Approach to the Patient with Approach to the Patient with ANEMIAANEMIA

Lisa Mohr, MDLisa Mohr, MD

Mike Tuggy, MDMike Tuggy, MD

ObjectivesObjectives

Review basic science of the RBCReview basic science of the RBC

Define AnemiaDefine Anemia

Review key aspects of history, physical Review key aspects of history, physical and lab evaluationand lab evaluation

Review a systematic approach to the Review a systematic approach to the differential diagnosisdifferential diagnosis

Case-based application of clinical Case-based application of clinical conceptsconcepts

RBC-The important playersRBC-The important players

HemoglobinHemoglobin– reversibly binds and transports 02 from lungs reversibly binds and transports 02 from lungs

to tissuesto tissues– 4 globin chains & iron4 globin chains & iron

RBC-The important players (2)RBC-The important players (2)

IronIron– key element in the production of hemoglobinkey element in the production of hemoglobin– absorption is poorabsorption is poor

TransferrinTransferrin– iron transporteriron transporter

FerritinFerritin– iron binder, measure of iron stores, *also iron binder, measure of iron stores, *also

acute phase reactant*acute phase reactant*

DefinitionsDefinitions

Anemia-values of hemoglobin, hematocrit Anemia-values of hemoglobin, hematocrit or RBC counts which are more than 2 or RBC counts which are more than 2 standard deviations below the meanstandard deviations below the mean– HGB<13.5 g/dL (men)HGB<13.5 g/dL (men) <12 (women)<12 (women)– HCT<41% (men)HCT<41% (men) <36 (women)<36 (women)

CASECASE

ML is a 64-year old male who has not had ML is a 64-year old male who has not had any primary care for several years. When any primary care for several years. When he tried to give blood last week, he was he tried to give blood last week, he was told that he was anemic. He presents to told that he was anemic. He presents to your clinic for evaluation.your clinic for evaluation.

What would you do??What would you do??

Evaluation of the Patient Evaluation of the Patient

HISTORYHISTORY– Is the patient bleeding?Is the patient bleeding?

Actively? In past?Actively? In past?

– Is there evidence for increased RBC Is there evidence for increased RBC destruction?destruction?

– Is the bone marrow suppressed?Is the bone marrow suppressed?– Is the patient nutritionally deficient? Pica?Is the patient nutritionally deficient? Pica?– PMH including medication review, toxin PMH including medication review, toxin

exposureexposure

Evaluation of the Patient (2)Evaluation of the Patient (2)

REVIW OF SYMPTOMSREVIW OF SYMPTOMSDecreased oxygen delivery to tissuesDecreased oxygen delivery to tissues– Exertional dyspneaExertional dyspnea– Dyspnea at restDyspnea at rest– FatigueFatigue– Signs and symptoms of hyperdynamic stateSigns and symptoms of hyperdynamic state

Bounding pulsesBounding pulsesPalpitationsPalpitations

– Life threatening: heart failure, angina, myocardial infarctionLife threatening: heart failure, angina, myocardial infarction

HypovolemiaHypovolemia– Fatiguablitiy, postural dizziness, lethargy, hypotension, Fatiguablitiy, postural dizziness, lethargy, hypotension,

shock and deathshock and death

Evaluation of the Patient (3)Evaluation of the Patient (3)

PHYSICAL EXAMPHYSICAL EXAM••Stable or Unstable?Stable or Unstable?

-ABCs-ABCs-Vitals-Vitals

••PallorPallor••JaundiceJaundice

-hemolysis-hemolysis••LymphadenopathyLymphadenopathy••HepatosplenomegallyHepatosplenomegally••Bony PainBony Pain••PetechiaePetechiae••Rectal-? Occult bloodRectal-? Occult blood

Laboratory EvaluationLaboratory Evaluation

Initial TestingInitial Testing– CBC w/ differential (includes RBC indices)CBC w/ differential (includes RBC indices)– Reticulocyte countReticulocyte count– Peripheral blood smearPeripheral blood smear

Laboratory Evaluation (2)Laboratory Evaluation (2)

BleedingBleeding– Serial HCT or HGBSerial HCT or HGB

Iron DeficiencyIron Deficiency– Iron Studies Iron Studies

HemolysisHemolysis– Serum LDH, indirect bilirubin, haptoglobin, coombs, Serum LDH, indirect bilirubin, haptoglobin, coombs,

coagulation studiescoagulation studies

Bone Marrow ExaminationBone Marrow Examination

Others-directed by clinical indicationOthers-directed by clinical indication– hemoglobin electrophoresishemoglobin electrophoresis– B12/folate levelsB12/folate levels

Differential DiagnosisDifferential Diagnosis

Classification by Pathophysiology Classification by Pathophysiology – Blood LossBlood Loss– Decreased ProductionDecreased Production– Increased Destruction Increased Destruction

Classification by MorphologyClassification by Morphology– NormocyticNormocytic– MicrocyticMicrocytic– MacrocyticMacrocytic

Blood LossBlood Loss

AcuteAcute– TraumaticTraumatic– Variety of sourcesVariety of sources

Melena, hematemesis, menometrorrhagiaMelena, hematemesis, menometrorrhagia

ChronicChronic– Occult bleedingOccult bleeding

Colonic polyp/carcinonmaColonic polyp/carcinonma

Decreased ProductionDecreased Production

InfectiousInfectious

NeoplasticNeoplastic

EndocrineEndocrine

Nutritional DeficiencyNutritional Deficiency

Anemia of Chronic DiseaseAnemia of Chronic Disease

Decreased ProductionDecreased ProductionINFECTIOUSINFECTIOUS

BacterialBacterial– TuberculosisTuberculosis– MAIMAI

ViralViral– HIVHIV– ParvovirusParvovirus

Decreased ProductionDecreased ProductionNEOPLASTICNEOPLASTIC

LeukemiaLeukemia

Lymphoma/MyelomaLymphoma/Myeloma

Myeloproliferative SyndromesMyeloproliferative Syndromes

MyelodysplasiaMyelodysplasia

Decreased ProductionDecreased ProductionENDOCRINEENDOCRINE

Thyroid DysfunctionThyroid Dysfunction– HypothyroidismHypothyroidism

Erythropoietin DeficiencyErythropoietin Deficiency– Renal FailureRenal Failure

Decreased ProductionDecreased ProductionNUTRITIONAL DEFICIENCYNUTRITIONAL DEFICIENCYIronIron

B12B12

FolateFolate

Macrocytic AnemiaMacrocytic Anemia

MCV > 100MCV > 100

Megaloblastic:AbnormalitiMegaloblastic:Abnormalities in nucleic acid es in nucleic acid metabolismmetabolism– B12, FolateB12, Folate

Non-Non-megaloblastic:Abnormal megaloblastic:Abnormal RBC maturationRBC maturation– MyelodysplasiaMyelodysplasia

ETOH, liver dz, ETOH, liver dz, hypothryroidism, hypothryroidism, chemotherapy/drugschemotherapy/drugs

Microcytic AnemiaMicrocytic Anemia

MCV <80MCV <80

Reduced iron Reduced iron availabilityavailability

Reduced heme Reduced heme synthesissynthesis

Reduced globin Reduced globin productionproduction

Microcytic AnemiaMicrocytic AnemiaREDUCED IRON AVAILABILTYREDUCED IRON AVAILABILTYIron DeficiencyIron Deficiency– Deficient Diet/AbsorptionDeficient Diet/Absorption– Increased RequirementsIncreased Requirements– Blood LossBlood Loss– Iron SequestrationIron Sequestration

Anemia of Chronic DiseaseAnemia of Chronic Disease– Low serum iron, low TIBC, normal serum ferritinLow serum iron, low TIBC, normal serum ferritin– MANY!! MANY!!

Chronic infection, inflammation, cancer, liver diseaseChronic infection, inflammation, cancer, liver disease

Microcytic AnemiaMicrocytic AnemiaREDUCED HEME SYNTHESISREDUCED HEME SYNTHESIS

Lead poisoningLead poisoning

Acquired or Acquired or congenital congenital sideroblastic anemiasideroblastic anemia

Characteristic smear Characteristic smear finding: Basophylic finding: Basophylic stipplingstippling

Microcytic AnemiaMicrocytic AnemiaREDUCED GLOBIN PRODUCTIONREDUCED GLOBIN PRODUCTION

ThalassemiasThalassemias

Smear CharacteristicsSmear Characteristics– HypochromiaHypochromia– MicrocytosisMicrocytosis– Target CellsTarget Cells– Tear DropsTear Drops

Lab tests of iron deficiency of Lab tests of iron deficiency of increased severityincreased severity

NORMALNORMAL Fe deficiencyFe deficiency

Without anemiaWithout anemia

Fe deficiency Fe deficiency

With mild anemiaWith mild anemia

Fe deficiency Fe deficiency

With severe With severe anemiaanemia

Serum IronSerum Iron 60-15060-150 60-15060-150 <60<60 <40<40

Iron Binding Iron Binding CapacityCapacity

300-360300-360 300-390300-390 350-400350-400 >410>410

SaturationSaturation 20-5020-50 3030 <15<15 <10<10

HemoglobinHemoglobin NormalNormal NormalNormal 9-129-12 6-76-7

Serum FerritinSerum Ferritin 40-20040-200 <20<20 <10<10 0-100-10

Differential Diagnosis-RevisitedDifferential Diagnosis-Revisited

Classification by Pathophysiology Classification by Pathophysiology – Blood LossBlood Loss– Decreased ProductionDecreased Production– Increased Destruction Increased Destruction

INCREASED DESTRUCTIONINCREASED DESTRUCTION

Immune MediatedImmune Mediated

Non-immune MediatedNon-immune Mediated

Increased DestructionIncreased DestructionIMMUNE MEDIATEDIMMUNE MEDIATED

Cold AgglutininCold Agglutinin– Paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria– Post mycoplasmal hemolytic anemiaPost mycoplasmal hemolytic anemia

Warm AgglutininWarm Agglutinin– Drug inducedDrug induced– Autoimmune hemolytic anemiaAutoimmune hemolytic anemia– Transfusion reactionTransfusion reaction

Increased DestructionIncreased DestructionNON-IMMUNE MEDIATEDNON-IMMUNE MEDIATED

Extra-corpuscularExtra-corpuscular– Macro-circulatoryMacro-circulatory

HypersplenismHypersplenismExtracorporeal circulationExtracorporeal circulation

– Micro-circulatoryMicro-circulatoryDICDICTTPTTPHUSHUS

Intra-corpuscularIntra-corpuscular– RBC Wall (membrane or enzyme defects)RBC Wall (membrane or enzyme defects)– Heme or globin abnormalities (HbS, C)Heme or globin abnormalities (HbS, C)

Back to M.L.-Back to M.L.-You appropriately You appropriately decide to obtain more history!decide to obtain more history!

HPI: “I’ve been a little more tired than usual, but I’ve HPI: “I’ve been a little more tired than usual, but I’ve been busy at work. I’m getting close to retirement. been busy at work. I’m getting close to retirement. Nothing else is unusual. I avoid doctors if I can”Nothing else is unusual. I avoid doctors if I can”

PMH: Inguinal hernia repair 20 yrs agoPMH: Inguinal hernia repair 20 yrs ago

FH: F & MGF-heart attack(age 80), brother-alcoholismFH: F & MGF-heart attack(age 80), brother-alcoholism

SH: Married x44yr, smokes 1ppd, “a couple beers/night”SH: Married x44yr, smokes 1ppd, “a couple beers/night”

MEDS: daily multivitaminMEDS: daily multivitamin

ALLERGIES: noneALLERGIES: none

ROS:+fatigue, +urine seems a little darker latelyROS:+fatigue, +urine seems a little darker lately

More on M.L.More on M.L.

P.E. findingsP.E. findings– T 98.4 HR 98 Resp 20 BP 112/70T 98.4 HR 98 Resp 20 BP 112/70– Gen: NAD, appears younger than stated ageGen: NAD, appears younger than stated age– HEENT: skin and conjunctiva slightly paleHEENT: skin and conjunctiva slightly pale– NECK: no adenopathy or thyromegallyNECK: no adenopathy or thyromegally– Chest: CTABChest: CTAB– CV: RRR, no murmurCV: RRR, no murmur– ABD: no HSM, soft, normoactive bowel soundsABD: no HSM, soft, normoactive bowel sounds– GU: normal maleGU: normal male– Rectal: no masses, prostate smooth/not enlarged, Rectal: no masses, prostate smooth/not enlarged,

guaiac negative stoolguaiac negative stool

M.L.’s Initial LabsM.L.’s Initial Labs

Only a CBC w/ diff was obtained:Only a CBC w/ diff was obtained:– WBC: 8.2, HCT 32.2, MCV 79, Platelets 221, WBC: 8.2, HCT 32.2, MCV 79, Platelets 221,

differential - normaldifferential - normal

Initial Thoughts?Initial Thoughts?

Blood loss?Blood loss?– Age places him at risk for colon CAAge places him at risk for colon CA

Decreased Production?Decreased Production?– Alcohol use, Iron deficiencyAlcohol use, Iron deficiency

Increased Destruction?Increased Destruction?– ““Darker urine” latelyDarker urine” lately

Further Work-upFurther Work-up

CAGE questionsCAGE questionsPeripheral Blood SmearPeripheral Blood SmearReticulocyte countReticulocyte countIron StudiesIron Studies– FerritinFerritin– TIBCTIBC– % Saturation% Saturation

UrinalysisUrinalysisFOBT or colonoscopy referalFOBT or colonoscopy referal

More ResultsMore Results

CAGE screen reveals no positive responsesCAGE screen reveals no positive responsesSmear reveals microcytic, microchromic RBCsSmear reveals microcytic, microchromic RBCsRetic count is interpreted as “low”Retic count is interpreted as “low”Urinalysis negative for hemoglobinUrinalysis negative for hemoglobinFOBT: not completed by patientFOBT: not completed by patientIron StudiesIron Studies– Ferritin: 10Ferritin: 10– TIBC: 350TIBC: 350– % Sat: 15% Sat: 15

What’s next?What’s next?

Rule out Sources of BleedingRule out Sources of Bleeding– Counseling regarding colon CA and referral for Counseling regarding colon CA and referral for

colonoscopycolonoscopy

Consider oral iron therapyConsider oral iron therapyDietary counseling (iron sources, limiting etoh, Dietary counseling (iron sources, limiting etoh, etc)etc)Encourage follow-up for health care Encourage follow-up for health care maintenancemaintenance– Vaccinations (Tetnus/pneumovax)Vaccinations (Tetnus/pneumovax)– Other cancer screening Other cancer screening – Cholesterol ScreenCholesterol Screen

DiagnosisDiagnosis

Colonoscopy revealed Colonoscopy revealed small suspicious lesion in small suspicious lesion in sigmoid colon, pathology sigmoid colon, pathology revealing revealing adenocarcinoma. – adenocarcinoma. – Excised surgically, no Excised surgically, no mets.mets.Routine labs, one year Routine labs, one year later, reveal an HCT of later, reveal an HCT of 40%. He feels “better 40%. He feels “better than ever”!than ever”!

ReferencesReferences

Schrier, Stanley.Approach to the patient with Schrier, Stanley.Approach to the patient with anemia. Up to Date. 2004anemia. Up to Date. 2004Schrier, Stanley. Anemia of Chronic Disease. Up Schrier, Stanley. Anemia of Chronic Disease. Up to Date. 2004to Date. 2004Schrier, Stanley. Anemias due to decreased red Schrier, Stanley. Anemias due to decreased red Cell Production. Up to Date 2004Cell Production. Up to Date 2004Schrier, Stanley. Causes and diagnosis of Schrier, Stanley. Causes and diagnosis of anemia due to iron deficiency. Up to Date. 2004anemia due to iron deficiency. Up to Date. 2004Tierney, et al. Anemias. Current Medical Tierney, et al. Anemias. Current Medical Diagnosis and treatment. 2003. Pp469-489Diagnosis and treatment. 2003. Pp469-489