Diagnosis And Management Of Anemia In The Elderly
Diagnosis and Management of Anemia in the ElderlyDiagnosis and Management ofAnemia in the ElderlyBrian Koffman, MDCM, DCFP, DABFM, MS EdChief Medical Officer, CLL Society (CLLSociety.org)Retired Clinical ProfessorDepartment of Family MedicineKeck School of Medicine, USC Family PracticeLearning Objectives Differentiate among the etiological causes of anemia seenin geriatric patients Develop appropriate workup of elderly patients diagnosedwith symptomatic anemia or anemia detected by incidentalblood testing Incorporate strategies to manage elderly patients withanemia due to iron deficiency, nutritional deficiency orchronic disease, and determine when it is appropriate torefer to a hematologist or gastroenterologist for furtherevaluation1
Diagnosis and Management of Anemia in the ElderlyGeriatric Anemia Best Practices Anemia is not normal at any age A treatable cause can often be determined, that may improve quality oflife (QOL) Mean cell volume (MCV) is a free and helpful measure innarrowing differential diagnosis of geriatric anemia Microcytosis, MCV 80 fL Normocytosis, MCV 80-100 fL Macrocytosis, MCV 100 fL Unexplained macrocyctic anemia demands consideration ofa full work-up by a hematologistOver 65?98.1US Census Bureau Estimates of Population Aged 65 YearsPopulation, millions1009080Population aged 65years expected tomore than doublefrom 05020552060YearUS Census Bureau. Projections of the Population by Sex and Selected Age Groups for the United States: 2015 to 2060 (Table /tables/2014/2014-summary-tables/np2014-t3.xls.2
Diagnosis and Management of Anemia in the ElderlyIn 2018 The life expectancy of a 65-year-old US male is:19 years The life expectancy of a 65-year-old US female is:21 yearsSocial Security Administration. Life Tables for the US Social Security Area ncy.htmlIn 2018 The life expectancy of a 75-year-old US male is:12 years The life expectancy of a 75-year-old US female is:13 yearsSocial Security Administration. Life Tables for the US Social Security Area ncy.html3
Diagnosis and Management of Anemia in the ElderlyOver 85?According to US Census Bureau projections persons aged 85years are the fastest growing population segmentPersons aged 85 years19.7 million(4.7% of thepopulation)252015106.3 million(2.0% of thepopulation)5020152060US Census Bureau. Projections of the Population by Sex and Selected Age Groups for the United States: 2015 to 2060 (Table valence of AnemiaThe oldest old aged 85 yearsare both the fastest growingsegment of the population andhave the highest rates of anemia20% for women26% for menGuralnik JM, et al. Blood. 2004;104:2263-2268.Guralnik JM, et al. Hematology. 2005:528-532.4
Diagnosis and Management of Anemia in the ElderlyA “Normal” Hemoglobin is VariableLower Limits of Adult Hemoglobin (g/dL)WHO(1968)NHANES III(1994)*(20-59 years)NHANES III(1994)*( 60 years)Scripps-Kaiser(2006)*White men1313.812.813.7Black menNRS12.811.812.9White women12(11 if pregnant)12.212.012.2Black womenNRS11.311.311.5Population*5% threshold in Gaussian distributionNRS, not reported separatelyEthnic background, altitude of residence, smoking status, and physiologic fluctuations of plasma volume can influence hemoglobinWHO. World Health Organ Tech Rep Ser. 1968;405:5-37.Guralnik JM, et al. Blood. 2004;104:2263-2268.Beutler E, et al. Blood. 2006;107:1747-1750.Practical Take AwayThe cause of anemia in the elderly,even if mild, should be evaluated fortreatment to improve qualityand quantity of life5
Diagnosis and Management of Anemia in the ElderlyAnemia Development is Predictiveof Mortality in Older Persons During up to 16 years of the Cardiovascular Health Study (n 3,758)those who developed anemia or experienced a HGB decline (1.18per 1 g/dL decrease) over 3 years predicted subsequent mortality inboth men and women“Hemoglobin decreases identified a large group of elderlyindividuals at risk for subsequent adverse outcomes who wouldnot be identified using the WHO anemia criteria. These data mayallow clinicians to identify at-risk elderly individuals for earlyintervention to improve the quality and quantity of life”Zakai NA, et al. Am J Hematol. 2013;88:5-9.Risk Factors for Anemia or HGB DeclineThe following predicted anemia development over 3 years Baseline increasing age African-American Female Gender Diabetes Kidney disease predicted anemia development over 3 yearsZakai NA, et al. Am J Hematol. 2013;88:5-9.6
Diagnosis and Management of Anemia in the ElderlyAssociations with a LowHemoglobin in Older PersonsIncreasedDecreased Rates of recurrent falls Cognitive function Frailty index Mobility, bone density, skeletalmuscle mass Rates of major depression Risk of hospitalization and longerduration in hospital Outcomes in specific diseases(anemia as marker of disease severity) Congestive heart failure (poorerhemodynamics, more symptoms,higher mortality) Cancer (decreased survival) HIV infection, independent of viral loadSteensma DP, et al. Mayo Clin Proc. 2007;82:958-966.Differential Diagnosis of Geriatric AnemiaBetter Outcomes with TreatmentThe most helpful inexpensive tests for determining etiologyof anemia: Red blood indices: Mean cell volume (MCV) Red cell distribution width (RDW) Peripheral blood smear Reticulocyte count7
Diagnosis and Management of Anemia in the ElderlyAnemiaAnemia is not a disease itself, but a sign of a disease Many common causes Stepwise work-up can save time and resources A cause can usually be discovered and managedCauses of AnemiaInadequateRBC ProductionMarrow FailureLoss of RBCsPrematureRBC DestructionBleedingHemolysis(overt or occult)(intrinsic or extrinsic)NutritionalDeficiencyWolanskyj AP, et al. Hematology. In: Ficalora RD, ed. Mayo Clinic Internal Medicine Board Review. 10th ed. 2013;497-511.Anemia Differential Diagnosis by MCVMCV 80 fLMicrocytosisNormocytosisMacrocytosisIron deficiencyAnemia ofchronic diseaseB12 or folatedeficiencyThalassemiaAcute bleedingAlcohol abuseAnemia ofchronic diseaseRenal failure(low , MTX,chemoRx, etc)Hb CHb ERarer causesVit Cdef.MCV 100 fLLeadpoison.UnstableHbParaneoplasticEarly/mild irondeficiencyHemolysisMarrow disorders(esp. MDS)ReticulocytosisLiver disease orhypothyroidismArtifactHb, hemoglobinEPO, erythropoietinAZT, azathioprineMTX, methotrexateWolanskyj AP, et al. Hematology. In: Ficalora RD, ed. Mayo Clinic Internal Medicine Board Review. 10th ed. 2013;497-511.8
Diagnosis and Management of Anemia in the ElderlyRed Cell Distribution Width (RDW)𝑆𝐷 𝑜𝑓 𝑀𝐶𝑉𝑀𝐶𝑉 Anemia of chronicinflammation / renaldisease Acute blood loss orhemolysis Early iron, B12, or folatedeficiency Mixed anemia (eg, combinediron and B12 deficiency) Sickle cell disease Anemia of chronic disease Heterozygous thalassemia Hemoglobin E trait Iron deficiency β-thalassemia majorX 100MCV RDW HIGH RDW is the variation in RBC volume(reported as part of CBC) Aplastic anemia Chronic liver disease Antivirals / chemotherapy /alcoholNORMAL Included in CBC Normal RDW: 11% - 15% RDW useful in identifying anemia ofmixed causesLOW Elevated RDW ( 15%) knownas anisocytosisFolate / vitamin B12 deficiencyImmune hemolytic anemiaCytotoxic chemotherapyChronic liver diseaseMyelodysplastic syndromeNORMALSD, standard deviationELEVATEDRDWMarks PW, Glader B. Approach to Anemia in the Adult and Child. In: Hoffman F, et al. eds. Hematology Basic Principles and Practice. 5th. Philadelphia,PA: Churchill Livingstone/Elsevier;2009:439-446.Reticulocytes Immature RBCs (typically 1% of RBCs) containing ribosomal remnants thatcirculate in blood for about a day before fully developing into RBCs Marker of marrow RBC production activity Increase push of immature RBCs to compensate for severe loss of matureRBCs in conditions such as hemolytic anemia Reticulocytosis is simply elevated number of reticulocytes in the blood Abnormally low numbers indicate poor erythropoiesis in marrow May indicate anemia of chronic inflammation, aplastic anemia, pernicious anemia,bone marrow malignancies, abnormal erythropoietin, vitamin or iron deficiencies, orchemotherapyBrugnara C, et al. Curr Opin Hematol. 2013;20:222-230.9
Diagnosis and Management of Anemia in the Elderly75-year-old Female withRheumatoid Arthritis (RA) Receiving methotrexate and folate for RA Moderate RA changes in hand; otherwise normal examination Laboratory studies HGB 10.8 g/dL, MCV 75 fL, CBC otherwise normal Positive anticyclic citrullinated peptide (CCP) antibody, erythrocyte sedimentation rate (ESR)48 mm/hour Complete metabolic panel (CMP), including blood urea nitrogen (BUN) and creatinine WNL Normal serum iron, total iron binding capacity, and % saturation; ferritin 523 ng/mL (normalrange: 20-300 ng/mL) Stool negative for occult blood x 3; last colonoscopy 3 years ago was unremarkableFerritin Correlates RelativelyPoorly With Iron StoresMalesFemalesCorrelation between serum ferritin concentration and hepatic nonheme iron content as measured by the superconducting quantuminterference device (SQUID)Ferritin is a positive acute-phase reactant: Liver production rises in response to cytokine release into bloodstreamReproduced with permission from Canavese C, et al. Kidney Int. 2004;65:1091-1098.10
Diagnosis and Management of Anemia in the ElderlyPractical Take AwayFerritin level is NOT a reliable measure of ironstorage in the body, because it is a positive acutephase reactant and can rise with inflammationAnemia of Chronic Disease/Inflammation:The Most Common Form of Normocytic Anemia Most cases normocytic, some microcytic Hepcidin-mediated (high C-reactive protein elevated interleukin-6, a verysuggestive finding) Not associated with every disease – must be an inflammatory component Rheumatological conditions (eg, rheumatoid arthritis, lupus) Inflammatory bowel disease Cancer Chronic infections (eg, tuberculosis, osteomyelitis) Congestive heart failure (CHF), sometimesSteensma DP, et al. In: Ghosh AK, ed. Mayo Clinic Internal Medicine Board Review. 8th ed. 2009;409-472.11
Diagnosis and Management of Anemia in the Elderly65-year-old Male Truck Driver Seen for routine follow-up of type 2 diabetes,no complaints Early diabetic kidney disease Laboratory studies: Hemoglobin: 10.1 g/dL; MCV: 90 fL Fasting blood sugar: 151 mg/dL; HbA1c: 7.9% Urine microalbumin screen: 100 mg/g creatinine (normal, 30) BUN 46 mg/dL; creatinine 1.9 mg/dL; Estimated GFR:35 mL/min/1.73 m2 Vitamin B12 (510 ng/L) and RBC folate within normal range65-year-old Truck DriverCONTINUED Iron studies Serum ferritin: 98 ng/mL (normal range: 20-300 ng/mL) Serum iron: 110 mcg/dL (normal range: 60-170 mcg/dL) TIBC: 220mcg/dL (normal range: 240-450 mcg/dL) Transferrin saturation: 49% (normal range: 20%-50%)12
Diagnosis and Management of Anemia in the ElderlyCKD and Anemia Increased prevalence as renal function worsens Typically normocytic, normochromic, and hypoproliferative with low reticulocytes Low EPO is the predominant cause EPO production may be impaired out of proportion to changes in creatine clearance Also associated with disordered iron homeostasis Low serum transferrin saturation and normal to high serum ferritin with iron depletion in thebone marrow Elevated hepcidin levels impair dietary iron absorption and iron mobilization from body stores Severity can be reduced by correcting the iron deficiency with iron supplementation ESAs should be used after addressing all correctable causes of anemiaCKD chronic kidney disease; EPO erythropoietin; ESA, erythropoiesis-stimulating agentBabitt JL, et al. J Am Soc Nephrol. 2012;23:1631-1634.KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. http://www.kdigo.org/clinical practice guidelines/pdf/KDIGO-Anemia%20GL.pdfNeed to MapSerum EPO Level to HGB Level5000EPO, mIU/mL1000100101Inadequate EPO productionin response to anemia468101214HGB, g/dLGraphic shows the typical inverse relationship between erythropoietin levels and hemoglobin levels in anemia's not attributed to impaired erythropoietin production.Cazzola M, et al. Blood. 1997;89:4248-4267.Adapted with permission of American Society of Hematology from Use of Recombinant Human Erythropoietin Outside the Setting of Uremia, Cazzola,89(12) 1997; permission conveyed through Copyright Clearance Center, Inc.13
Diagnosis and Management of Anemia in the Elderly48-year-old School Teacher Diagnosed with Inflammatory Bowel Disease at age 22 Mild to moderate and have responded to treatment withtopical budesonide in conjunction with nutritional therapy Presents with increased fatigue No bruising, bleeding, numbness, tingling or ataxia Other medications: NSAIDs for knee pain Surveillance colonoscopy performed 2 years ago was negative Physical examination: Moderate pallor, some abdominal discomfort; otherwise unremarkable48-year-old School TeacherCONTINUED Complete blood count: Hemoglobin: 9.6 g/dL MCV: 74 fl Hematocrit, RBC counts, and mean corpuscular hemoglobinall below normal ranges Normal white blood count, differential and platelets Ferritin: 20 ng/mL (normal range, 20-300 ng/mL) Serum iron: 48 mcg/dL (normal range: 60-170 mcg/dL) Transferrin saturation 8% (normal range 20%-50%) Erythrocyte sedimentation rate, albumin and C-reactive-protein levels withinthe normal ranges A stool sample tested positive for occult blood14
Diagnosis and Management of Anemia in the ElderlyIron Deficiency Anemia (IDA) IDA is the predominant cause of microcytic anemia inthe US Most common causes of IDA: However up to 40% of patients with IDA are normocytic Heavy uterine bleeding (20%-30%) GI bleeding due to long-term use of aspirin/NSAIDS(10%-15%) Colorectal polyps/carcinoma (5%-10%) Dietary IDA is rare in the US, but may be seen invegetarians/vegans Plants contain non-heme iron, which is less wellabsorbed Total iron binding capacity (TIBC) Soluble transferrin receptor (sTfR) Diagnosis requires laboratory-confirmed evidence ofanemia, as well as evidence of low iron storesOnce diagnosed, the cause of IDA should beevaluatedIron is bound to transferrin in the plasmaTIBC is a direct measure of level of transferrinor the total capacity to bind ironTransferrin levels are increased in IDA andreduced in chronic inflammation Cell surface transferrin receptors internalizetransferrin resulting in intracellular releaseof ironExpression of transferrin receptors increase inthe absence of adequate iron storessTfR levels reflect iron stores and is notaffected by the inflammatory processIncreased levels of sTfR are also found inconditions of increased red cell turnoverShort MW, et al. Am Fam Physician. 2013;87:98-104; Camaschella C. N Engl J Med. 2015;372:1832-1843.Oral Iron Therapy Expect HGB increase of 1 g/dL after one month of treatment adequate response to treatmentand confirms the diagnosis Ferrous (Fe2 ) salts are preferred as they are better absorbed than ferric (Fe3 ) salts Reticulocytes should increase after 7 daysVitamin C may increases iron absorptionFormFormulationElemental IronTypical DosageFerrous fumarate324-mg tablet106 mgOne tablet twice per dayFerrous gluconate300-mg tablet38 mg1-3 tablets 2 or 3 times per dayFerrous sulfate325-mg tablet65 mgOne tablet 3 times per day Adherence can be a challenge due to GI adverse events (epigastric discomfort, nausea, diarrhea,and constipation) Eating more red meat is not enough (100 g ribeye steak 1.94 mg iron 254 kcal) Medications such as proton pump inhibitors may reduce absorption of dietary iron and iron tablets These effects may be reduced when iron is taken with meals, but absorption may decrease by 40% with foodShort MW, et al. Am Fam Physician. 2013;87:98-104.15
Diagnosis and Management of Anemia in the ElderlyIntravenous Iron Therapy Considered better tolerated and more effective than oral iron treatment in improving ferritin Can be used in patients who cannot tolerate/absorb oral iron, eg, those who have undergonegastrectomy, gastrojejunostomy, bariatric surgery, or other small bowel surgeries Old formulations of HMW iron dextran should be avoided due to reactions Used more frequently now due to better tolerance and fast response Iron deficient patients usually need 1000 – 1500 mg to repleteFormElemental IronTypical single doseLMW iron dextran (e.g. InFed ) – can give as total dose infusion50 mg/mLUp to TDISodium ferric gluconate (Nulecit )12.5 mg/mL62.5 or 125 mgIron sucrose (Venofer )20 mg/mL100 mgFerumoxytol (Feraheme )30 mg/mL510 mgFerric carboxymaltose (Injectafer )50 mg/mL750 mgLMW, low molecular weight; HMW, high molecular weight.Short MW, et al. Am Fam Physician. 2013;87:98-104; Rodgers GM, et al. J Am Soc Nephrol. 2008;19:833-840.Normocytic-Normochromic Anemias:Hemolytic Anemia lactate dehydrogenase (LDH) due to increased cell destruction, indirect bilirubin(increased HGB catabolism), haptoglobin, and sometimes reticulocyte count (bonemarrow regenerative effort if healthy marrow) DAT can further guide the work-up (but up to 10% of healthy people have DAT) Schistocytes (fragmented red blood cells)Schistocytes on peripheralblood smear?YesYesMicroangiopathichemolytic anemia(MAHA) associated withdefective valveValvularprosthesis?NoDAT TestNoEvaluate for disseminatedintravascular coagulation (DIC)or other microangiopathicprocess such as hemolyticuremic syndrome(HUS)/thromboticthrombocytopenic purpura(TTP)Modified from Tefferi A. Mayo Clin Proc. 2003;78:1274-1280.PositiveAutoimmune hemolyticanemia (AIHA)NegativeFlow cytometry forparoxysmal nocturnalhemoglobinuria (PNH)Osmotic fragility test toassess for spherocytesRBC enzyme analysis,HGB electrophoresis16
Diagnosis and Management of Anemia in the ElderlyMicrocytic-hypochromic Anemias:Thalassemia/Sickle Cell DiseaseConsider HGB analysis to identify possible hemoglobinopathies in patients from suspected ethnic groups with microcytic anemia, normal RDW and normal ferritinTesta-thalassemiab-thalassemiaSickle-cell diseaseFamily History /EthnicitySE Asian, Middle Eastern, Chinese, AfricanChinese, other Asians, African AmericansSub-Saharan Africa, Mediterranean basin,Middle Eastern, IndianHBG electrophoresis /HPLCAdults: normal† HbA2, HbA, and probably HbFHbS HbCGenetics (typicallyrecessive inheritance)Deletion of HBA1 and HBA2 genes onchromosome 16Mutations in the HBB gene on chromosome11 ( 170 known)Specific mutations in the 6th codon of HBBgene (HbS and or HbC)*Determinants of diseaseseverityNumber of affected alleles (1-4)Number of affected alleles (1-2) andmutation typeNumber of affected alleles (1-2), Hb variantand if thalassemia also presentTreatmentTrait: Asymptomatic Intermedia: Hemolysis which may needtransfusionsMajor: Usually embryonic / newborn lethalTrait: Asymptomatic Intermedia: transfusionsMajor: Lifelong transfusions, chelationTrait: Asymptomatic HbSS*: Transfusions to reduce HbS levels,chelation. L-glutamine, hydroxyurea forpainful venoocclusive crises, BMTHbSC*: Less severe than HBSSHPLC, high-performance liquid chromatography*HbS hemoglobin S (glu val substitution at codon 6); HbC hemoglobin C (glu lys substitution at codon 6); HbSC HbS/HbC compound heterozygote;HbSS homozygous for HbS†Newborns: may have HbH or Hb Bart’s Persons with trait are asymptomatic and require no treatment or long-term monitoring. They usually do not have IDA.Rund D, Rachmilewitz E. N Engl J Med. 2005;353:1135-1146. Piel FB, Weatherall DJ. N Engl J Med. 2014;371:1908-1916.Piel FB, et al. N Engl J Med. 2017;376:1561-1573.Evaluation of Microcytic-hypochromicAnemiasMCV LowRBC Count normalor CRP normalFerritin. 20RBC Count normalor CRP Ferritin
Diagnosis and Management of Anemia in the Elderly 2 Geriatric Anemia Best Practices Anemia is not normal at any age A treatable cause can often be determined, that may improve quality of life (QOL) Mean cell volume (MCV) is a free and helpful measure in narrowing differential diagnosis
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2 Your Guide to Anemia. Anemia. What Is Anemia? Anemia is a blood disorder. Blood is a vital liquid that lows through your veins and arteries. Your body contains about 5 to 6 quarts of blood, which are constantly being pumped throughout your body by your heart. Blood carries oxygen
Cooley's Anemia) - Blackfan-Diamond Anemia - Pure Red Cell Aplasia - Sickle Cell Disease Other Disorders of Blood Cell Proliferation Anemias Anemias are deficiencies or malformations of red cells. - severe Aplastic Anemia - Congenital Dyserythropoietic Anemia - Fanconi Anemia (Note: the first cord blood transplant in 1988 was for this disease)
Fanconi Anemia: Guidelines for Diagnosis and Management, Fourth Edition, is the result of a Consensus Conference held by the Fanconi Anemia Research Fund in Herndon, Va., April 5-6, 2013. It replaces earlier editions published in 1999, 2003, and 2008. These guidelines are published for physicians who
2 carrying capacity is decreased, but tissue oxygenation is pre-served. Anemia causes hemodynamic alterations. The combined effect of hypo-volemia and anemia often occur as a result of blood loss. Acute anemia thus may cause tissue hypoxia or anoxia through diminished cardiac output, resulting in stagnant hypoxia, and decreased o
Diketahuinya faktor-faktor yang berhubungan dengan kejadian anemia postpartum wilayah kerja Puskesmas Wates Kabupaten Kulon Progo tahun 2018. 2. Tujuan khusus a. Diketahuinya proporsi kejadian anemia postpartum. b. Diketahuinya kebermaknaan hubungan faktor anemia kehamilan dengan kejadian anemia postpartum. c
UW Pediatrics Outpatient Clinical Guidelines Sources: AAP Clinical Report—Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in Infants and Young Children (0 –3 Years of Age), 2010 Screening and Management of Anemia at HMC Pediatric Clinic, 2013 Screening for Iron Deficiency –
with API 650’s level of risk of tank failure. Likewise, the rules in the external pressure appendix will be consistent with the basic part of API 650 with regard to loading conditions and combinations. Thus, starting with a specified design external pressure, roof live or snow load, and wind pressure (or velocity), the total roof design pressure is calculated as the greater of DL (Lr or S .
