destroyed by phagocytes – Reduced heme synthesis —lead poisoning, • Contain small amount of RNA congenital or acquired sideroblastic anemia – spleen, liver, bone marrow, lymph nodes – Reduced globin production — thalassemic states, • hemeÆ biliverdin Æ unconjugated (indirect) • Stain with methylene blue other hemoglobinopathies bilirubin • Increase in response to erythropoietin (EPO) • Macrocytic Anemia‐> MCV>100 • liver converts to conjugated (direct) bilirubin which – Megaloblastic anemias‐ Folic acid and Vitamin B12 enhances elimination from the body deficiency • globin and iron Æ recycled – alcohol abuse, liver disease, and hypothyroidism • RBC destruction in blood vessels Æ free Hb in http://en.wikipedia.org/wiki/Image:Hematopoiesis_%28human%29_diagram.png • Normocytic Anemia urine (Hemoglobinuria vs. Hematuria which is whole red blood cells in urine due to kidney or – Anemia of chronic disease tissue damage) – Anemia of chronic renal failure KINETIC APPROACH TO ANEMIA Algorithm using Retic. count, WBC, Platelet IRON METABOLISM Decreased Production (Low Retic count) Low Retic count suggests poorly functioning Lack of nutrients…iron, Vitamin B12, Folate bone marrow Bone Marrow Suppression… Aplastic anemia Normal Platelets and WBC • Serum iron is free Low levels of trophic factors…chronic renal disease Acute blood loss • Transferrin binds iron in circulation (low EPO), low thyroid, testosterone Renal disease Anemia of chronic disease Infections – TIBC is identical Increased destruction (High Retic count) Drugs – % Saturation is serum iron/TIBC Hemolytic Anemias Low platelets and WBC • Ferritin stores iron in liver and Reticulo Inherited…sickle cell, thalassemias Leukemia Acquired…idiopathic, drug‐induced, and myelodysplastic Endothelial System (RES) syndrome. Aplastic anemia Infection Case One 76 yo female comes in c/o being “run down” for over a month Only med is daily ibuprofen for chronic LBP PMH unremarkable, no previous hosp. Denies extra stress, problems sleeping except for restless legs Recently has been craving ice to chew (Pagophagia) Physical exam unremarkable except angular stomatitis, glossitis, pale conjunctiva, 2/6 SEM at LUSB, and spoon nails as below Angular Stomatitis (Cheilosis) (from (From wikipedia commons) wikipedia commons) LAB RESULTS What is your next step? • Hgb 8.2 (12.3 – 15.3), Hct 27.4 (36 – 44) 1. Bone marrow • MCV 80.8 (80‐100) 2. Rx with vitamin B12 • RDW (12.7‐14.5) 14.6‐ Anisocytosis 3. Transfuse 2 units • Retic count (1.1‐2.1) 1.6 packed cells • Serum ferritin 11.2 (40‐200) 4. GI work‐up for • Serum iron 28.6 (30‐160) occult bleeding • TIBC (transferrin level) 376 (230‐400) Spoon nail (from wikepedia commons) 5. Treat with EPO • Transferrin saturation 10.2 (9.6‐29) Etiology of Iron deficiency Anemia What is your next step? Signs of iron deficiency anemia • Increased Requirements 1. Bone marrow • Microcytic anemia causing spoon nails – Bleeding from some GI source 74% – Menses 2. Rx with vitamin B12 (koilonychia). • Glossitis – Blood donation (one unit= 250mg iron) 3. Transfuse 2 units • esophageal web formation (dysphagia – Growth periods, pregnancy, lactation packed cells due to Plummer‐Vinson syndrome). – Infants fed cow’s milk suffer from reduced • Restless legs is often associated anemia, bioavailability iron and induced GI bleeding 4. GI work‐up for • Inadequate supply occult bleeding check ferritin! • Pica is unique to iron‐deficiency • Intestinal malabsorption‐ iron absorbed in duodenum 5. Treat with EPO syndrome. • Sprue, celiac, atrophic gastritis 7% 9% 7% • Gastric surgery bypassing duodenum (Rx high doses) 2% • Calcium inhibits GI absorption 12345 Fe deficiency Fe deficiency Severe Fe Normal without with mild deficiency with Treatment anemia anemia severe anemia Case Two Marrow iron 2+ to 3+ None None None • Ferrous sulfate 325mg b.i.d. Serum iron 60 to 150 60 to 150 <60 <40 47 yo male with 10 year h/o type 2 comes for PE – Beware constipation Iron binding Currently taking max doses metformin & glyburide capacity 300 to 360 300 to 390 350 to 400 >410 • Recheck blood tests 6 weeks later (transferrin) BP 148/92, retinal exam shows cotton wool exudates Saturation Diminished monofilament sensation on feet – Continue oral iron until serum ferritin normalizes (SI/TIBC), 20 to 50 30 <15 <10 Diabetes poorly controlled with A1c=10.6% (up to 6 months) percent Hemoglobin Normal Normal 9 to 12 6 to 7 Microalbumin 300 (<20), creatinine 1.4 Normal or Hypochromia • Iron salts not absorbed well if taken with food Red cell CBC shows Hgb 9.1, MCV 85, normal platelets Normal Normal slight and morphology • Iron pills need to be given 2 hours before, or hypochromia microcytosis Stool guiac negative x 3 Plasma or Serum ferritin 170 (40‐200), Retic count .5% four hours after antacids 40 to 200 <40 <20 <10 serum ferritin Serum iron 65 (60‐150), TIBC 320 (300‐360) Nail and • Vitamin C helps absorption Other tissue None None None epithelial changes changes What can cause elevated ferritin AND What can cause elevated ferritin AND What is the best treatment for this low serum iron low serum iron patient? 78% 1. Chronic inflammation 1. Chronic inflammation 1. EPO 2. Aplastic anemia 2. Aplastic anemia 2. Transfuse 2 units pc 3. Hemolysis 3. Hemolysis 3. Oral iron 4. Hemoglobinopathies 4. Hemoglobinopathies 4. Parenteral iron 5. Acute leukemia 5. Acute leukemia 7% 9% 7% 0% 12345 Diagnosis of Anemia of Chronic Disease is often complicated… ANEMIA OF CHRONIC DISEASE (ACD) What is the best treatment for this chronic iron (ANEMIA OF INFLAMMATION) patient? disease deficiency Second most common anemia after Iron serum iron 64% Deficiency 1. EPO Induced by inflammatory cytokines (IL‐6) 2. Transfuse 2 units pc Reduction in red blood cell (RBC) production by TIBC BM (transferrin) 3. Oral iron Trapping of iron in macrophages 4. Parenteral iron reduced plasma iron levels making iron relatively iron 23% unavailable for new hemoglobin synthesis saturation Erythroid precursors are impaired 9% serum nL or 5% Interferons are potent inhibitors Blunted erythropoietin response ferritin 1234 ACUTE VARIANT Underlying causes of ACD DIAGNOSIS OF ANEMIA CHRONIC ANEMIA OF CRITICAL ILLNESS ( ) Acute and chronic infections DISEASE • Acute event‐related anemia TB Generally mild/moderate anemia (Hb 8‐10) – after surgery, major trauma, myocardial Endocarditis Normochromic, normocytic (may be slightly low) infarction, or sepsis Chronic UTI Low to normal reticulocyte count Malignancies • Secondary to tissue damage and acute Reduced serum iron and transferrin saturation Metastatic cancer inflammatory changes Leukemia Reduced or normal TIBC/transferrin levels • Shares many of the features of ACD Lymphoma Normal ferritin levels (acute phase reactant) – low serum iron Chronic arthritic conditions Need to exclude chronic renal failure, – high ferritin Chronic renal insufficiency hyperthyroidism, hypothyroidism – blunted response to EPO Hypothyroidism May have concomitant iron deficiency anemia ANY CHRONIC INFLAMMATORY CONDITION! TREATMENT OF ACD HEMOGLOBINOPATHIES Normal Adult Hemoglobins Sickle cell disease‐ homozygous Erythropoietin (EPO) is most effective therapy Autosomal recessive disease Name of Substitution of the amino acid valine for glutamine Hemoglobin Distribution Structure Oral iron of little benefit unless also iron 8% to 10% of African Americans carry gene A 95%‐98% of adult Hb α β deficient Sickle cell trait‐ heterozygotes 2 2 Transfusions only for short‐term if Hb<8 Splenic infarction can occur with hypoxia (altitude) A2 1.5%‐3.5% of Adult Hb α2δ2 Renal hematuria common Who to treat with EPO? F Fetal, 0.5%‐1.0% of α2γ2 Beware bacteruria during pregnancy adult Hb Hemoglobin <10 (pyelonephritis) Additional risk factors (pulmonary, CV, renal) Thalassemias‐ imbalanced synthesis of normal What is goal of therapy? globin chains Beta Hb 11 to 12 generally accepted Alpha Pathophysiology of SCD SICKLE CELL ANEMIA • Chronic hemolysis of sickle cell disease is usually • On deoxygenation, hemoglobin associated with: S polymers form, causing cell – a mild to moderate anemia (hematocrit 20 to 30 sickling and damage to the percent) membrane – reticulocytosis of 3 to 15 percent (accounting for • Vasocclusive episodes result the high or high‐normal mean corpuscular volume [MCV]) from a combination of vascular
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