Hematologic Changes in Pregnancy

4/12/2015 Hematologic changes in pregnancy
OfficialreprintfromUpToDate
www.uptodate.com2015UpToDate
Hematologicchangesinpregnancy
Author SectionEditor DeputyEditors

KennethABauer,MD CharlesJLockwood,MD, KristenEckler,MD,
MHCM FACOG
JenniferSTirnauer,MD
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Nov2015.|Thistopiclastupdated:Mar14,2014.
INTRODUCTIONNormalpregnancyischaracterizedbyprofoundchangesinalmosteveryorgansystemto
accommodatethedemandsofthefetoplacentalunit.Thehematologicsystemmustadaptinanumberof
ways,suchasprovisionofvitaminsandmineralsforfetalhematopoiesis(iron,vitaminB12,folicacid),which
canexacerbatematernalanemia,andpreparationforbleedingatdelivery,whichrequiresenhancedhemostatic
function.
Whilethesechangesfacilitatehealthypregnancy,theyalsoincreasetherisksofsomeconditions(eg,venous
thromboembolism).Inaddition,physiologicchangesinbloodcellcountsmustbedistinguishedfrompregnancy
complicationsthatrequirespecifictreatments.
Thistopicdiscussesphysiologicchangesinbloodcellsandhemostasisduringpregnancy.Hematologic
complicationsofpregnancyarediscussedinseparatetopicreviews.
OVERVIEWThemostsignificanthematologicalchangesduringpregnancyincludethefollowing(table1):
Physiologicanemia
Neutrophilia
Mildthrombocytopenia
Increasedprocoagulantfactors
Diminishedfibrinolysis
PLASMAVOLUMEPlasmavolumeincreasesby10to15percentat6to12weeksofgestation[13],
expandsrapidlyuntil30to34weeks,afterwhichthereisonlyamodestrise(figure1).Thetotalgainatterm
averages1100to1600mLandresultsinaplasmavolumeof4700to5200mL,30to50percentabovethat
foundinnonpregnantwomen[1,4].
Duringpregnancy,plasmareninactivitytendstobeincreasedandatrialnatriureticpeptidelevelsareslightly
reduced.Thissuggeststhattheriseinplasmavolumeisinresponsetoanunderfilledvascularsystemcaused
bysystemicvasodilatationandtheriseinvascularcapacitance.Ifexpansionofbloodvolumewastheinitial
event,renalandatrialvolumesensorswouldrespond,leadingtotheoppositehormonalprofile(lowplasma
reninactivity,elevatedatrialnatriureticpeptide)[5,6].Thishypothesisisalsosupportedbytheobservationthat
increasingsodiumintakedoesnotleadtofurthervolumeexpansion[7].
Postpartum,plasmavolumedecreasesimmediatelyafterdelivery,thenincreasesagaintwotofivedayslater,
possiblybecauseofariseinaldosteronesecretion,whichoccursatthistime.Plasmavolumethendecreases
itisstillelevatedby10to15percentabovenonpregnantlevelsatthreeweekspostpartum,butisusuallyat
normalnonpregnantlevelsatsixweekspostpartum.
REDBLOODCELLSRedbloodcell(RBC)massbeginstoincreaseat8to10weeksofgestationand
steadilyrisesby20to30percent(250to450mL)abovenonpregnantlevelsbytheendofpregnancyinwomen
takingironsupplements[4,811].Amongwomennotonironsupplements,theredcellmassmayonlyincrease
by15to20percent[12].RBClifespanisslightlydecreasedduringnormalpregnancy[13].
ThemajormediatorofincreasedRBCmassisanincreaseinlevelsoferythropoietin,whichstimulatesRBC
production.Erythropoietinlevelsincreaseby50percentinnormalpregnanciesandvaryaccordingtothe
presenceofpregnancycomplications[14].TheresultingincreasedRBCmasspartiallysupportsthehigher
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metabolicrequirementforoxygenduringpregnancy[15].
Inwomennottakingironsupplements,meancorpuscularvolume(MCV)decreasesduringpregnancyand
averages80to84fLinthethirdtrimester[16].However,MCVincreasesapproximately4fLinhealthy
pregnantwomenandthosewithonlymildirondeficiency[17].
LevelsofRBC2,3bisphosphoglycerate(2,3BPG,alsocalled2,3diphosphoglycerate[2,3DPG])remain
elevatedduringpregnancy,whichleadstoadecreaseinoxygenaffinityofmaternalRBCs(figure2)[18].This
loweroxygenaffinity,combinedwithlowpCO2ofthematernalbloodduetoincreasedminuteventilation,
facilitatestransportofoxygenacrosstheplacenta.
AnemiaHealthypregnancyisassociatedwithamodestdecreaseinhemoglobinlevels(ie,physiologicalor
dilutionalanemiaofpregnancy).Thisdecreaseisduetoagreaterexpansionofplasmavolumerelativetothe
increaseinRBCmass.ThegreatestdisproportionbetweentheratesatwhichplasmaandRBCsareaddedto
thematernalcirculationoccursduringthelatesecondtoearlythirdtrimester(lowesthemoglobinistypically
measuredat28to36weeks[16]).Nearertoterm,hemoglobinconcentrationincreasesduetocessationof
plasmaexpansionandcontinuingincreaseinhemoglobinmass(figure1).Conversely,theabsenceof
physiologicanemiaappearstobeariskfactorforstillbirth[19].
Determiningaprecisedefinitionofanemiainpregnantwomenisnotstraightforward,giventhepregnancy
associatedchangesinplasmavolumeandRBCmass,ethnicvariationbetweenwhiteandblackwomen,and
thefrequentuseofironsupplementationinpregnancy.
TheCentersforDiseaseControlandPrevention(CDC)hasdefinedanemiaashemoglobinlevelsofless
than11g/dL(hematocritlessthan33percent)inthefirstandthirdtrimestersandlessthan10.5g/dL
(hematocritlessthan32percent)inthesecondtrimester[20].Sincehemoglobinandhematocritlevels
arelowerinAfricanAmericanadults,theInstituteofMedicinerecommendsloweringthehemoglobincut
offlevelby0.8g/dLinthispopulation[21].
TheWorldHealthOrganization(WHO)definesanemiainpregnantwomenashemoglobin<110g/L(11
g/dL)orhematocrit<6.83mmol/Lor0.33L/L(33percent)[22].Severeanemiainpregnancyisdefinedas
hemoglobin<70g/L(7g/dL)andrequiresmedicaltreatment.Verysevereanaemiaisdefinedas
hemoglobin<40g/L(4g/dL)andisamedicalemergencyduetotheriskofcongestiveheartfailure.
Womenwithhemoglobinvaluesbelowtheselevelscanbeconsideredanemicandshouldundergoastandard
evaluation(eg,completebloodcount,reviewofperipheralsmear,reticulocytecount,serumFe/TIBC,and
ferritin)[23].Sixteento29percentofpregnantwomenintheUnitedStatesbecomeanemicinthethird
trimester[24].Iftheevaluationisnegative,ahemoglobinaslowas10g/dLcanbeattributedtophysiologic
anemiasinceawidevarietyoffactorsaffectsthenormallevelofhemoglobininaspecificindividual.(See
"Approachtotheadultpatientwithanemia"and"Causesanddiagnosisofirondeficiencyanemiaintheadult",
sectionon'Pregnancy'.)
Chronicsevereanemiaismostcommoninwomenindevelopingcountries.Maternalhemoglobinbelow6g/dL
hasbeenassociatedwithreducedamnioticfluidvolume,fetalcerebralvasodilation,andnonreassuringfetal
heartratepatterns[25].Increasedrisksofprematurity,spontaneousabortion,lowbirthweight,andfetaldeath
havealsobeenreported[26].Inaddition,severeanemia(hemoglobinlessthan7g/dL)increasestheriskof
maternalmortality[27].Thereisnoevidencethatmaternalanemiaincreasestheriskofcongenitalanomalies
inoffspring.
Chronicsevereanemiaisusuallyrelatedto(1)inadequateironstoresduetonutritionaldeficiencyandintestinal
helminthicinfections,(2)folatedeficiencyduetoinadequateintake,and(3)chronichemolyticstates,suchas
malaria.Ideally,severeanemiacouldbepreventedandpregnancyoutcomeimprovedwithnutritional
supplementationandinfectioncontrolmeasures[28,29].Asanexample,arandomizedtrialinruralChinafound
anironfolicacidsupplement(60mgironplus400mcgfolicacid)wasassociatedwithhighermaternal
hemoglobinlevels,fewerbirthsbefore34weeksofgestation,andfewerearlyneonataldeathsthanfolatealone
[29].However,40percentofwomenwerestillanemicinthethirdtrimester.Asimilartrialfoundthataniron
folicacidsupplementgiventopregnantNepalesewomeninanareawhereirondeficiencywascommon
appearedtobeassociatedwithimprovementinsomeaspectsofintellectualandmotorfunctioninoffspring
evaluatedatage7to9years[30].
Wheresafebloodtransfusionisavailable,itisprobablyprudenttotreatsevereanemiaaggressively,aswith
redcelltransfusion,iftherearesignssuggestiveoffetalhypoxemia[23].
Physiologicanemiaofpregnancyshouldresolvebysixweekspostpartumsinceplasmavolumehasreturned
tonormalbythattime.(See'Plasmavolume'above.)
IronrequirementsInatypicalsingletongestation,maternalironrequirementsaveragecloseto1000mg
overthecourseofpregnancy:approximately300mgforthefetusandplacentaandapproximately500mg,if
available,fortheexpansionofthematernalhemoglobinmass.Twohundredmilligramsisshedthroughthegut,
urine,andskin.Sincemostwomendonothaveadequateironstorestohandlethedemandsofpregnancy,iron
iscommonlyprescribedaspartofaprenatalmultivitaminorasaseparatesupplement.Ingeneral,women
takingironsupplementshaveameanhemoglobinconcentrationthatis1g/dLgreaterthanthatofwomennot
takingsupplements.Referencerangesforironindicesinpregnancyarelistedinthetable(table2).(See
"Nutritioninpregnancy",sectionon'Iron'.)
Adetaileddiscussiononthediagnosis,prevention,andmanagementofirondeficiencyanemiainpregnant
womencanbefoundseparately.(See"Causesanddiagnosisofirondeficiencyanemiaintheadult",section
on'Pregnancy'and"Causesanddiagnosisofirondeficiencyanemiaintheadult",sectionon'Prevention'and
"Treatmentoftheadultwithirondeficiencyanemia",sectionon'Pregnancy'.)
FolaterequirementsInnonpregnantindividuals,thedailyfolicacidrequirementis50to100mcg.The
increaseinRBCproductionduringpregnancynecessitatesanincreaseinthefolicacidrequirement,butthisis
morethanmetbytheincreaseddailyintake(400to800mcg)alreadyrecommendedforpreventionofneural
tubedefects.(See"Folicacidsupplementationinpregnancy"and"Nutritioninpregnancy".)
WHITEBLOODCELLSPregnancyisassociatedwithleukocytosis,primarilyrelatedtoincreased
circulationofneutrophils.Theneutrophilcountbeginstoincreaseinthesecondmonthofpregnancyand
plateausinthesecondorthirdtrimester,atwhichtimethetotalwhitebloodcellcountsrangefrom9000to
15,000cells/microL[31].Datafromtwoseriesreportedmeanwhitebloodcellcountsinlaboringpatientsof
10,000to16,000cells/microL,withanupperlevelashighas29,000cells/microL[32,33]themeancount
increasedlinearlywiththedurationofelapsedlabor[33].Thewhitebloodcellcountfallstothenormal
nonpregnantrangebythesixthdaypostpartum.
Normalpregnantwomencanhaveasmallnumberofmyelocytesormetamyelocytesintheperipheral
circulation.Somestudieshaveobservedanincreaseinthepercentofbandsaspregnancyadvances[3436].
Dohlebodies(bluestainingcytoplasmicinclusionsingranulocytes)areanormalfindinginpregnantwomen.
(See"Evaluationoftheperipheralbloodsmear",sectionon'Neutrophilseries'and"Evaluationoftheperipheral
bloodsmear",sectionon'Granulation'.)
Inhealthywomenwithnormalpregnancies,thereisnochangeintheabsolutelymphocytecountandno
significantchangesintherelativenumbersofTandBlymphocytes[37].Themonocytecountisgenerally
stable,thebasophilcountmayslightlydecreaseandtheeosinophilcountmayslightlyincrease.
PLATELETSANDCOAGULATIONSYSTEMHemostasisinvolvescomplexinteractionsbetweenthe
coagulationsystem(figure3),platelets,andthevascularendothelium.Thefibrinolyticsystemhasa
complementaryroleinpreventingexcessivecoagulation,viaremovaloffibrinandclotdissolution(table3and
figure4).Theseprocessesinteracttoensurethatthecirculatingbloodflowsfreelyinthevascularbedandthat
bleedingisquicklyarrestedfollowingtrauma.(See"Overviewofhemostasis".)
Inpregnancy,however,thedemandsonthehemostaticandfibrinolyticsystemschangeinordertoprevent
excessivehemorrhageduringplacentalseparation.Arelativehypercoagulablestatecomparedwithnon
pregnantindividualsiscausedbyamarkedincreaseinsomecoagulationfactors,reducedfibrinolysis,and
increasedplateletactivity.
Changesinvasculartonethatenhanceuteroplacentalbloodflowalsooccur.Thesechangesareduetoa
varietyoffactors(eg,nitricoxide,endothelin,reninangiotensin,estrogen,progesterone,prostacyclin).
PlateletsAlthoughplateletcountsremaininthenormalnonpregnantrangeinmostwomenduring
uncomplicatedpregnancies[38],meanplateletcountsofpregnantwomenmaybeslightlylowerthaninhealthy
nonpregnantwomen(table2)[39].Serialplateletcountsduringuncomplicatedpregnanciesmay[40]ormaynot
[41]decrease,butthemeanvaluesingroupsofwomendonotnecessarilyreflectchangesinindividualwomen
[42].
Milddecreasesinplateletcountoccurinabout5percentofpregnancies(ie,gestationalthrombocytopenia,
incidentalthrombocytopeniaofpregnancy).Gestationalthrombocytopeniaischaracterizedbymild
asymptomaticthrombocytopeniaoccurringinthethirdtrimesterinapatientwithoutanyhistoryof
thrombocytopenia(otherthaninapriorpregnancy).Itisnotassociatedwithmaternal,fetal,orneonatal
sequelaeandspontaneouslyresolvespostpartum[4345].Plateletcountsaretypically>70,000/microL,with
abouttwothirdsbeing130,000to150,000/microL.Diagnosisandmanagementofgestationalthrombocytopenia
arediscussedindetailseparately.(See"Thrombocytopeniainpregnancy",sectionon'Gestational
thrombocytopenia'.)
Itisimportanttodistinguishgestationalthrombocytopeniafromothercausesofthrombocytopenia,including
severepreeclampsia,hemolysiselevatedliverfunctiontestsandlowplatelets(HELLP)syndrome,thrombotic
thrombocytopenicpurpura(TTP),immunethrombocytopenia(ITP),antiphospholipidsyndrome,anddrug
inducedthrombocytopenia.Mostoftheseconditionsareassociatedwithmoreseverethrombocytopeniaand/or
otherhematologicchanges.Theseotherconditionsarediscussedindetailseparately.(See"Thrombocytopenia
inpregnancy".)
Theplateletcountbeginstorisesoonafterdeliveryandcontinuestoincreaseforthreetofourweeksbefore
returningtobaseline.Inonestudyof50presumablynormalpregnant/postpartumwomenfollowedwithserial
plateletcounts,themeanplateletcountpredeliveryand3,7,15,25,and42daysafterdeliverywas219,000
267,000349,000363,000279,000and254,000permicroL,respectively[46].
CoagulationandfibrinolysisNormalpregnancyisaprothromboticstate[4757].
Avarietyofchangesoccurinprocoagulantandanticoagulantpathways,whichonbalanceincreasecoagulation
potentialonabackgroundofreducedanticoagulationandfibrinolysis.
Thefollowingchangesoccurincirculatinglevelsofcoagulationfactors,inhibitors,andfibrinolyticmarkers
(table2):
ThephysiologicalanticoagulantproteinSdecreases(measuredastotalproteinS,freeproteinS,and
proteinSactivity).
Procoagulantfactorsfibrinogen,factorsII,VII,VIII,X,XII,andXIIIincreaseby20to200percent[57,58].
TheprohemostaticfactorvonWillebrandfactorincreases.
Activityoffibrinolyticinhibitorsincreases,includingthrombinactivatablefibrinolyticinhibitor(TAFI),
plasminogenactivatorinhibitor1(PAI1),andPAI2[59].PAI1levelsincreasemarkedlyderivedfromthe
placentaanddecidua.
Thrombincleavageproductsincrease,suggestingongoingcoagulation.Changesincludeincreasesin
fibrinDdimer,fibrinmonomers,andfibrinopeptidesAandB[6067].Productsoffibrinolysisalso
increase,includingplasminogenandtissuetypeplasminogenactivator[68].
Otheranticoagulantandprocoagulantproteins(eg,antithrombin,proteinC,factorVandfactorIX)remain
unchangedorincreaseslightly[57,69].
ResistancetoactivatedproteinC(abiochemicaltestusedtodiagnosetheprothromboticfactorVLeiden
mutation)increasesinthesecondandthirdtrimesterswhenevaluatedbyatestusingplasmathatisnot
factorVdeficienthowever,thistypeoffirstgenerationtestisrarelyperformedclinicallyandisprimarily
ofhistoricalinterest.(See"FactorVLeidenandactivatedproteinCresistance:Clinicalmanifestations
anddiagnosis",sectionon'Diagnostictesting'.)
Theneteffectofthesechangesistoincreasethetendencyforthrombusformationandextension,which,
alongwithmyometrialcontractionsandhighlevelsofdecidualtissuefactorexpression,protectthemother
fromexcessivebleedingatthetimeofplacentalseparationanddelivery.Thesechangesalsoincreasetherisk
ofvenousthromboembolismduringpregnancyandespeciallythepostpartumperiod.
Laboratorytestsofcoagulationarenotroutinelydone(orrequired)duringpregnancy.Inastudyof117normal
pregnantwomen,theactivatedpartialthromboplastintime(aPTT)remainedinthenormalrangeduring
pregnancy,butdecreasedslightlynearterm[70].Theprothrombintime(PT)shortenedinsome.(See"Clinical
useofcoagulationtests".)
TheDdimerlacksutilitytoevaluatethelikelihoodofvenousthromboembolismduringpregnancy,dueto
changesinthisparameterandalackofnormalreferencerangesduringpregnancy.(See"Pulmonaryembolism
inpregnancy:Epidemiology,pathogenesis,anddiagnosis",sectionon'Laboratorystudies'.)
Postpartum,normalizationofcoagulationparametersandfactorlevelsvariesdependingonthefactor,butall
shouldreturntobaselinebysixtoeightweeksafterdelivery[46].Hemostasisprobablyshouldnotbe
evaluatedearlierthanthreemonthsfollowingdeliveryandafterterminatinglactationtoexcludepregnancy
relatedeffects[57].
Theeffectsofacquiredandinheritedthrombophiliasonpregnancyoutcomearecontroversialandactiveareas
ofinvestigation.Theseeffectsarediscussedseparately.(See"Inheritedthrombophiliasinpregnancy".)
POSTPARTUMPregnancyrelatedhematologicalchangesreturntobaselinebysixtoeightweeksafter
delivery[46].Withinthisrange,therateandpatternofresolutionofpregnancyrelatedchangesofspecific
hematologicalparametersvaryandaredescribedaboveinthesectiononeachparameter.
SUMMARYANDRECOMMENDATIONS
Themajorhematologicalchangesduringpregnancyarephysiologicanemia,neutrophilia,mild
thrombocytopenia,increasedprocoagulantfactors,anddiminishedfibrinolysis(table1).(See'Introduction'
above.)
Plasmavolumeincreasesby10to15percentat6to12weeksofgestation,andthenexpandsrapidly
until30to34weeks,afterwhichthereisonlyamodestrise(figure1).(See'Plasmavolume'above.)
Redbloodcellmassbeginstoincreaseat8to10weeksofgestationandsteadilyrisesby20to30
percent(250to450mL)abovenonpregnantlevelsbytheendofpregnancy.Agreaterexpansionof
plasmavolumerelativetotheincreaseinhemoglobinmassanderythrocytevolumeisresponsibleforthe
modestfallinhemoglobinlevels(ie,physiologicalordilutionalanemiaofpregnancy)observedinhealthy
pregnantwomen.TheCentersforDiseaseControlandPrevention(CDC)hasdefinedanemiaas
hemoglobinlevelsoflessthan11g/dLinthefirstandthirdtrimestersandlessthan10.5g/dLinthe
secondtrimester.(See'Redbloodcells'above.)
Theneutrophilcountbeginstoincreaseinthesecondmonthofpregnancyandplateausinthesecondor
thirdtrimester,atwhichtimethetotalwhitebloodcellcountsrangefrom9000to15,000cells/microL.
Thereisnochangeintheabsolutelymphocytecount.(See'Whitebloodcells'above.)
Thecirculatinglevelsofseveralcoagulationfactorschangeduringpregnancy(table2),resultingina
relativeprothromboticstate.(See'Coagulationandfibrinolysis'above.)
Meanplateletcountsofpregnantwomenmaybeslightlylowerthaninhealthynonpregnantwomen,but
mostpregnantwomenhavenormalplateletcounts(table2).(See'Platelets'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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thromboembolismduringpregnancyandpuerperiuman11yearDanishpopulationbasedstudyof63,300
pregnancies.ActaObstetGynecolScand199877:170.
52. HellgrenM,BlombckM.Studiesonbloodcoagulationandfibrinolysisinpregnancy,duringdeliveryand
inthepuerperium.I.Normalcondition.GynecolObstetInvest198112:141.
53. StirlingY,WoolfL,NorthWR,etal.Haemostasisinnormalpregnancy.ThrombHaemost198452:176.
54. CompPC,ThurnauGR,WelshJ,EsmonCT.FunctionalandimmunologicproteinSlevelsare
decreasedduringpregnancy.Blood198668:881.
55. CummingAM,TaitRC,FildesS,etal.DevelopmentofresistancetoactivatedproteinCduring
pregnancy.BrJHaematol199590:725.
56. BremmeKA.Haemostaticchangesinpregnancy.BestPractResClinHaematol200316:153.
57. HellgrenM.Hemostasisduringnormalpregnancyandpuerperium.SeminThrombHemost200329:125.
58. EsmonCT.MoleculareventsthatcontroltheproteinCanticoagulantpathway.ThrombHaemost1993
70:29.
59. KuDH,ArkelYS,PaidasMP,LockwoodCJ.Circulatinglevelsofinflammatorycytokines(IL1betaand
TNFalpha),resistancetoactivatedproteinC,thrombinandfibringenerationinuncomplicated
pregnancies.ThrombHaemost200390:1074.
60. FrancalanciI,ComeglioP,AlessandrelloLiottaA,etal.Ddimerplasmalevelsduringnormalpregnancy
measuredbyspecificELISA.IntJClinLabRes199727:65.
61. SenentM,BellartJ,ZuazuJausoroI,etal.[Markersofhypercoagulabilityduringpregnancy:thrombin
antithrombinIIIcomplexesandDdimer].Sangre(Barc)199136:21.
62. vanWerschJW,UbachsJM.Bloodcoagulationandfibrinolysisduringnormalpregnancy.EurJClin
ChemClinBiochem199129:45.
63. MercelinaRoumansPE,UbachsJM,vanWerschJW.Coagulationandfibrinolysisinsmokingand
nonsmokingpregnantwomen.BrJObstetGynaecol1996103:789.
64. BremmeK,OstlundE,AlmqvistI,etal.Enhancedthrombingenerationandfibrinolyticactivityinnormal
pregnancyandthepuerperium.ObstetGynecol199280:132.
65. BellartJ,GilabertR,FontcubertaJ,etal.Fibrinolysischangesinnormalpregnancy.JPerinatMed1997
25:368.
66. ChablozP,ReberG,BoehlenF,etal.TAFIantigenandDdimerlevelsduringnormalpregnancyandat
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67. KlineJA,WilliamsGW,HernandezNinoJ.Ddimerconcentrationsinnormalpregnancy:newdiagnostic
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68. BonnarJ,McNicolGP,DouglasAS.Fibrinolyticenzymesystemandpregnancy.BrMedJ19693:387.
69. ClarkP,BrennandJ,ConkieJA,etal.ActivatedproteinCsensitivity,proteinC,proteinSand
coagulationinnormalpregnancy.ThrombHaemost199879:1166.
70. CernecaF,RicciG,SimeoneR,etal.Coagulationandfibrinolysischangesinnormalpregnancy.
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73:31.
Topic429Version15.0
GRAPHICS
Summaryofhematologicalchangesassociatedwithnormal
pregnancy
Plasmavolume Increases30to50percent
Redbloodcellmass Increases20to30percent
Hemoglobinconcentration Decreases
Redcelllifespan Slightlydecreased
Erythropoietin Increases
Meancorpuscularvolume(MCV) Increasesslightly
Plateletcount Nochangetoslightdecrease
Whitebloodcellcount Increases(neutrophilia)
Lymphocytecount Nochange
Monocytecount Nochange
Basophilcount Nochangetoslightdecrease
Eosinophilcount Nochangetoslightincrease
Prothrombintime Slightdecrease
Bleedingtime Nochange
TotalproteinSantigen,freeproteinSantigen, Decreases
proteinSactivity
ResistancetoactivatedproteinC Increases
Fibrinogen,factorsII,VII,VIII,X,XII,XIII Increases20to200percent
Antithrombin,proteinC,factorV,factorIX Nochangetoslightincrease
VonWillebrandfactor Increases
Thrombinactivatablefibrinolyticinhibitor Increases
(TAFI),PAI1,PAI2
Ddimer Increases
Graphic89214Version2.0
Totalbloodvolume,plasmavolumeandredcell
volumeinnormalpregnancy
DatafromShniderSM,LevinsonG.AnesthesiaforObstetrics,3rded,Williams
&Wilkins,Baltimore,p.8.
http://www.uptodate.com/contents/hematologicchangesinpregnancy?topicKey=OBGYN%2F429&elapsedTimeMs=2&source=search_result&s 10/27
Oxyhemoglobindissociationcurve
Depictedhereistheoxyhemoglobindissociationcurvefornormaladult
hemoglobin(HemoglobinA,solidline).Notethathemoglobinis50percent
saturatedwithoxygenatapartialpressureof27mmHg(ie,theP50is27
mmHg)andis100percentsaturatedataPaO 2 ofapproximately100
mmHg.Depictedherearecurvesthatare"leftshifted"(blueline,
representingincreasedoxygenaffinity)and"rightshifted"(redline,
decreasedoxygenaffinity).Theeffectofrightorleftshiftingofthecurve
ismostpronouncedatlowoxygenpartialpressures.Intheexamplesshown,
theleftshiftedcurvemeansthathemoglobincandeliverapproximately70
percentofitsattachedoxygenataPaO 2 of27mmHg.Incontrast,the
rightshiftedhemoglobincandeliveronlyabout35percentofitsattached
oxygenatthisPaO 2 .Ahighproportionoffetalhemoglobin,whichhashigh
oxygenaffinity,shiftsthiscurvetotheleftinnewborns.
Normalreferencerangesinpregnantwomen
Nonpregnant First Second Third

Referen
adult* trimester trimester trimester
Hematology
Erythropoietin 427 1225 867 14222 13

(units/L)
Ferritin (ng/mL) 10150 6130 2230 0116 18
Folate,redbloodcell 150450 137589 94828 109663 6,9,10

(ng/mL)
Folate,serum(ng/mL) 5.418.0 2.615.0 0.824.0 1.420.7 1,6,913
Haptoglobin(mg/mL) 25250 130+/43 115+/50 135+/65 93
Hemoglobin (g/dL) 1215.8 11.613.9 9.714.8 9.515.0 2,3,6,7,
Hematocrit (percent) 35.444.4 31.041.0 30.039.0 28.040.0 1,2,5,6,

15
Iron,totalbinding 251406 278403 Notreported 359609 7

capacity (mcg/dL)
Iron,serum (mcg/dL) 41141 72143 44178 30193 2,7
Meancorpuscular 2732 3032 3033 2932 5

hemoglobin(pg/cell)
Meancorpuscular 7993 8196 8297 8199 5,6,13,1

volume(xm 3)
Platelet(x10 9/L) 165415 174391 155409 146429 5,6,14,1

17
Meanplateletvolume 6.411.0 7.710.3 7.810.2 8.210.4 5

(mcm 3)
Redbloodcellcount 4.005.20 3.424.55 2.814.49 2.714.43 5,6,13,1

(x10 6/mm 3)
Redcelldistribution <14.5 12.514.1 13.413.6 12.715.3 5

width(percent)
Whitebloodcellcount 3.59.1 5.713.6 5.614.8 5.916.9 5,6,13,1

(x10 3/mm 3) 18
Neutrophils 1.44.6 3.610.1 3.812.3 3.913.1 5,14,16,1

(x10 3/mm 3)
Lymphocytes 0.74.6 1.13.6 0.93.9 1.03.6 5,14,16,1

(x10 3/mm 3)
Monocytes 0.10.7 0.11.1 0.11.1 0.11.4 5,14,18

(x10 3/mm 3)
Eosinophils 00.6 00.6 00.6 00.6 14,18

(x10 3/mm 3)
Basophils(x10 3/mm 3) 00.2 00.1 00.1 00.1 14,18
Transferrin(mg/dL) 200400 254344 220441 288530 4,5
Transferrin,saturation 2246 Notreported 1044 537 3

withoutiron(percent)

Transferrin,saturation 2246 Notreported 1892 998 3
withiron(percent)
Coagulation
Antithrombin,functional 70130 89114 78126 82116 17,19,20

(percent)
Ddimer(mcg/mL) 0.220.74 0.050.95 0.321.29 0.131.7 17,2024
FactorV(percent) 50150 7595 7296 6088 25
FactorVII(percent) 50150 100146 95153 149211 17
FactorVIII(percent) 50150 90210 97312 143353 17,25
FactorIX(percent) 50150 103172 154217 164235 17
FactorXI(percent) 50150 80127 82144 65123 17
FactorXII(percent) 50150 78124 90151 129194 17
Fibrinogen(mg/dL) 211496 244510 291538 301696 5,17,20,

23,24,87
Homocysteine(mmol/L) 4.410.8 3.3411 2.026.9 3.221.4 6,9,101
International 0.91.04 0.861.08 0.831.02 0.801.09 19,24

NormalizedRatio
Partialthromboplastin 26.339.4 23.038.9 22.938.1 22.635.0 5,17,19,

time,activated(sec)
Plasminogenactivator 17.3+/5.7 17.7+/1.9 Notreported 66.4+/4.9 87

inhibitor1(PAI1)
antigen(pg/mL)
Plasminogenactivator 9.3+/1.9 9.0+/0.8 Notreported 31.4+/3.0 87

inhibitor1(PAI1)
activity(arbitraryunits)
Prothrombintime(sec) 12.715.4 9.713.5 9.513.4 9.612.9 5,17,24
ProteinC,functional 70130 78121 83133 67135 19,25,26

(percent)
ProteinS,total 70140 39105 27101 33101 17,25,26

(percent)
ProteinS,free(percent) 70140 34133 19113 2065 25,26
ProteinS,functional 65140 5795 4268 1642 25

activity(percent)
Tissueplasminogen 1.613 1.86.0 2.366.6 3.349.20 17,19,87

activator(ng/mL)
Tissueplasminogen 443 1633 3655 6792 17

activatorinhibitor1
(ng/mL)
vonWillebrandmeasurements
vonWillebrandfactor 75125 62318 90247 84422 20,27,28

antigen(percent)
ADAMTS13,von 40170 40160 22135 38105 20,28

Willebrandcleaving
protease
Bloodchemicalconstituents
Alaninetransaminase 741 330 233 225 4,5,8,29

(units/L)
Albumin(g/dL) 4.15.3 3.15.1 2.64.5 2.34.2 2932
Alkalinephosphatase 3396 1788 25126 38229 4,5,8,29

(units/L)
Alpha1antitrypsin 100200 225323 273391 327487 5

(mg/dL)
Alphafetoprotein Approximately Approximately 95

(ng/mL) 130400 130590
Ammonia(microM) 31+/3.2 27.3+/1.6 94
Amylase(units/L) 2096 2483 1673 1581 4,5,33,3
Aniongap(mmol/L) 716 1317 1216 1216 5
Aspartatetransaminase 1238 323 333 432 4,5,8,29

(units/L)
Bicarbonate(mmol/L) 2230 2024 2024 2024 5
Bilirubin,total(mg/dL) 0.31.3 0.10.4 0.10.8 0.11.1 4,29
Bilirubin,unconjugated 0.20.9 0.10.5 0.10.4 0.10.5 5,29

(mg/dL)
Bilirubin,conjugated 0.10.4 00.1 00.1 00.1 29

(mg/dL)
Bileacids(mmol/L) 0.34.8 04.9 09.1 011.3 29,35
CA125antigen 7.227.0 2/2268 1225.1 16.843.8 88,89,90

(units/mL)
Calcium,ionized 4.55.3 4.55.1 4.45.0 4.45.3 5,31,36,

(mg/dL)
Calcium,total(mg/dL) 8.710.2 8.810.6 8.29.0 8.29.7 4,5,30,3

3638
Ceruloplasmin(mg/dL) 2563 3049 4053 4378 5,39
Chloride(mEq/L) 102109 101105 97109 97109 4,5,40
Creatinine(mg/dL) 0.50.9 0.40.7 0.40.8 0.40.9 4,5,46
Gammaglutamyl 958 223 422 326 4,5,8,29

transpeptidase(units/L)
Lactatedehydrogenase 115221 78433 80447 82524 4,5,32,8

(units/L)
Lipase(units/L) 343 2176 26100 41112 33
Magnesium(mg/dL) 1.52.3 1.62.2 1.52.2 1.12.2 4,5,303

36,38
Osmolality(mOsm/kg 275295 275280 276289 278280 38,41

H20)
Phosphate(mg/dL) 2.54.3 3.14.6 2.54.6 2.84.6 4,5,30,3

42
Potassium(mEq/L) 3.55.0 3.65.0 3.35.0 3.35.1 4,5,15,3
32,38,40
Prealbumin(mg/dL) 1734 1527 2027 1423 5
Protein,total(g/dL) 6.78.6 6.27.6 5.76.9 5.66.7 5,31,32
Sodium(mEq/L) 136146 133148 129148 130148 4,5,15,3

32,38,41
Ureanitrogen(mg/dL) 720 712 313 311 4,5,40
Uricacid(mg/dL) 2.55.6 2.04.2 2.44.9 3.16.3 4,5,41
Metabolicandendocrinetests
Aldosterone(ng/dL) 29 6104 9104 15101 43,44,45
Angiotensinconverting 967 138 136 139 39,46

enzyme(units/L)
Alphafetoprotein 08.5 Notreported 50425 50590 84,86

(ng/mL)
Cortisol(mcg/dL) 025 719 1042 1250 5,45
HemoglobinA 1C 46 46 46 47 36,47,48
(percent)
Parathyroidhormone 851 1015 1825 926 30

(pg/mL)
Parathyroidhormone <1.3 0.70.9 1.82.2 2.52.8 30

relatedprotein(pmol/L)
Renin,plasmaactivity 0.39.0 Notreported 7.554.0 5.958.8 40,44

(ng/mL/hour)
Thyroidstimulating 0.344.25 0.603.40 0.373.60 0.384.04 4,5,49

hormone(milliint.
units/mL)
[AmericanThyroid 0.12.5 0.23.0 0.33.0 85

Association
recommendation]**
Thyroxinebinding 1.33.0 1.83.2 2.84.0 2.64.2 5

globulin(mg/dL)
Thyroxine,free(ng/dL) 0.81.7 0.81.2 0.61.0 0.50.8 5,49
Thyroxine,total 5.411.7 6.510.1 7.510.3 6.39.7 5,32

(mcg/dL)
Triiodothyronine,free 2.44.2 4.14.4 4.04.2 Notreported 49

(pg/mL)
Triiodothyronine,total 77135 97149 117169 123162 5

(ng/dL)
Vitaminsandminerals
Copper(mcg/dL) 70140 112199 165221 130240 50,51,5
Selenium(mcg/L) 63160 116146 75145 71133 5,50
VitaminA(retinol) 20100 3247 3544 2942 5

(mcg/dL)
VitaminB12(pg/mL) 279966 118438 130656 99526 6,10
VitaminC(ascorbicacid) 0.41.0 Notreported Notreported 0.91.3 52
(mg/dL)
VitaminD,1,25 2545 2065 72160 60119 30,36
dihydroxy(pg/mL)
VitaminD,24,25 0.55.0 1.21.8 1.11.5 0.70.9 53

dihydroxy(ng/mL)
VitaminD,25hydroxy 1480 1827 1022 1018 30,53

(ng/mL)
VitaminE(tocopherol) 518 713 1016 1323 5

(mcg/mL)
Zinc(mcg/dL) 75120 5788 5180 5077 5,13,50
Autoimmuneandinflammatorymediators
C3complement(mg/dL) 83177 6298 73103 77111 5
C4complement(mg/dL) 1647 1836 1834 2232 5
Creactiveprotein 0.23.0 Notreported 0.420.3 0.48.1 54

(mg/L)
Erythrocyte 020 457 747 1370 55

sedimentationrate
(mm/hour)
ImmunoglobulinA 70350 95243 99237 112250 5

(mg/dL)
ImmunoglobulinG 7001700 9811267 8131131 678990 5

(mg/dL)
ImmunoglobulinM 50300 78232 74218 85269 5

(mg/dL)
Sexhormones
Dehydroepiandrosterone 1.36.8 2.016.5 0.97.8 0.86.5 56

sulfate(mmol/L)
Estradiol(pg/mL) <20443 , 1882497 12787192 61373460 56,57
Progesterone(ng/mL) <120 848 99342 56,57
Prolactin(ng/mL) 020 36213 110330 137372 30,47,57
Sexhormonebinding 18114 39131 214717 216724 56,59

globulin(nmol/L)
Testosterone(ng/dL) 686 25.7211.4 34.3242.9 62.9308.6 56
17 0.610.6 , 5.228.5 5.228.5 15.584 56

hydroxyprogesterone
(nmol/L)
Lipids
Cholesterol,total <200 141210 176299 219349 5,6062

(mg/dL)
Highdensity 4060 4078 5287 4887 5,6063

lipoproteincholesterol
(mg/dL)
Lowdensitylipoprotein <100 60153 77184 101224 5,6063

cholesterol(mg/dL)
Verylowdensity 640 1018 1323 2136 62

lipoproteincholesterol
(mg/dL)
Triglycerides(mg/dL) <150 40159 75382 131453 4,5,606
ApolipoproteinAI 119240 111150 142253 145262 4,47,61

(mg/dL)
ApolipoproteinB 52163 5881 66188 85238 4,47,61

(mg/dL)
Cardiacfunction
Cardiacoutput(L/min) 4.86.8 5.69.7 5.59.9 4.88.7 64,65,66

68
Cardiacindex 2.64.2 3.24.6 3.14.7 2.54.4 65,68

(L/min/m 2)
Strokevolume(mL) 7990 77.5107.6 70.3107.6 5499 65,68,69
Strokeindex(mL/m 2) 4662 3962 3042 65
Systemicvascular 7001600 7471485 6921201 10341201 65,67,70

resistance(dyns/cm 5)
Echocardiography
Intraventricularseptal 0.70.9 0.630.83 0.650.85 0.660.9 68,69,70

dimension(cm) 92
Posteriorventricular 0.750.9 0.560.8 0.590.9 0.590.9 68,69,70

walldimension(cm) 92
Leftventricularmass 116143 108167 115150 128162 68,70,91

(g)
Leftventricularmass 4078 5379 5882 6088 68,70,91

index
E/Aratio 1.41.75 1.6 1.4 1.3 68,70
Leftventriculardiastolic 4.34.8 4.34.6 4.44.9 5.1 69,70

diameter(cm)
Leftventricularsystolic 2.83.1 2.82.9 2.83.4 2.83.3 69,70

diameter(cm)
Leftvent,fractional 3536 3537 3.5 3536 69,70

shortening(percent)
Leftventejection 6073 6175 6163 6073 69,70

fraction(percent)
Cardiacfunction(bloodtests)
Atrialnatriureticpeptide Notreported Notreported 28.170.1 Notreported 73

(pg/mL)
Btypenatriuretic <167(ageand 18.4 13.529.5 15.546 71,72,73

peptide(pg/mL) genderspecific)
Creatinekinase 39238 2783 2575 13101 5,74

(units/L)
CreatinekinaseMB <6 1.82.4 74

(units/L)
Nterminalprobrain 50+/26 60+/45 60+/40 43+/34 96
natriureticpeptide
(pg/mL)
TroponinI(ng/mL) 00.08 Notreported Notreported 00.064 75,76

(intrapartum)
Bloodgas
pH 7.387.42 7.367.52 7.407.52 7.417.53 31,77

(arterial) (venous) (venous) (venous)
7.397.45
(arterial)
PO 2 (mmHg) 90100 93100 9098 92107 77,78
PCO 2 (mmHg) 3842 Notreported Notreported 2533 77
Bicarbonate(HCO 3 ) 2226 Notreported Notreported 1622 77

(mEq/L)
Renalfunctiontests
Effectiverenalplasma 492696 , 696985 6121170 595945 79,80

flow(mL/min)
Glomerularfiltration 106132 131166 135170 117182 79,80,81

rate(GFR)(mL/min)
Filtrationfraction 16.924.7 14.721.6 14.321.9 17.125.1 79,80,81

(percent)
Osmolarity,urine 500800 326975 2781066 2381034 82

(mOsm/kg)
24halbuminexcretion <30 515 418 322 82,83

(mg/24hours)
24hcalciumexcretion <7.5 1.65.2 0.36.9 0.84.2 15

(mmol/24hours)
24hcreatinine 91130 69140 55136 50166 15,80

clearance(mL/min)
24hcreatinine 8.814 10.611.6 10.311.5 10.211.4 82

excretion(mmol/24
hours)
24hpotassium 25100 1733 1038 1135 15

excretion(mmol/24
hours)
24hproteinexcretion <150 19141 47186 46185 83

(mg/24hours)
24hsodiumexcretion 100260 53215 34213 37149 15,41

(mmol/24hours)
*Unlessotherwisespecified,allnormalreferencevaluesarefromtheseventeentheditionof
Harrison'sPrinciplesofInternalMedicine [84] .
Rangeincludesreferenceswithandwithoutironsupplementation.
Normalreferencerangeisspecificrangeforfemales.
ReferencevaluesarefromCernecaetal:Coagulationandfibrinolysischangesinnormalpregnancy
increasedlevelsofprocoagulantsandreducedlevelsofinhibitorsduringpregnancyinducea
[19]
hypercoagulablestate,combinedwithareactivefibrinolysis [19] .
ReferencesvaluesarefromCernecaetalandChoietal:Tissueplasminogenactivatorlevelschange
withplasmafibrinogenconcentrationsduringpregnancy [17,19] .
ReferencevaluesarefromMannucietal:Changesinhealthanddiseaseofthemetalloproteasethat
cleavesvonWillebrandfactor [28] .
ReferencevaluesarefromBacqYetal:Liverfunctiontestsinnormalpregnancy:aprospective
studyof102pregnantwomenand102matchedcontrols [29] .
ReferencevaluesarefromthefifteentheditionofHarrison'sPrinciplesofInternalMedicine [85] .
**TheAmericanThyroidAssociationrecommendstheseTSHrangesifindividuallaboratoriesdonot
determinetheirowntrimesterspecificreferenceranges.
Rangeisforpremenopausalfemalesandvariesbymenstrualcyclephase.
ReferencevaluesarefromLeiserowitzGSetal:CreatinekinaseanditsMBisoenzymeinthethird
trimesterandtheperipartumperiod [74] .
ReferencevaluesarefromDunlopW:Serialchangesinrenalhaemodynamicsduringnormal
humanpregnancy [79] .
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inMalaywomen.JMaternFetalMed8:95,1999[PMID:10338062].
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Copyright2010TheMcGrawHillCompanies,Inc.
Coagulationcascadeoverview
Thisschematicshowsarevisedversionofthecoagulationcascade
thatemphasizestheimportanceofpathwaysforhemostasisinvivo.
TissuefactorexposedatawoundinteractswithfactorVIIaand
initiatesclottingbytwopathways:(1)activatonoffactorXtoXa(ie,
theextrinsictenasecomplex)and(2)conversionoffactorIXtoIXa,
whichactivatesfactorXtoXa(ie,theintrinsictenasecomplex).
Pathways1and2areequallyimportant.
Inathirdpathway(3),thrombinalsoactivatesfactorXItoXIa,which
canleadtofurthergenerationoffactorIXathisisrequiredduring
severehemostaticchallenges.
CoagulationfactorsareshownasRomannumerals.Onlytheactivated
forms(withthesuffix"a")areshowninthisdiagramforsimplicity.
ThrombinisalsoknownasfactorIIa.
Componentsoftheplasmafibrinolyticsystem
Molecular
Activity
weight(d)
Plasminogen 88,000(singlechain) Proenzymeformoffibrinolyticenzyme
Plasmin 88,000(twochain) Activefibrinolyticenzyme
TPA 70,000(one/two Enzymepresentintissuesthatcovertsplasminogen

chain) toplasmin
UPA 54,000(twochain) Plasminogenactivator(differentfromtPA)
2PI 70,000(singlechain) Specificfastactinginhibitorinplasma
PAI1 40,000(singlechain) FastactinginhibitoroftPA(andUPA)secretedby

endothelialcells)
d:DaltonsTPA:tissueplasminogenactivatorUPA:urokinaselikeplasminogenactivator2PI:
alpha2plasmininhibitorPAI1:plasminogenactivatorinhibitor1.
Regulationoffibrinolysisbyplasminogenactivator
inhibitor1(PAI1),2antiplasmin,andthrombin
activatablefibrinolysisinhibitor(TAFI)
PAI1inhibitsplasminformationbyinhibitingtissuetypeplasminogen
activator(tPA).2antiplasmininhibitstheactivityofplasmin,thereby
inhibitingfibrinolysis.TAFIcirculatesinplasmaasazymogen.Itis
activatedbythrombinwhenthrombinisboundonendothelial
thrombomodulin,andthereforerepresentsalinkbetweenbloodcoagulation
andfibrinolysis.Duringfibrinolysis,plasmincleavesintactfibrinatlysine
residues,initiallyyieldinglarge,insolublefibrinfragmentswithlysine
residuesattheircarboxyltermini.PlasminogenbindsavidlytoCterminal
lysineresidueswithinthepartiallydegradedfibrinclotandassumesa
conformationthatissusceptibletoactivationbytPA,therebypromoting
plasminformation,continuedfibrinolysis("rapidlysisbyplasmin"),and
generationofsmaller,solublefibrinfragmentsthataredispersedbyflowing
blood.ActivatedTAFI(TAFI a )isacarboxypeptidasethatremoveslysine
residuesfromthecarboxy(C)terminiofpartiallydegradedfibrinfragments.
ByremovingCterminallysineresiduesfromlargefibrinfragmentsinthe
partiallydegradedclot,TAFIinhibitsrecruitmentofplasminogentotheclot,
therebyslowingfibrinolysis("slowlysisbyplasmin").
DiagramsuppliedbyWilliamPFay,MD.
Disclosures
Disclosures:KennethABauer,MDConsultant/AdvisoryBoards:JanssenPharmaceuticals
[Anticoagulation(Rivaroxaban)]DaiichiSankyo[Anticoagulation(Edoxaban)]Portola
Pharmaceuticals[Anticoagulationreversal,anticoagulation(Andexanet,betrixaban)]Instrumentation
Laboratory[Coagulationinstruments/reagents(ACLTOPinstrumentsandreagents)].CharlesJ
Lockwood,MD,MHCMConsultant/AdvisoryBoards:Celula[Aneuploidyscreening(Prenataland
cancerDNAscreeningtestsindevelopment)].KristenEckler,MD,FACOGNothingtodisclose.
JenniferSTirnauer,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,these
areaddressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsfor
referencestobeprovidedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofall
authorsandmustconformtoUpToDatestandardsofevidence.
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Author SectionEditor DeputyEditors

Nonpregnant First Second Third

Erythropoietin 427 1225 867 14222 13

Ferritin (ng/mL) 10150 6130 2230 0116 18

Folate,redbloodcell 150450 137589 94828 109663 6,9,10

Folate,serum(ng/mL) 5.418.0 2.615.0 0.824.0 1.420.7 1,6,913

Haptoglobin(mg/mL) 25250 130+/43 115+/50 135+/65 93

Hemoglobin (g/dL) 1215.8 11.613.9 9.714.8 9.515.0 2,3,6,7,

Hematocrit (percent) 35.444.4 31.041.0 30.039.0 28.040.0 1,2,5,6,

Iron,totalbinding 251406 278403 Notreported 359609 7

Iron,serum (mcg/dL) 41141 72143 44178 30193 2,7

Meancorpuscular 2732 3032 3033 2932 5

Meancorpuscular 7993 8196 8297 8199 5,6,13,1

Platelet(x10 9/L) 165415 174391 155409 146429 5,6,14,1

Meanplateletvolume 6.411.0 7.710.3 7.810.2 8.210.4 5

Redbloodcellcount 4.005.20 3.424.55 2.814.49 2.714.43 5,6,13,1

Redcelldistribution <14.5 12.514.1 13.413.6 12.715.3 5

Whitebloodcellcount 3.59.1 5.713.6 5.614.8 5.916.9 5,6,13,1

Neutrophils 1.44.6 3.610.1 3.812.3 3.913.1 5,14,16,1

Lymphocytes 0.74.6 1.13.6 0.93.9 1.03.6 5,14,16,1

Monocytes 0.10.7 0.11.1 0.11.1 0.11.4 5,14,18

Eosinophils 00.6 00.6 00.6 00.6 14,18

Basophils(x10 3/mm 3) 00.2 00.1 00.1 00.1 14,18

Transferrin(mg/dL) 200400 254344 220441 288530 4,5

Transferrin,saturation 2246 Notreported 1044 537 3

Antithrombin,functional 70130 89114 78126 82116 17,19,20

Ddimer(mcg/mL) 0.220.74 0.050.95 0.321.29 0.131.7 17,2024

FactorV(percent) 50150 7595 7296 6088 25

FactorVII(percent) 50150 100146 95153 149211 17

FactorVIII(percent) 50150 90210 97312 143353 17,25

FactorIX(percent) 50150 103172 154217 164235 17

FactorXI(percent) 50150 80127 82144 65123 17

FactorXII(percent) 50150 78124 90151 129194 17

Fibrinogen(mg/dL) 211496 244510 291538 301696 5,17,20,

Homocysteine(mmol/L) 4.410.8 3.3411 2.026.9 3.221.4 6,9,101

International 0.91.04 0.861.08 0.831.02 0.801.09 19,24

Partialthromboplastin 26.339.4 23.038.9 22.938.1 22.635.0 5,17,19,

Plasminogenactivator 17.3+/5.7 17.7+/1.9 Notreported 66.4+/4.9 87

Plasminogenactivator 9.3+/1.9 9.0+/0.8 Notreported 31.4+/3.0 87

Prothrombintime(sec) 12.715.4 9.713.5 9.513.4 9.612.9 5,17,24

ProteinC,functional 70130 78121 83133 67135 19,25,26

ProteinS,total 70140 39105 27101 33101 17,25,26

ProteinS,free(percent) 70140 34133 19113 2065 25,26

ProteinS,functional 65140 5795 4268 1642 25

Tissueplasminogen 1.613 1.86.0 2.366.6 3.349.20 17,19,87

Tissueplasminogen 443 1633 3655 6792 17

vonWillebrandfactor 75125 62318 90247 84422 20,27,28

ADAMTS13,von 40170 40160 22135 38105 20,28

Alaninetransaminase 741 330 233 225 4,5,8,29

Albumin(g/dL) 4.15.3 3.15.1 2.64.5 2.34.2 2932

Alkalinephosphatase 3396 1788 25126 38229 4,5,8,29

Alpha1antitrypsin 100200 225323 273391 327487 5

Alphafetoprotein Approximately Approximately 95

Ammonia(microM) 31+/3.2 27.3+/1.6 94

Amylase(units/L) 2096 2483 1673 1581 4,5,33,3

Aniongap(mmol/L) 716 1317 1216 1216 5

Aspartatetransaminase 1238 323 333 432 4,5,8,29

Bicarbonate(mmol/L) 2230 2024 2024 2024 5

Bilirubin,total(mg/dL) 0.31.3 0.10.4 0.10.8 0.11.1 4,29

Bilirubin,unconjugated 0.20.9 0.10.5 0.10.4 0.10.5 5,29

Bilirubin,conjugated 0.10.4 00.1 00.1 00.1 29

Bileacids(mmol/L) 0.34.8 04.9 09.1 011.3 29,35

CA125antigen 7.227.0 2/2268 1225.1 16.843.8 88,89,90