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HematologicDisorders:TheAnemias

HematologicDisorders:TheAnemias

DefinitionofAnemia
Adecreaseinhemoglobin(orhematocrit)levelfromanindividualsbaselinevalue.

Reductionintheredcellmassorthebloodhemoglobinconcentration
Hemoglobinlevellessthanthelowerrangevalueforage(Ingeneralnormalhemoglobinlevelsare12
g/dLlowerinwomenandAfricanAmericanmenthaninwhitemen)

ClassificationofAnemia:

Physiologicclassificationleadstotreatment
Morphologicclassificationleadstodiagnosis
Typesofdisorders
Typesofanemia
Disordersofredcellproduction
Hypochromicmicrocytic
Disordersofredcellmaturation
Macrocytic
Disordersofredcelldestruction
Normochromicnormocytic

History&Physical

Historicalfactorsinevaluatingpatientwithanemia
Age

Sex
Race
Diet
Neonatal
Infection
Hepatitisinducedaplasticanemia
Infectioninducedredcellaplasiaorhemolyticanemia

Inheritance
Diarrhea(SuspectsmallboweldiseasewithmalabsorptionoffolateorB12,suspectbloodloss)

FamilyHistory

Anemia
gallbladderdisease
jaundice
sicklecellorthalassemia
splenomegaly
bleedingtendencies

NutritionalHistory
Dietaryintakeofironsources,vitamins,milk,andmeat

drug/toxinexposures
bonemarrowfailure
chronicillness

24hourdietaryrecall
Historyofpica
Picaisaneatingdisordertypicallydefinedasthepersistenteatingofnonnutritivesubstancesforaperiodof
atleast1monthatanageinwhichthisbehaviorisdevelopmentallyinappropriate(eg,>1824mo).The
substancesincludesuchthingsasclay,dirt,sand,stones,pebbles,hair,lead,plastic,ice,paper,paintchips,
coal,chalk,wood,andplaster.

Reviewofsystems

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Jaundice
Extremitypain
Abdominalpain
Bloodloss
Weightloss

PhysicalExamination

Pallor
Jaundice
Petechiae
Fundalhemorrhages

HematologicDisorders:TheAnemias

Recentinfections
Drugexposures
Travel
Behavioralchanges
Pallor

Petechiae,ecchymoses
Adenopathy
GIandGUdisorders
ChangesinstoolindicatingGI
bleeding

Excessivebruising
Mucousmembranebleeding

Jointorextremitypain
Heartmurmursandsignsof
CHF
Hepatosplenomegaly
Congenitalanomalies

Lymphadenopathy
Frontalbossing

DiagnosisofAnemia

LaboratoryAssessment

Completebloodcount:
Hemoglobin,hematocrit,RBCcount
RBCindices(MCV,MCH,MCHC,RDW)
WBCcountanddifferential
Plateletcount

Redcellmorphology(descriptionofblood
smear)
Reticulocyteproductionindex
Serumiron,TIBC,serumferritin
Bonemarrowaspiration/biopsy

RBCIndices
LookatH&Hfirst,then

MCV(meancorpuscularvolume)
75100mcg3
Decreased:microcytic(Irondeficiency)
Increased:macrocytic(Folicaciddeficiency,VitaminB12deficiency)
Normal:normocytic

MCH(meancorpuscularhemoglobin)
2333pg/cell
Decreased:hypochromicanemia(Irondeficiency)
Normal:normochromic
Increased:hyperchromicorpolychromic(macrocyticanemiassuchasperniciousanemia)

RDW(RBCdistributionwidth)
Normal:11.514.5%
CalculatedfromtheMCVandtheRBCcount
Quantitativemeasureofanisocytosis(RBCsunequalinsize)
Assistsindistinguishingirondeficiencyanemiafromthalassemia
BothconditionshavelowMCV
IrondeficiencyanemiahashighRDW
ThalassemiahasanormalRDW
TheRDWmaybecomeabnormalbeforetheanemiaoccurs.
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HypochromicMicrocyticAnemia

Decreasediron,increasedTIBC,increasedFEPandnormalHgbelectrophoresisindicateirondeficiency
anemia
Iflabstudiescontinuetoshowirondeficiency,considermalabsorption,noncompliance,inadequatedose

NormalTIBCwithhighHgbAorHgbFindicateThalassemiaMinor

AnemiaClassification

Microcytic(MCVlow)
irondeficiencyanemia(late)
anemiaofchronicdisease(late)
leadtoxicity(rare)
sideroblasticanemia(asfromchronicalcoholism,leadpoisoning,preleukemicmyelodysplasia,
pyridoxine[B6]deficiency)

IronDeficiencyAnemia

MostprevalentnutritionaldisorderintheUnitedStates
Prominentinagegroupsexperiencingratesofrapidgrowth:
toddlers
adolescents
pregnantandlactatingwomen

Almostalwaysduetobloodloss
So:Teststoolsforoccultblood/GIreferral
Alsodueto:
dietaryinsufficiency
decreasedabsorptionduetogastricsurgeryorheavyantaciduse

Threestagesofirondeficiencyanemia
Stage1ferritinandhemosiderinstoresdepleted

Stage2serumirondecreased,ironbindingcapacityincreased
Stage3Hemoglobindecreased,irondeficiencyaffectshemesynthesis
Clinicalmanifestations
Thin/chubby

Historyofpica
Behavioralchanges
Pale
Tachycardia
Mildsystolicejectionmurmur

Treatment
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Ferroussulfate325mgPOtid
ContinueuntilHgbreturntonormal
Then36monthsofbiddosingtoreplenishferritinstores.
Initiatingtherapywithonceadaydosing(325mg)andgraduallytitratingupwardmayhelpminimizeGI
intolerance
Lowerdosesmaybeusedtodecreaseconstipation.

AddingvitaminCpotentiatesironabsorption
Reticulocytecount12aftertherapyifanemiaissevereorbonemarrowactivityisinquestion
ReassessHgbafter34weekstodocumentimprovement
Hgbshouldreturntonormalin68weeks
Therapyshouldcontinuewithbiddosinguntilferritinstoresarereplenished(36months).
FailureofHgbtorespondtotreatment:
misdiagnosisnoncompliance
malabsorptionunrelentingbloodloss

Refernonresponderstoaphysician.
MacrocyticAnemias

MCVhigh
B12deficiency
Folatedeficiency
chemotherapyandothermeds
liverdisease
myelodysplasia
thyroiddisease

Mostcommoncause:alcoholabuse
B12andfolatedeficiency=1/3ofallmacrocyticanemias.
Physicianconsultationiswarrantedinallcases.

VitaminB12Deficiency

Mostcommoncauseisperniciousanemia,achronic,progressive,macrocyticanemiacausedbyadeficiency
inintrinsicfactor(substancenecessaryforB12absorptionintheGItract).
Autoimmunedisease
mostcommoninwomenage3560ofNorthernorEasternEuropeanancestry

LesscommoncausesofB12deficiency:
gastricsurgery(gastrectomy,ilealresection)
Crohnsdisease
pancreaticinsufficiency
dietaryinsufficiency(uncommonfoundprimarilyinthosewhoconsumenoanimalordairyproducts)

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AssessmentofVitaminB12Deficiency

S:changeintaste,anorexia,mouthsoreness,N,bowelchanges,irritability,memorychanges,moodswings,
paresthesias
O:Neurologicabnormalitiesandglossitis

Labs:NormalorelevatedMCV,slightlyelevatedbilirubin,decreasedreticcount.
Schillingtestcanbeusedtodifferentiateperniciousanemiafromothercauses

Treatment
Initiatedwith100mcgofB12IMonadailybasisfor1week,thenweeklydosefor1month,thenamonthly
doseforlife
Firstfewdaysoftreatment:olderadultatriskforCHFandhypokalemia
WHY???

Mayhavetosupplementfolateandironstores.

FolicAcidDeficiency

Causes
Inadequateintake(commoninelderlyalcoholics)

chronicingestionofovercookedfoods
increasedbodyrequirements(malignancy,hemolyticanemia,severeexfoliativepsoriasis)
Medications(phenytoin,methotrexate,triamterene,trimethoprim)
Presentswithmacrocyticanemiaandlowserumfolatelevels.
B12shouldalwaysbeassessedinpresenceoffolatedeficiency
Folatereplacementwillmaskhematologicfindingsbutnotpreventneurologicalsequelaecausedby
coexistentB12deficiency
Treatunderlyingcauseandsupplementfolicacid(usually1mgPOqd)untilresolved.

NormocyticAnemias

MCVnormal
irondeficiencyanemia(early)
anemiaofchronicdisease(early)
hemolyticanemia
irondeficiency+B12deficiency
renalorthyroiddisease

AnemiaofChronicDisease(ACD)

Anemiaoftenaccompanieschronicinflammationormalignancydueto:
decreasedRBClongevity
decreasederythropoiesis

Maybecomehypochromicormicrocyticovertime
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RarelycausesdropofHgb<9orHct<25unlessaccompaniedbycoexistingpathology
IrondeficiencyfrequentlycoexistswithACD.
Labs:
Likeirondeficiency:serumironandtransferrinsaturationlow
Unlikeirondeficiency:ferritinisnormalorincreasedandTIBCislow

Causes
Autoimmunedisease

Chronicinfection(TB,HIV,endocarditis)
Malignancy
Liverdisease
Chronicrenalfailure

Treatment
Aimedatunderlyingdiseaseprocess.

IfHgb<9,Hct<25,lookforcoexistingpathology(B12,irondeficiency,multiplemyeloma)
Ifrenalfailure:erythropoietin,Vit.C,E,iron
Empirictrialofirontotreatanycoexistentirondeficiency

DisordersofRBCproduction
Examples
aplasticanemia
Anemiasecondarytomalignanciesand/orchronicdisease
Intervention
BloodreplacementwithpackedRBCtransfusions

DisordersofRBCmaturation
Examples
Irondeficiency
Leadpoisoning
Thalassemiasyndromes

Interventions
Irontherapy
Nutritionalcounseling
Promotecompliance
Leadremoval
Chelationtherapy
Geneticcounseling

DisordersofRBCdestruction
Examples
Sicklecellanemia

G6PDdeficiency
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Pyruvatekinasedeficiency
Hereditaryspherocytosis

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