Patient posture for blood collection by venipuncture: recall for standardization after 28 years

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Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Original

article

Patient

posture

for

blood

collection

by

venipuncture:

recall

for

standardization

after

28

years

Gabriel

Lima-Oliveira

∗

,

Gian

Cesare

Guidi,

Gian

Luca

Salvagno,

Elisa

Danese,

Martina

Montagnana,

Giuseppe

Lippi

UniversityofVerona,Verona,Italy

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t

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Articlehistory:

Received29October2016 Accepted23January2017 Availableonline22February2017

Keywords:

Pre-analyticalvariability Posture

Plasmavolumechange Hematology

Completebloodcellcount

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b

s

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Background:Althoughdataabouttheeffectofpostureonroutinehematologicaltestingwere published28yearsago,thispre-analyticalissuehasnotbeenstandardizedsofar.Thisstudy wasplannedtoevaluatewhetherpostural changesinfluencetheresultsofhematology testing.

Methods:Acompletebloodcountwasperformedin19healthyvolunteersafter25mininthe supineposition,20mininasittingpositionand20minstationarystandinginanupright position.

Results:Thechangefromsupinetosittingpositioncausedclinicallysignificantincreases inthehemoglobin,hematocritandredblood cellcount.Furthermore,thechangefrom supinetostandingcausedclinicallysignificantincreasesinthehemoglobin,hematocrit, redbloodcell,leukocyte,neutrophil,lymphocyte,basophilandplateletcounts,andmean plateletvolume,andthatfromsittingtostandingcausedclinicallysignificantincreasesin hemoglobin,hematocrit,andredbloodcell,leukocyte,neutrophilandlymphocytecounts.

Conclusion: Theresultsofthisinvestigationprovidefurthersupporttothenotionthateffort should bemade toachieve widespreadstandardization inthe practiceof phlebotomy, includingpatientposture.

©2017Associac¸ ˜aoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.Published byElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

The complete blood count (CBC) is one of the tests most frequentlyrequestedinthe clinicalpractice,becauseitisa

∗ _{Correspondingauthorat:SectionofClinicalBiochemistry,DepartmentofNeurosciences,BiomedicineandMovementSciences,}

Univer-sityofVerona,Verona,Italy.

E-mailaddress:dr.g.lima.oliveira@gmail.com(G.Lima-Oliveira).

multi-taskinganalysisthatprovidesvaluableinformationon abroadrangeofclinicalconditions(i.e.,anemia,hemostasis, inflammation,malignancies).1_{ThesamplesforCBCarehence}

routinelyrequestedinvirtuallyallhealthcareenvironments, includingemergencydepartments,andclinicalandsurgical

http://dx.doi.org/10.1016/j.bjhh.2017.01.004

1516-8484/©2017Associac¸ ˜aoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

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revbrashematolhemoter.2017;39(2):127–132

wards.2_{Moreover,bothhematocritandhemoglobinareuseful}

forscreeningblooddonors.

In general, drawing of ethylenediaminetetraacetic acid (EDTA)-anticoagulatedspecimensbyvenipuncture(i.e.,those usedforCBCtesting)canbeperformedwithpatientsin dif-ferentposturesincludinglyinginbed,afterwalkingthrough ambulatoryservicesandsittingjustbeforethetest(i.e.,less than3min) orsitting foralong time(i.e.,afterperforming intravenousinfusiontherapyindaycarefacilities).

TheClinicalandLaboratoryStandardsInstitute(CLSI) H03-A6 document, renamed the GP 41-A6 standard, currently recommendsthatbloodspecimensshouldbecollectedwith the patient comfortably seated in an appropriate chair or lyingdown,butdoesnotprovidespecificationsaboutsupine orstanding positionsandtime ofpermanenceinacertain position.3 _{Since the posture may influence the}

concentra-tionofseveralblood constituentsduetodecreased plasma volumeoccurringonchangingfrom lyingtostanding,4 _itis

conventionallyassumedthatremainingsupineforalongtime maybeassociatedwithconsistenthemodilution.Ontheother hand,thestandingposturemaybeacauseofblood concen-trationduetotheeffectofgravitationalforceandhydrostatic pressure, which cause ultrafiltration of plasma and small moleculesintheinterstitialspace.5

Itisacommonexperiencethatcliniciansnotonlycomplain aboutunexpectedvariationsinhemoglobinlevels,especially whentheseapproximatethetransfusionthreshold,6_butalso

frequentlyappraisevirtuallyunexplainablechangesin addi-tionalparametersoftheCBC,suchasplateletsortheleukocyte countanddifferential.Itisnowclearlyacknowledgedthatthe vastmajorityoflaboratoryerrorsoccurinthepre-analytical phaseand are primarilyattributabletoalackof standard-izedprotocolsduringvenousbloodsampling.7,8_{Theinfluence}

ofpostureontheCBCwasinvestigatednearly30yearsago byLeppanenandGrasbeck,9_{whomanuallymeasuredwhite}

blood cell (WBC) differential counts in 22 healthy women after2hfasting.9 _{Theseauthors recommendedthatvenous}

bloodsamplingshouldbestandardizedtoareferenceposition, eithersitting or supine.However,this experimentaldesign –entailing2hoffasting10_{andmanualanalysis}11_–isbarely

reproducibleaccordingtothecurrentpracticeandtechnology. Therefore,thisstudywasplannedtoevaluatewhether postu-ralchangesinfluencetheresultsoftheCBC,withspecialfocus onplatelets,leukocytecountanddifferential.

Methods

Thestudypopulationconsistedof19healthysubjects(mean age44±11years;sevenmaleand12female)recruitedfrom thelaboratorystaffoftheUniversityHospitalofVerona(Italy). Venousbloodwascollectedafterovernightfasting(12h)bythe standardtechniqueandwithoutvenous stasis.12,13 _Inbrief,

three5.9mgofK2EDTAbloodtubes(Venosafe,TerumoEurope

N.V.,Leuven,Belgium)werecollectedfromeachvolunteeron thesameday. Thefirsttube wasdrawnafter25mininthe supineposition,thesecondafter20mininthesittingposition andthelastafter20mininthestandingposition.Blood col-lectionswereseriallyperformedintheorderlistedabove,and theintervalswereonlythosespentineachposture.TheCBC

wasperformedwiththeAdvia2120hematologicalanalyzer (Siemens Healthcare Diagnostics, Deerfield, IL). The delta plasmavolumechange(PVC)wascalculatedwiththe ref-erenceformulaofDillandCostillasfollows:PV(%)=100× ((Hemoglobinpre/Hemoglobinpost)×(100−Hematocritpost)/

(100−Hematocritpre)−1), using hematocrit values as

per-centages and hemoglobin values in g/dL.14 _{Results are}

expressed as medians and interquartile range (IQR). The significance of differences was evaluated with Wilcoxon’s signedranktest,usingAnalyse-it(Analyse-itSoftwareLtd., Leeds, UK). The percentage variation calculated from the different postural positions was also compared with the desirablequalityspecificationsforbiasderivedfrom biologi-calvariations15_{asprovidedbyRicosetal.Briefly,thisisbest}

achieved for measurands under strict homeostatic control in order topreserve their concentrations inthe body fluid ofinterest,but it canalsobeappliedtoother measurands thatareinasteadystateinbiologicalfluids.Inthiscase,it is expectedthat the ‘noise’produced bythe measurement procedure willnotsignificantlyalterthesignalprovidedby theconcentrationofthemeasurand.16_{Eachpatientprovided}

writtenconsentbeforebeingenrolledinthestudy,whichwas performedinaccordwiththeethicalstandardsestablished bytheinstitutioninwhichtheexperimentswereperformed andtheHelsinkiDeclarationof1975.

Results

TheresultsofthisstudyareshowninTable1andFigure1. According tothe formulaofDill andCostill,thePVC was −3.4%fromsupinetositting,−14.1%fromsupineto stand-ingand−9.3%fromsittingtostanding.Statisticallysignificant variationsfromsupinetosittingwerefoundfortheredblood cell(RBC),WBC,neutrophil,lymphocyte,eosinophil,basophil andplateletcounts,hemoglobinandhematocrit.Whenthese variations were compared to the quality specifications for bias derived from biological variations, meaningful differ-enceswereonlyobservedfortheRBCcount,hemoglobinand hematocrit.Statisticallysignificantvariationsfromsupineto standingwererecordedfortheRBC,WBC,neutrophil, lympho-cyte, eosinophil, basophil, andplatelet counts,hemoglobin andhematocritandmeancorpuscularvolume(MPV).When thesevariationswerecomparedagainstthequality specifica-tions,meaningfuldifferenceswerefoundfortheRBCcount, hemoglobin, hematocrit,andWBC,neutrophil, lymphocyte, basophil,andplateletcountsandMPV.Furthermore, statisti-cally significantvariationsfromsittingtostandingposition were observed forthe RBC count, hemoglobin, hematocrit, WBC,neutrophil,lymphocyte,basophil, andplateletcounts andMPV.Whenthesevariationswerecomparedtothequality specifications,meaningfulbiaswasfoundfortheRBC,WBC, neutrophilandlymphocytecounts,hemoglobinand hemat-ocrit.

Discussion

Theresultsofthisinvestigationconfirmthatthepatient pos-ture hasanimpact onthetestresultsofanumberofCBC parameters.Thiswasevidentforboththeplateletcountand

rev bras hema tol hemoter. 2 0 1 7; 3 9(2) :127–132

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bias Value p-Value vs.supine Bias(%) vs.supine Value p-Value vs.supine Bias(%)vs. supine p-Value vs.sitting Bias(%)vs. sitting PVC(%variation) – – −3.4(−1.5to−4.3) <0.001 – −14.1(−9.1to−15.7) <0.001 −9.3(−11.1to−6.6) <0.001 – RBCcount(×1012_{/L) ±1.7% 4.7(4.4–5.2) 4.8(4.5–5.3) <0.001 2.2(1.8–2.8) 5.0(4.7–5.4) <0.001 6.8(5.1–9.0) <0.001 4.9(2.8–5.9)} Hemoglobin(g/L) ±1.8% 131(127–145) 134(129–150) <0.001 2.3(1.9–2.9) 141(134–154) <0.001 7.1(5.3–8.9) <0.001 4.8(3.9–6.0) Hematocrit(%) ±1.7% 0.41(0.40–0.44) 0.42(0.41–0.44) 0.009 1.7(1.3–2.5) 0.44(0.43–0.47) <0.001 6.9(5.0–8.9) <0.001 5.3(3.3–6.3) MCV(fL) ±1.3% 89(87–92) 90(87–92) 0.057 – 90(87–92) 0.420 – 0.670 – MCH(pg) ±1.3% 29.2(27.7–30.0) 29.5(28.0–30.3) 0.145 – 29.2(28.1–30.2) 0.147 – 0.170 – RDW(%) ±1.7% 13.4(12.9–13.9) 13.4(12.9–13.8) 0.424 – 13.4(12.9–14.1) 0.176 – 0.178 – WBCcount(×109_{/L) ±6.0% 5.4(4.6–6.7) 5.7(4.9–6.1) <0.001 5.1(3.2–8.1) 6.2(5.3–6.7) <0.001 17.1(14.2–24.2) <0.001 15.6(8.2–18.8)} Neutrophils(×109_{/L) ±9.2% 3.2(2.4–3.5) 3.3(2.5–3.7) <0.001 4.3(2.9–8.0) 3.7(3.0–4.1) <0.001 15.2(12.6–25.9) <0.001 12.3(7.7–16.8)} Lymphocytes(×109_{/L) ±9.2% 1.7(1.2–2.0) 1.8(1.2–2.1) <0.001 6.9(4.5–7.8) 1.9(1.5–2.5) <0.001 23.4(14.1–34.9) <0.001 17.9(9.3–23.9)} Monocytes(×109_{/L) ±13.2% 0.28(0.23–0.32) 0.28(0.22–0.32) 0.325 – 0.28(0.24–0.32) 0.117 – 0.054 –} Eosinophils(×109_{/L) ±19.8% 0.07(0.06–0.11) 0.08(0.06–0.13) 0.008 10.0(0.0–17.1) 0.09(0.06–0.13) 0.009 13.3(0.0–34.3) 0.284 –} Basophils(×109_{/L) ±15.4% 0.02(0.01–0.03) 0.02(0.02–0.03) 0.008 0.0(0.0–50.0) 0.03(0.02–0.04) <0.001 50.0(12.5–66.7) 0.012 0.0(0.0–50.0)} LUC(×109_{/L) Not} available 0.13(0.12–0.14) 0.13(0.10–0.14) 0.145 – 0.13(0.11–0.16) 0.259 – 0.054 – Platelets(×109_{/L) ±5.9% 194(181–233) 200(190–243) <0.001 4.1(2.1–6.3) 210(198–248) <0.001 10.9(4.6–14.8) 0.002 4.7(0.0–8.8)} MPV(fL) ±2.3% 8.9(8.5–9.3) 8.9(8.3–9.3) 0.122 – 8.8(8.1–9.1) 0.018 −2.3(−4.5to−0.5) 0.041 −1.3(−3.3to0.5)

Resultsareexpressedasmediansandinterquartilerange,significantdifferencesareinbold.

PVC:plasmavolumechange;WBC:whitebloodcell;LUC:largeandunstainedcells;RBC:redbloodcell;MCV:meancorpuscularvolume;MCH:meancorpuscularhemoglobin;RDW:redbloodcell

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revbrashematolhemoter.2017;39(2):127–132 8.0% 20.0% 15.0% 10.0% 5.0% 0.0% –5.0% –10.0% –15.0% 30.0% 25.0% 20.0% 15.0% 10.0% 5.0% –10.0% 0.0% –5.0% –15.0% 25.0% 20.0% 15.0% 10.0% 5.0% 0.0% –15.0% –5.0% –10.0% –20.0% –25.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% –1.0% –2.0% –3.0% 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% –1.0% –2.0% –3.0% 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% –1.0% –2.0% –3.0% 20.0% 12.0% 3.0% 2.0% 1.0% 0.0% –1.0% –2.0% –3.0% 10.0% 8.0% 6.0% 4.0% 2.0% 0.0% –2.0% –4.0% –6.0% –8.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% –10.0% –20.0% 15.0% 10.0% 5.0% 0.0% –5.0% –10.0%

Baseline Sitting Baseline

vs. Supine Sitting vs. Supine Standing vs. Supine Standing vs. Supine Baseline Sitting vs. Supine Standing vs. Supine RBC Hb Ht WBC Platelets Neutrophils Lymphocytes Eosinophils Basophiles MPV DSI– DSI– DSI– DSI– DSI– DSI– DSI– DSI– DSI+ DSI+ DSI+ DSI– DSI– DSI+ DSI+ DSI+ DSI+ DSI+ DSI+ DSI+ Standing vs. Sitting Baseline Sitting vs. Supine Standing vs. Supine Standing vs. Sitting Baseline Sitting vs. Supine Standing vs. Supine Standing vs. Sitting Baseline Sitting vs. Supine Standing vs. Supine Standing vs. Sitting Baseline Sitting vs. Supine Standing vs. Supine Standing vs. Sitting Standing vs. Sitting Baseline Sitting vs. Supine Standing vs. Supine Standing vs. Sitting Baseline Sitting vs. Supine Standing vs. Supine Standing vs. Sitting Baseline Standing vs. Supine Standing vs. Sitting

Figure1–Interferogramsrelatedtopatientpostureduringbloodcollectionbyvenipuncture.Patientposture(x-axis)is plottedagainstbiasvalues(y-axis).Solidline–bias.Dashedlines–acceptablecriteriabasedondesirablespecificationfor imprecision(DSI)derivedfrombiologicvariation.

MPVthat were significantlybiasedwhen patients changed positionfromstandingtothesupineposition(Table1).MPV is an important parameter in the differential diagnosis of patientswiththrombocytopenia,17 _{andforrisk assessment}

ofcardiovasculardisorders.18_{Aclinicallysignificantbiaswas}

alsoobservedforleukocytes.Interestingly,increasesinthe WBC,neutrophil, lymphocyte,andbasophilcountswereon average2-to5-foldlargerthanexpectedaccordingtothe cal-culatedPVC(Table1).Thisevidencesuggeststhatanactive releaseofleukocytesmayoccurfromdynamicreservoirs,such asthespleen,whenthepatientchangesfromthesupine posi-tiontostanding.19

TheCBChas asubstantial diagnostic valueinthe daily clinicalpractice.Whencarefullyinterpretedaccordingtothe clinical history of signs and symptoms, this analysis pro-videsusefulinformationinthediagnosisandmanagementof patientswithanumberofhematologicaldisorders.TheCBC isalsohelpfulforlongitudinalmonitoringofRBCs,platelets andleukocytesinresponsetodrugand/orsurgicaltreatment. However,aftertheintroductionofautomatedbloodcount ana-lyzers, a complete panel of blood cell indices can now be generatedwith amuchhigher degree ofanalytical quality andaccuracy,20_{andthusmucheffortisrequiredto}

standard-izeextra-analyticalissues(i.e.,patientpostureduringblood collectionbyvenipuncture).21–23

The influence of patient posture on blood components hasbeeninvestigatedpreviouslywithspecialfocusonlarger moleculessuch asalbumin, serum enzymes,bilirubin and lipoproteins.4,6,24–28 _{Mayer et al. first studiedthe influence}

ofpostureon hematocritand demonstrated that achange ofposition fromrecumbenttositting wassufficientto sig-nificantlyincreasethehematocrit,withstandingproducing anevengreaterincrease.24_{Mawetal.alsoinvestigatedthe}

underlyingmechanisms of this modification by measuring body fluid rearrangement during postural variations, and concludedthatintravascularfluidlossduringstandingwas mainlyduetofiltrationofplasmaintotheinterstitium.29_More

recently,Inagakietal.demonstratedthattheredistributionof waterbetweenthe intra-and extra-vascularspaces follow-ingposturalchangesduringhemodialysiswasanimportant sourceofchangesinblood components,thusunderpinning theimportanceofposturaleffectsforevaluatingblood param-etersduringhemodialysis.30

Thefindings ofthis study have somepotentially useful clinicalimplications.First,theevidencethatseveral param-etersoftheCBCaresignificantlyaffectedbydifferentpostural positionsraisesthecrucialissuethatpatientpostureshould beaccuratelystandardizedduringblooddrawing,especially whendefiningreferencerangesformanylaboratorytestsand assessing longitudinalvariations of the same subject over time.Asecondimportantaspectisthatphysiciansshouldnot discountthefactthatvirtuallyinexplicablevariationsofRBC, plateletsandleukocytesmaybecausedbythecollectionof venousbloodindifferentposturesratherthanbydisease(e.g., acutebleeding,plateletconsumptionasinthecaseof dissem-inatedintravascularcoagulation),oranalyticalerrors.Thisis particularlycrucialforparameterssuchastheWBCand lym-phocytecounts,whichincreasedbyapproximately20%from supinetostandingposition(Table1andFigure1).Finally,we alsoraisetheissuethatguidelinesforvenipuncturesuchas

thoseoftheCLSI3_{shouldincludeaclearindicationthat}

stan-dardizingpatientpostureisnecessarytoproducesoliddata andenablereliablecomparisonsovertime.

Conclusions

Inconclusion,theresultsofthisinvestigationprovidefurther supporttothenotionthateffortshouldbemadetoachieve awidespreadstandardizationofthepracticeofphlebotomy. Clearindicationsshouldbegiventhatpatientpostureduring venousbloodsamplingmustbestandardizedtoareference position,eithersittingorsupine.Irrespectiveofthechosen criterion,arecommendationshouldbegiventhataminimum period (i.e., 15 or 20min) ofresting in the reference posi-tion should beobservedbefore collectingvenousblood for CBC.

Authorship

GLO, GLS, GCG and GL conceivedand designed the study, analyzed the data, performed the statistical analysis and draftedthemanuscript;EDandMMreviewedtheliterature, acquired data, interpretedthe resultsand criticallyrevised themanuscript.Alltheauthorsreadandapprovedthefinal versionofthemanuscript.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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