Approach To The Evalua4on And Management Of Anemia

Transcription

1 Objec4ves Approach To The Evalua4on And Management Of Anemia Usha Perepu, MD Assistant Professor Hematology/Oncology 9/29/15 Defini4on of anemia Review the causes of anemia Laboratory evalua4on of anemia Management What is Anemia? Reduc4on below normal in the mass of red blood cells in the circula4on Hemoglobin concentra4on, hematocrit, RBC count Men: HGB < 13 g/dl, HCT 40% Women: HGB < 12.0 g/dl, HCT 35% Anemia and Volume Status Hb and HCT are CONCENTRATIONS Therefore dependent upon plasma volume Acute bleeds not reflected for hrs Due to volume deficit being slowly repaired via movement of fluid from extravascular to intravascular space Anemic pa4ents who are dehydrated will not appear anemic Pregnant women expand RBCs 25% but plasma volume increases 50%, producing physiologic anemia Anemia: Special Cases Erythrocytosis People who live at high al4tude have greater RBC volume Smokers have increased HCT impairs the ability of the RBCs to deliver O2 African- American Hbs are 0.5 to 1.0g/dL lower than Caucasians Athletes (increased plasma volume, Fe deficiency, hemolysis, polycythemia, use of performance enhancing agents) Anemia and the Elderly Mul4ple studies show that the elderly do not have a lower normal range Anemia, while common in the elderly, is s4ll abnormal Hb < 13 in males and < 12 in females associated with an increased rela4ve risk of mortality (1.6 and 2.3 respec4vely) 1

2 Anemia: History Data from the Third National Health and Nutrition Examination Survey ( ) Prevalence of anemia rises rapidly after age 50, prevalence 20% over age 85 11% of men, 10.2% of women over 65 are anemic 1/3 due to nutritional deficiency, 1/3 to chronic inflammation or renal disease, 1/3 unexplained Most cases mild; only 2.8% of women and 1.6% of men had Hb < 11 g Ø Unexplained mild anemia in elderly people may simply be an effect of aging in some cases Is the pa4ent bleeding? NSAIDs, ASA Menstrual history, if applicable (include older women) Prior intes4nal surgery? Hx of hemorrhoids, hematochezia, or melena? Past medical history of anemia? Family history? Alcohol, nutri4onal ques4ons Liver, renal diseases Ethnicity Environmental/work toxins (ie lead) Blood 2004;104: Symptoms of Anemia Signs of Anemia Decreased O2 delivery Hypovolemia if acute loss Exer4onal dyspnea, fa4gue, palpita4ons, lightheadedness Severe: heart failure, angina Pica craving for clay or paper products Pagophagia craving for ice Tachycardia, tachypnea, orthostasis Pallor Jaundice Murmur Koilonychia or Spoon nails Splenomegaly, lymphadenopathy Petechiae, ecchymoses Atrophy of tongue papillae Heme + stool Red blood cell matura4on Kine4cs Of Erythropoiesis Hypoprolifera4ve (marrow not working well) Hyperprolifera4ve (marrow working) Calcula4ng the re4culocyte index will usually tell you which category your pa4ent is in 2

3 Re4culocytes Re4culocyte response Nucleated RBCs form in marrow where they mature for 3 days and then spend 1 day in circula4on (before maturing to RBC) Given avg life span of RBC of 100 days, 1% of RBCs are destroyed each day Re4cs form 1% of circula4ng RBCs qd Assess adequacy of bone marrow response to anemia Must adjust for the degree of anemia, use Re4culocyte Index RI = (measured re4c %) x (Hct/45) x (1/Correc4on Factor) CF: Hct >40 (1); (1.5); (2); <20 (2.5) Reflects increased circula4ng 4me for re4cs as Epo pushes them out of the marrow earlier RI < 2.0 indicates inadequate marrow response Causes of Anemia A kine%c approach, addressing the mechanism(s) responsible for the fall in hemoglobin concentra4on A morphologic approach categorizing anemias via altera4ons in red blood cell (RBC) size (i.e., mean corpuscular volume) and the re4culocyte response Decreased RBC produc4on hypoprolifera4ve anemia( RI low) Deficiency of iron, B12, folate Marrow is dysfunc4onal from myelodysplasia, tumor infiltra4on, aplas4c anemia, etc. Bone marrow is suppressed by chemotherapy or radia4on Low levels of erythropoie4n, thyroid hormone, or androgens Increased RBC destruc4on hyperprolifera4ve anemia (RI high) RBCs live about 100 days Acquired: autoimmune hemoly4c anemia, TTP- HUS, DIC, malaria Inherited: spherocytosis, sickle cell, thalassemia Blood loss Re4c count increase generally less striking than in hemolysis 1. Obvious vs occult 2. Iatrogenic: daily CBC, surgical, hemodialysis, excessive blood dona4on 3. Menstrual blood loss 3

4 Morphologic approach to anemia Microcy%c anemia ( MCV < 80 fl) Normocy%c anemia ( MCV fl) Macrocy%c anemia (MCV > 100 fl) Iron deficiency anemia Acute blood loss Alcohol abuse Thalassemic disorders/ hemoglobinopathies Anemia of inflamma4on/ chronic disease Sideroblas4c anemia ( congenital, lead, alcohol, drugs) Iron deficiency (early) Anemia of inflamma4on/ chronic disease Bone marrow suppression ( aplas4c anemia, pure red cell aplasia) Folate, B12 deficiency Hemoly4c anemia Bone marrow disorders such as MDS Copper deficiency Endocrine dysfunc4on Drugs (chemotherapy agents ) Combined deficiency Liver disease Other laboratory parameters RDW: - Red blood cell distribu4on width, measures the degree of varia4on of the red cell size - If elevated, suggests large variability in sizes of RBCs MCH: mean corpuscular Hb - Low values are seen in iron deficiency and thalassemia, while increased values occur in macrocytosis of any cause MCHC: mean corpuscular Hb conc - low values occur in condi4ons that cause low MCV and MCH - increased values occur in spherocytosis and hemoglobinopathies Are the other cell lines down? - if evidence of leukopenia: consider bone marrow suppression, hypersplenism, B12 deficiency - platelet count: if low may be bone marrow suppression, thrombo4c microangiopathy such as TTP/HUS - high platelet count: myeloprolifera4ve neoplasm, iron deficiency Blood smear RBC size, shape Polychromasia (young re4cs) RBC inclusions (nucleated rbc, Howell- Jolly bodies, etc) Rouleaux Abnormal/immature leukocytes Platelet number/morphology Normal Polychromasia Normal rbc Microcytosis, hypochromia Spur cell anemia (liver disease) Microangiopathic hemolytic anemia 4

5 Iron Deficiency Anemia Iron deficiency affects more than 2 billion people worldwide and iron deficiency anemia remains the top cause of anemia Blood loss or decreased absorp4on are the major causes of iron deficiency In determining iron status it is important to perform iron panel and ferri4n Normal Macrocytic/megaloblastic Low ferri4n is almost always due to iron deficiency Iron deficiency anemia- treatment Oral iron is inexpensive and effec4ve when taken as prescribed, it can be considered front line therapy Oral iron therapy may take upto 6 months to replete stores Gastrointes4nal side effects are extremely common and may result in poor adherence to therapy Iron prepara4ons for Intravenous use Total iron deficit = Body weight [kg] x (Target Hb Actual Hb) [g/l] x Iron stores [mg] 500 mg iron for iron stores is recommended if the body weight is above 35 kg. Anemia of Renal Insufficiency Unremarkable peripheral blood smear Inappropriately normal erythropoie4n level Anemia usually severe and symptoma4c when Cr > 3.0 Formula%on Dose per infusion standard Maximum per single infusion Iron sucrose ( venofer) mg 300 mg/ over 2 hrs Ferumoxytol (Feraheme) 510 mg over 1 min mg over min Ferric carboxymaltose ( Injectafer) mg over min mg over min Mild to moderate anemia found in Cr Tx: Epogen or similar, Fe (oral, IV) if iron stores are found to be low 5

6 Anemia of Chronic Disease Folate and B12 Thought to be a cytokine mediated process which inhibits red blood cell produc4on or interferes with ac4on of erythropoie4n Therefore, the disease needs to be inflammatory Decreased iron u4liza4on/mobiliza4on Seen with rheumatologic diseases, chronic infec4ons, malignancy Indices: Low Fe, Low TIBC, N/increased Ferri4n May be seen in conjunc4on with Fe- deficiency Serum folate usually sufficient, but if folate level is normal but folate deficiency is suspected, check serum homocysteine (elevated because of impaired folate dependent conversion of homocysteine to methionine) or RBC- folate When B12 is slightly low a more sensi4ve and specific test is serum methylmalonic acid level, will be increased if B12 is truly low Evalua4on of Hemolysis Hemoly4c Anemia LDH: increases Indirect bilirubin increases (increased Hb catabolism) Haptoglobin decreases Re4culocyte count increases Urine hemosiderin test = present in intravascular, absent in extravascular hemolysis! Coombs test: (+) = immune (- ) non immune Immune Autoimmune hemoly4c anemia - Warm - Cold Alloimmune - Hemoly4c disease of newborn - Incompa4ble blood transfusion Drug Induced Non immune Microangiopathic hemoly4c anemia ( TTP, HUS) Trauma: prosthe4c valves, burns, exercise Infec4on: malaria RBC membrane defects Enzyme defects Hemoglobinopathy Paroxysmal nocturnal hemoglobinuria Indica4ons For Bone Marrow Biopsy Re4c index not appropriately increased No evidence of iron/b- 12/folate deficiency, renal failure, endocrinopathy, inflamma4on or other low EPO state Approach to Anemia CBC Reticulocyte count MCV RI < 2% RI > 2% Poor response to EPO, iron or vitamin replacement Underproduction Increased destruction or loss WBC/diff/ Plt abnormal, monoclonal gammopathy, or other peripheral blood evidence of marrow disorder Would you treat leukemia/mds or other neoplas4c disorder if you found it? MCV < 80 Microcytic MCV MCV Normocytic MCV > 100 Macrocytic Further work up Based on history, Physical, other 6

7 Anemia: Summary ANEMIA IS NEVER NORMAL Determine if ACUTE or CHRONIC Consider the e4ology CALCULATE the RETIC INDEX Look at the smear Consider the e4ology based on rbc morphology and laboratory studies Treat appropriately 7