Medicine 5th year, 5th & 6th lectures (Dr. Sabir)

Approach to the Patient with Approach to the Patient with ANEMIAANEMIA

Dr. SABIRDr. SABIR

DefinitionsDefinitions

Anemia-Anemia-

– 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)

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 of hemolysis?Is there evidence of hemolysis?– 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)

SYMPTOMS of anemia:SYMPTOMS of anemia:Decreased 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••Bone PainBone Pain••PetechiaePetechiae••Rectal bleeding? Occult Rectal bleeding? Occult bloodblood

Not pale conjunctiva

Pale conjunctiva

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: Megaloblastic: Abnormalities in nucleic Abnormalities in nucleic acid metabolismacid metabolism– B12, FolateB12, Folate

Non-megaloblastic: Non-megaloblastic: Abnormal RBC Abnormal RBC maturationmaturation– Myelodysplasia Alcohol, Myelodysplasia Alcohol,

liver dz, hypothryroidism, liver dz, 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: Basophilic finding: Basophilic stipplingstippling

Microcytic AnemiaMicrocytic AnemiaREDUCED GLOBIN PRODUCTIONREDUCED GLOBIN PRODUCTION

ThalassemiasThalassemias

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

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)

Reticulocyte countReticulocyte count

Retic count = % immature RBCRetic count = % immature RBC

Normal 0.5-1.5% (for non-anemic)Normal 0.5-1.5% (for non-anemic)

<1% Inadequate production <1% Inadequate production

>=1% Increased production (? adequacy)>=1% Increased production (? adequacy)

Reticulocyte CorrectionReticulocyte Correction

%Retic count frequently overestimates%Retic count frequently overestimates

Retic count should be compared to non-Retic count should be compared to non-anemic RBC count to assess adequacy of anemic RBC count to assess adequacy of responseresponse

Corrected Retic count = %Retic X HCT/45Corrected Retic count = %Retic X HCT/45

RBC morphologyRBC morphology

7-9 7-9 m with 1/3 central palorm with 1/3 central palor

Lifespan of 110-120 daysLifespan of 110-120 days

About the size of nucleus of normal About the size of nucleus of normal lymphocytelymphocyte

Poikilocytosis & AnisocytosisPoikilocytosis & Anisocytosis

Basophilic stipplingBasophilic stippling

Precipitated RNAPrecipitated RNA

lead or heavy lead or heavy metal poisoning metal poisoning

Alcohol abuseAlcohol abuse

Hemolytic anemiaHemolytic anemia

Burr cellsBurr cells

Altered lipid in cell Altered lipid in cell membranemembrane

artifactartifact

UremiaUremia

Renal failureRenal failure

gastric CAgastric CA

transfused old bloodtransfused old blood

Elliptocytes/ovalocytesElliptocytes/ovalocytes

Abnormal Abnormal cytoskeletal proteinscytoskeletal proteins

Hereditary Hereditary elliptocytosiselliptocytosis

Howell Jolly bodyHowell Jolly body

Nuclear remnant - Nuclear remnant - DNADNA

hemolytic anemiahemolytic anemia

absent or absent or hypofunction spleenhypofunction spleen

Heinz bodyHeinz body

Schistocyte/helmet cellsSchistocyte/helmet cells

Fragmented Fragmented (mechanical or (mechanical or phagocytosis)phagocytosis)

DICDIC

TTPTTP

HUSHUS

VasculitisVasculitis

prosthetic heart valveprosthetic heart valve

severe burnssevere burns

Sickle cellsSickle cells

Molecular Molecular aggregation of aggregation of Hgb-SHgb-S

SS, SC, S-thalSS, SC, S-thal

rarely S-traitrarely S-trait

NRBCNRBC

Common in newbornCommon in newborn

severe degree of severe degree of hemolysishemolysis

SpherocyteSpherocyte

Absent central Absent central palorpalor

look smallerlook smaller

Hereditary Hereditary spherocytosisspherocytosis

immune hemolytic immune hemolytic anemiaanemia

StomatocyteStomatocyte

Mouth likeMouth like

Membrane defectMembrane defect

Smear artifactSmear artifact

Hereditary Hereditary stomatocytosisstomatocytosis

Liver diseaseLiver disease

Target cellsTarget cells

Increased Increased redundancy of redundancy of membranemembrane

hemoglobinopathieshemoglobinopathies

thalassemiathalassemia

liver diseaseliver disease

Tear drop cellsTear drop cells

Distorted drop Distorted drop shapedshaped

Smear artifactSmear artifact

myelofibrosismyelofibrosis

promyeloblastic promyeloblastic leukemialeukemia

space occupying space occupying lesions of marrowlesions of marrow

Microcytic anemiaMicrocytic anemia

Get Iron panel- S Fe, TIBC, ferritinGet Iron panel- S Fe, TIBC, ferritin Iron def. anemia

dec inc dec

Siderobla -stic anemia

inc dec inc

Thalasse mia -mia

inc/nl dec/nl inc/nl

Chronic disease

dec dec inc