Documento

Especificaciones de la caUdad analiticaen laboratorios c1inicoscon distintos niveles de recursosSociedad Espanola de Bioqulmica C1fnica y PUlologfa MolecularCamite de Garantra de 1:1 Calidad y Acredilaci6n de Laboratorios 'Comisi6n de Calidact Analltica

DOClllllcnto V. Fase 3. Versi6n I

QUfMICA CLINICA 2000: 19 (3) 219-236

Preparado por C. Ric6s. Y. Alvarez. F. Cava. J. V. Garda-Lario. A. Hernandez. C. V. Jimenez. J. Minchinela.C. Perich. M. Sim6n

fndicc

oObjcli\'o delli.homlorioJ ApliclIciones cspccffic:ls2 Aplic:l(;ioncs generales3 OblCllci6n de los indiC,HJorcs de 1,[ calid,HJ analfliclI4 Umilcs dcriv<ldos de III \'ariaci6n biol6gic:l5 Discusi6n6 Conclusioncs7 Bibliogmfia81\11<.",'(0:.

oOBJETIVO DEL LABORATORIO

Ellabor.uorio dinico debe m.cgur..r que I.. inform<lci6n produ­cida MllisfilCC las nt."'ec!'oidadc:. de los solieit:mles. MIS usuariosdin::ctm. los medicos. E~. por talllo. Illuy import:lIlIe idemificarla aplicadon que elmcdico dara a los dalOs :malfticos y que ell,lbor,lIorio colabore en hI imerprel;lci6n del informe. comoulla pUrle esenci,,1 del proceso de la decisi6n dfnica.

I APLICACIONF..5 ESPECiFiCAS

En principio. ~i sc pudier:1 determinar de form:l objeliva cU:IIe~ d ni\'c! de ealidad requerido para l'ada ~ituacion clinicaconcrCla, cI laboralorio deberia basal' sus cMrale~ia~de aCIU:J­ci6n en alcanzar la~ el>pecificacione~adecuada' para cadacaM). Sin embargo. esta pmibilidad no es looa"fa rc:llisla en la'Icllmlid:ld. salvo p:lr.l dClenninadas prucbas aplicada':1 proto­colo~ c1fnicos c1aram('llI(' definidos en all1bito~ muy hX.":lliza­do... (por ejemplo. helllo~lobin:lAle en p;lcient('l> di:lbCticos)(I). Para qu(' esta opcion pueda lIe\'arse a 1:1 pr.lcliea, cs neee­sarin desarrollar mClodos de Irabajo que objelil'en los requeri­lllienlllS el{nicos y asesoren las decisiones subsectlentes p;lr"delerlllinar cl gr;ldo de fi,lbilidad arl;lliliCii <.:"1';11. de informal'sobre eI verdadero e~lado de .,alm! del p,lCiellte (2.3). E...la cs.

'(",""1"......"'" d.... c..,,,,,t: ~u. ,\1,,1>:1. V. Ah=~. I'. c~,"- \1 Conb.J.V. G~",i~.l-""", A. Hcndndr/.• C VJun" I. J. ~nnm' ....1a, J \1 )l.a\""",C. J'<"r><h. I' Rallo(,., (1'r<".,d<"nl"l. C R A. Sala•. ,\1 S",,,,"

pues, una opcion de futuro quc no puede apliearse looavfa enla pnictica asislcndal :IClual.

2 APLICACIONES GENERALES

Elllcrminos generales, las razones de lo.s c1inicos para solicitarpruebas de laboralorio son cuatro:

I. Crib'ldu. que es la idenlificacion de un gnlpo de paciellle~

con riesgo de est:lr afectados pol' una delerminada palOlogfa,con n::Spt.'CIO:1 la pobl:lci6n £eneraL

2. Idelllifieaci6n del caso individual. que cs la disc-rimina­ei6n dd eSlado de salud de un paciente indi\'iduul. en principio:Isimomatico. EI tennino coloquial ..chequeo» es mas conoci­do en nuestro mcdio pur" designar e.S1e conccplo

3. Diagnostico. que es la idclllificaci6n de la P.110logia con­cn::I:1 que afecla al pacieme indh'idual.

4. Monilorizal'i6n, <Iue es el se~uimiento de 1;1 e\'oluci6n ddIM:icnle individual.

Ell los Ires primeros casos, d laboralorio debe priorizar MI

alencion en la capacidad dc oblener cI verdadcro n::sulwdo de I..lIlagnillid biol6gica a dClerminar. Aunque las posibles causas deerror no solo rcsiden crt la rase analftica. eSle es cI proceso mejorconlrol:ldo hoy dia en ellaboflltorio dfnleo y es cI objelO de c.stedocumento. EI componente de error analftico que se debe mante­ocr :ICOIado cs d error ...i~lem.ilieo. En cI cuarto l'U.-.o, d labor,lto­rio debe ser capaz de mantener idcnlico~ n::~ultadol>en unali~i~

n::pctidos de la mil>llta m:l£nilud y. pol' t:mIO. cI componente decrmt a minimi7.ar cs d ermt alcalorio (impn.'Ci..i6n analfliea).

Hay que Icner en cuema. ~in embargo. que lo~ compon('nte..del error analflico no aCluan de fonna complcl:llncntc indepcn­diem(', AsL en el diagnoslim y cribado una cxcc... ivu impn.'Ci·.. ion pllede provocar la idenlific:lei6n err6ne:l de un nUlIlero im­IXlr1;mle de l~asos individuales. En cl M'guimiento de paci(,llle~

en el tiel11po, cuartdo se dcben comp:lrar los re ... ultados obleni­dos con respeclo a "'lImes discriminanles, e.s muy illlportanlccorllrolar y minimizar cl cOmlXlnenle de erTOI" ... i...lel1lalil~O.

Por clio. es inlen::sanle delerminar l'on daridad y, a ser IXll>i­ble, con nilcrios biologicos 1>:lr:I <Iue l>U aplic:lCi6n en dink'a seae1k;l/, los Ifmit('s de acepwbilidad p:1r,l I~ errorc~ l>il>tem:'itico yak<llOrio. M'p;lf:ldarnellie. p;lra disponer dc al:lrma,) n::'olvcr~1Il> e<lU...:b en d rnOIllCnlO dCllCado. En cuamo al error 100aL quee.. cl que afccl:1 a la, lIluc...lr:I' de paciClll(,'" (una dt.'lemlinaci6nliniea, dondc c., impo...iblc de.loCOmponer cI error analftico en l>U~

dOll integfllnle... princip;lle...), tambicn el> 1ll..'C<:,ario e...lablccer ,u,lflllilel> de :Iccpl:lbilidad P:1r.1 poder minimil:lr didlO error.

Quimic;rClinic;r 199x: 19(3) 119

3 OBTENCION DE LOS INDICADORES DE LACAUDAD ANALiTICA

EI procedimicnto de control interno de la calidad analflicaproporciona la medida del error sistematico (difcrencia entre lamedia de n dClenninacioncs control y eI valor diana. expresa­da en porccntajc sabre cl valor diana) y del error aleatorio (co­cficicllie de variaci6n de /I observ:lciOllcs comrol). La partici­pllci6n en programas de ev:duaci6n extern:l de 1:1 calidad:lllaliticn (conlro1es no diarios analizados una 501:1 vcz) facilil<lla mcdida del error IOllll (difcrcncia entre un rcsultado controly cl valor diana. exprcsada en porcenlajc rcspccto al valor dia­na). En eSlc caso. se pueden promcdiar datos procedcmcs deperiodos de tiempo largos. POT cjcmplo un ano. lcnicndo 1:1precauci6n de considerar s6lo cI valor absoluto de las diferen­cias obtcnidas (de 10 contrario sc subestimaria. debido al efec­to compcnsador de posibles signos opuestos).

Como diana. se debe tomar cl valor oblenido por labora~

torios que utilizan el propio mctodo. ya que en nuestro me­dio no se dispone de valores aponados por Inctodos de re­ferencia.

4 LiMITES DERIVADOS DE LA VARIACIONBIOLOGICA

Los datos derivados de la vanaci6n bio16gica han sido amplia­mente aceptados para definir Iimites de tolerancia para impre­cision. error sistematico y error total de las determinacionesanaliticas. COilove et al (4) propugnaron <Jue si se mantiene laimprecision por debajo de la mitad dc la variac ion biol6gicaintr:tindividu.d. cI posible error aportado par la mcdici6n anali~

tiea queda acotlldo al 10.8% sobre la variabilidad global de lamuestra. Gowans (5) demostro que si sc mantiene el error sis­tematico par debajo de la cuarta parte de la suma vectorial dela variaci6n biol6gica imra e inlerindividual. laboratorios queatiendan a una misma poblaci6n pueden eompartir los valoresde referencia poblacionales. qucdando solo fuera de Iimites su­perior e inferior. respectivamente. el 4% y el 1% de individuossanos. En ambos casos. cl riesgo de incumplimiento de la afir­m3ci6n mencionad3 es inferior al 0.05.

Existe la posibilidad de tr:tbajar II otros niveles de riesgo. enfuncion de las dificuhades tcenieas y econ6micas de cada la­baratorio individual.Se han descrito tres niveles de prestaci6n analitica (6):

I. Minima:Imprecision (eVa) < 0.75 CVto;Error sistematico (ES.) < 0.375 (CVbi

2 + CV",2 )Jr.!Error total (ETa) < k·0.75 CVh• + 0.375 (CVhi

2 + CVbj; 2 )112

2. Deseable:Imprecisi6n (CVa ) < 0.5 CVIH

Error sistematico (ES.) < 0.25 (CV,/ + CV",2 )InError total (ETa) < k·O.5 CVbi + 0.25 (CVbo

2 + CV",2 )In

3.6ptimo:Imprecision (CV.) < 0.25 CV",Error sistematico (£Sa) < 0.125 (CVto;2 + CV",2 )In

Error 100al (ETa) < k·0.25 CVhi + 0.125 (CVbt2 + CVh/ )Jr.!

Siendo:- Cv, = eoeficientc de vllrillci6n analftieo- ES, = error sistematico analitico- 1:.7.. = error total ;1ll3Hlico- k = 1.65 (n<D.05). 0 bien k = 2.33 (n<O.OI)

220 Qufmica Clinica 2000: 19 (3)

- CVto; = Variacion biol6gica imraindividual. expresada enporcentaje respeclo al valor medio (sujetos sanos)

- CV'" = Variacion biol6gica interindividual. expresada enporcentaje rcspeclO al valor medio (sujetos sanos)

5 DISCUSION

Incrementllr la pcrmisividad pilra error totul al riesgo de 0.01implica una cierta incoherencitl con respccto a las estr<ltegiasde acotaci6n de sus eomponentes. pueslo que la mayorfa de lasreglas de control interno publicadas estan calculadas con unriesgo de 0.05. Aun asi. puede ser practico utilizar la opci6n0.01 como primera medida. que obligue a tomar acciones co­m.--CIOras inmcdiatas. Dc hecho. el Comitc ya rccomend6 cstoslfmites al explicar eSlralegias para eonseguir transferibilidadentre laboratorios (7). Ahom bien. en cuanto el procedimientoanalitico alcanza c6modamente este limite. debcrfa tratar demantencrsc de11lro de los mtirgenes delimitados par el ricsgode 0.05.

Las espedficaciones deseables scran el objctivo final paratodos las magnitudes biol6gicas. pero algunas veees son di­ficiles de alcanzar. El Comite sugiere que para magnitudesbioqufmieas detcrminadas por espectromctria con CV", < 6%Y para magniludes medidas por inmunoanalisis con CVb •

< 8%. se podrian ulilizar especifieaciones mfnimas. Propo.nelllos cSla frontera porque hemos constalado (progmlllas deevaluacion externa comereiales) que existen en el mercadomelodos analftieos de cada uno de estos tipos con impre­cisi6n inlcrlaboralOrios inferior a 3 y 4%. respectivamemc.indicando que los laboratorios quc los emplcan pueden al­eanzar la precisi6n deseable para realizar un correclO segui­miemo de los pacientes.

Cuando no se alcaneen las especificacioncs deseablt::s. es re­comendable observar la preslaci6n de los laboralorios del en­tomo. para ver si sc trata de una situaci6n aislada (instrumenta­ci6n amieuada. formaci6n deficitaria. etc.) o. par el conlrario.es genemlizada (metodo poco satisfactorio para la aplicaci6nclfnica de los datos dellaboratorio).

En los Anexos I y II se indican las especificaciones desea­bles y minimas (respectivameme) para imprecisi6n. error siste­matico y error total (a los dos niveles de riesgo rnencionadospreviamente) para 252 constituyellles determinados en diver­50S sistemas biol6gicos. ordenados alfabeticameme. Las tablasde valorcs se han elaborado a partir de un:l base de datos querecoge 191 artfculos can datos de \'ariaci6n biol6gica intra einlerindi\'idual. eSludiados en profundidad para eliminar losartfculos con escasa fiabilidad (8).

Pard constituyentes con \'ariacion biol6gica aha. los labo­ratorios que utilicen procedimientos analfticos precisos ycxactos podran alcanzar las especificaciones de prcstacion6ptima. En este caso. dcbcd.n utilizar reglas de control inter­no en coneordancia con sus objetivos molS CSlrictos. 10 eualles pcrmitir5 espaeiar la frecuencia de observaciones controly. en eonseeueneia. redueira sus costes directos. Algunosejemplos de especificaciones 6plima.~ se mucSlran en el Ane­xo III.

En cl Anexo IV sc prcscntan las rcfercncias bibliograficasutilizadas para obtener las cspecificacioncs de cada magnitudbiol6gica incluida en la base de dalos. En eI Anexo V se pre­scnta la relaci6n complela de los anfculos utilizados para cla­bordr dicha base de datos.

6 CONCLUSIONES

EI Comite de Gardmla de la Calidad y Acrcditacion de Labora-

torios recomienda que todos laboratorios alcancen con un gra­do de conllanza del 95% («0.05) la preslaci6n analftica dese­able. en cuanto sea posible. Sin embargo para aquellos laOOra­tori os que no puedan lIegar a este nivel de inmediato. sediscuten aqui los pros y coniras de las restantes alternativas.

7 BIBLIOGRAFiA

I. Lytten Larsen M. F,....ser CG, Hylton Petersen P. A comparison ofanalytical goals for Haemoglobin A Ie assays <kori"l'd using diffc .....mslrategics. Ann Clin Biochcm 1991 :28:272·8.

2. Thue G. Sanberg S. Fugcl1i I', Clinical a"e'SlIlelll of hemoglobin va­lues by general practieioner, relatcd to analytical and biological va·rhlliun. A sludy based on case hislorie,. Scan J Clin Lab Invest1991 :51 :453-9.

3. Sandberg S. Thuc G. Quality specifications derived fmm objectiveanalyses based Upoll medical needs. En: Stralegies to sct global qua­lity spccificatiolls in laboratory medicine. Scan J Clin Lab Ilivest1999.

4. Cotlo"e E. Harris EK. Williams Gz. Biol~ical and analytic compo­I1C'nts of variation in long-term swdles of serum consUlucnlS in normalsubjects. 3. Physiological and medical implications. Clin Chern1970:16:1028-32.

5. Gowans EMS. Hyhoft Ptttrsen P, Blaabjerg O. I-Iorder M. Anal)1icalgoal for the accept:lnL'f: or commoo refereoce inlervals for I:lbor:alorie:sthroughouIl!'eol!'raphical area. Scao J ClIO Lab In"est 1988:48:154·Il-l.

6. Fr..ser CG. I-Iyllofl Peten.en I', Libccr Jc. Rico,; C. Proposals for Sd­ting gcnerJlIy applicabk lIuality goals solely based on biology. AnnClin Biocheml997:34:8·12.

1. Suo:;ie<J:td Espanola dc Bioqu(mica C1inica y Patologi<l Molecular. Co­l11il~ dc Garamfa dc ]a CaliJ:ul y A<:reJil<lcion de L<lbonllOrios. Trans­fcribilidad de los result:ldos I'roducidos en el labor:uorio cHnio::o.Quint Clin 1996: 15:442·4/1997: 16:21l:'l.

II. Rio:;o,; C. Alva .....z v, Cava 1'. Garcia-Lario IV. Hernandez A. JimenezCV. MinchilleJa J. Perich C. Simon M. Currenl dambascs un biologi­0:;:11 "ariation: pillS. cons and progress. So::all J Clin L:tb In ....:st 1999:59: 491-500.

Com:spondeocia:Soe-icd3d Esp;IDoI;J. de Bi~uimica Clink;! f Patologia Moleo::ularComilc de Garantia de Cahtbd y Acredila600 de labor.llorioscI Padilla 32.1-325. desp. 6808025 Barcelona

QufmicaClinica2000: 19(3) 221

ANt:XO I. Especificaciones deseables para la impredsion. error sistematico)' error lotal

MAGNITUO BIOl6GICA Variacion BiolOgica Esp«iricaciones Oeseablesev. ev.. CV. (%) £5.(%) £T.(%) ET.(%)

P<O.05 P<O.OI

Sml·II·Dcsoxicortisol 21.3 31.5 10.7 9.5 27.1 34.3Sr111·17.Hidrox iprogcslcrona 19.6 52.4 9.8 14.0 30.2 36.8dUriA-hidroxi-3-mclOximandelalO (VMA) 22.2 47.0 11.1 13.0 31.3 38.9Snn-5' -Nucleotidasa 23.2 19.9 11.6 7.6 26.8 34.7dUri-5-Hidroxiindolacetalo.conccntmci6n 20.3 33.2 10.2 9.7 26.5 33ASnll-CXI-Antiqui miOiripsi na 13.5 IS.3 6.8 5.7 16.S 21..1Snn-a ,-Antitripsina 5.9 16.3 3.0 4.4 9.3 11.3Srm,(X,-Glicoproteina acida 11.3 24.9 5.7 6.8 16.2 20.0Srm-o:,-Globulina 11.4 22.6 5.7 6.3 15.7 19.6Uri-(Xl·Microglobulina concenlrtlci6n. primem micci6n 33.0 5S.0 16.5 16.7 43.9 55.1Pla-a~·Anliplasmina 6.2 ._- 3.1 --- --- ---Srm.(X~-Globulina 10.3 12.7 5.2 4.1 12.6 16.1Srm-(X~-Macroglobul ina 3.4 IS.7 1.7 4.8 7.6 8.7Uri-(XrMicroglobulina. flujo. primera micci6n 29.0 32.0 14.5 10.8 34.7 44.6Srm-(X·Amilasa 9.5 29.8 4.8 7.8 15.7 18.9Srm·(X·Amilasa pancreatica 11.7 29.9 5.9 8.0 17.7 21.7Uri-a-Amilasa. conttntraci6n. alc310ria 94.0 46.0 47.0 26.2 103.7 135.7Srm-a-Caroteno 35.8 ._. 17.9 --- --- _.-Pac·Adaramiento de creatininio 13.6 13.5 6.8 4.8 16.0 20.6Srm-Adenosina-desaminasa 11.7 25.5 5.9 7.0 16.7 20.6Pla·Adrenalina 48.3 -- 24.2 --- -- ---Pqs-Adrenalina 25.3 _.- 12.7 -- --- ._-Srm.Agua 3.1 0.1 1.6 0.8 3.3 4.4Srm·Alanina·aminopcplidasa 4.1 ._- 2.1 --- ..- ---Srm· Alanina·aminOl ransfcrasa 24.3 41.6 12.2 12.0 32.1 40.4Srlll-AlbUmina 3.1 4.2 1.6 1.3 3.9 4.9Uri-Albumina. conccllIrad6n. primera micci6n 36.0 55.0 18.0 16.4 46.1 58.4Srm-Aldosterona 29.4 40.1 14.7 12.4 36.7 46.7dUri·Aldoslerona. concentraci6n 32.6 39.0 16.3 12.7 39.6 50.7dUri·Amonio. flujo 24.7 27.3 1204 9.2 29.6 38.0San.AmplilUd de dislribuci6n eriuocitaria 3.5 5.7 1.8 1.7 4.6 5.7San.AmplilUd de distribuei6n plaquelar 2.8 ..- 104 --- --- ._.

Snn-Androslendiona 11.5 51.1 5.8 13.1 22.6 26.5Sml-Anlfgeno CA 125 13.6 46.5 6.8 12.1 23.3 28.0Sml·Anllgcno CA 15.3 5.7 42.9 2.9 10.8 15.5 17.5Srm-Anlfgeno CA 19.9 24.5 93.0 12.3 24.0 44.3 52.6Srm-Antfgeno CA 549 9.1 33.4 4.6 8.7 16.2 19.3Sml-Antfgeno carcinocmbrionario 9.3 55.6 4.7 14.1 21.8 24.9Srm·Anligeno es~cffico de la proslata 14_0 72.4 7.0 1804 30.0 34.75nn-AllIigeno Me 10.1 39.3 5.1 10.1 18.5 21.9Srm-AllIigeno poli~plidieo lisular (TPA) 28.7 4004 14..1 12A 36.1 ~5.8

Srm-Antfgeno polipcplidico tisularespecifioo (TPS) 36.1 108.0 18.1 28.5 58.3 70.5Snn·Antfgeno SCC 39.4 35.7 19.7 13.3 45.8 59.2Pla·AllIitrombina 111 5.2 15.3 2_6 4.0 8.3 10.15rm.Apolipoprotefna A I 6.5 1304 3.3 3.7 9.1 11.3Snn.Apolipoprolcfna B 6.9 22.8 3.5 6.0 11.6 14.0Srm-AscorbalO 25.8 22.9 12.9 8.6 29.9 38.7Srlll-Aspartalo-am i1101 ransferasa 11.9 17.9 6.0 SA 15.2 19.2Srm-(X-Tocoferol 13.8 13.3 6.9 4.8 16.2 20.9Snn-~~-Microglobulina 5.9 15.5 3.0 4.1 9.0 11.0San-Bas6filo. rcCUCnlO 28.0 54.8 14.0 1504 38.5 ~8.0

Snn-~-Carolcno 36.0 39.0 18.0 13.3 43.0 55_1Snn·fl-Criptoxam ina 36.7 _.- ISA --- -_. .~.

Snn-fl-Globulina 10.1 9.1 5.1 3.4 11.7 15.2Srm·Bilirrubina 25.6 30.5 12.8 10.0 31.1 39.8Snn-Bilirrubina c~lcrificada 36.8 43.2 1804 1~.2 44.5 57.1Srm-ClIkio 1.9 2.8 1.0 0.8 1..\ 3.1dUri-Cakio. conccnlraci6n 27.5 36.6 13.8 1104 34.1 43.5dUri-Calcio. llujo 26.2 27.0 13.1 9.4 31.0 39.9Srm-Caplaci6n de Triiodolironina 4.5 4.5 2.3 1.6 5.3 6.8

222 Quimica Clinica 2000: 19(3)

MAGNITUI> RIOLOGICA Variacion Biologica Especificaciones Deseablesev. e" .... ev. (%) £S. (lk) £T.(%) £T.(%)

P<O.05 P<O.OI

dUri-Calecolaminal> 24.0 32.0 12.0 10.0 29.8 38.0Pla-Cistcfna 5.9 12.3 3.0 H 8.3 10.3Srm-Cloruro 1.2 1.5 0.6 0.5 1.5 1.9Plu-Cobre 8.0 19,0 4.0 5.2 11.8 14.5Srm-Cobre 4.9 13.6 2.5 3.6 7.7 9.3Srrn-Coleslerol 6.0 15.2 3.0 4.1 9.0 11.1Sml-Coleslerol de BDL 7.1 19.7 3.6 5.2 11.1 13.5Snn-Colesterol de HDLI 5.5 27.2 2.8 6.9 11.5 13.3Srm-Colestcrol de HDL2 15.7 40.7 7.9 10.9 23.9 29.2Srm-Colesterol de HDL3 7.0 14.3 3.5 4.0 9.8 12.1Srm·Colesterol de LDL 8.3 25.7 4.2 6.8 13.6 16.4Snn-ColeSlcrol de LDL (melodo dil"eCIO) 6.5 ... 3.3 ... ._- -..Srm-Colestcrol de VLDL 27.6 ..- 13.8 --- --- ---Snn-Colineslerusa 7.0 10.4 3.5 3.1 8.9 11.3Srlll-Col inc Slcr:lsa, illnlunorrem;livll 6.4 ..- 3.2 --- ..- _..Srm·Coli nesterOlsOl,Olctividad 5.4 10.3 2.7 2.9 7.4 9.2Srm-Componcnle C3 del Complcmcnlo 5.2 15.6 2.6 4.1 8.4 10.2Srm-Cnmponcnte C4 del Complemenlo 8.9 33.4 4.5 8.6 16.0 19.0(San)Ers-Concemraci6n corpuscular media de hcmoglobina LJ 2.8 0.9 0.8 2.2 2.8Snn·Conisol 20.9 45.6 10.5 12.5 29.8 36_9Srm·Crclllina-cina~ 22.8 40.0 11.4 11.5 30.3 38.1Snn-Crealina-cinasa 2. % 6.9 42.8 3.5 10.8 16.5 18.9Sml-Crealiml·cinul>a 2, aClividad 19.7 24.3 9.9 7.8 24.1 30.8Snll·Crcatina-cinasa 2. masa 18.4 61.2 9.2 16.0 31.2 37,4Srm·Creatininio 4.3 12.9 2.2 3.4 6.9 8.4dUri-Crealininio conccntraci6n 24.0 24.5 12.0 8.6 28.4 36.5dUri·CrcOllininio flujo 11.0 23.0 5.5 6.4 15,4 19.2dUri-DesoxipiridinolinalCrcalininio 14.7 15.1 7.4 5.3 17.4 22.4(SOln)Gas Di6xido de carbono 4.8 5.3 2.4 1.8 5.7 7.4Pla·Dipeplidil-pcptidasa IV 8.2 l·okS 4.1 4.2 10.9 13.7Pla-Elaslasa 13.6 16,4 6.8 5.3 16.5 21.San-Eosin6filos. recuento 21.0 76.4 10.5 19.8 37.1 44.3San-Eritrocitos. l\.'CuenlO 3.2 6.1 1.6 LJ 4.4 5.5Snn-Eslradiol 22.6 24.4 11.3 8.3 27.0 34.6Uri-Eslro1diol 30,4 --- 15.2 --- --- ---Srlll-E~lradio[ no unido 01 proteirw 22.8 ..- 11.4 ..- _.. _..Uri-Estradiol no Imido <I prolcfna 38.6 ..- 19.3 ..- _.. _..Srm-FOlclores reumaloideos 8.5 24.5 4.3 6.5 13.5 16,4Pla-FOlclor V de la coagulaci6n 3.• --- 1.8 --- --- ---PI,i-FaClor VII de In coagulaci6n 6.8 19.4 3.4 5.1 10,7 13.1Pla-Fa":lor VIII de la coagulaci6n 4.8 19.1 2.4 4.9 8.9 10.5Pia-Factor Von \Villcbr.tnd 0.001 18.3 0.0005 7.1 7.1 7.1Pia·FacIoI' X de la coagulaci6n 5.9 --- 3.0 --- --- ---Srm-Ferritina 14.9 13.5 7.5 5.0 17,3 22,4Snn-Fcrroxidasa (Ccrulopla:.minll) 5.7 11.1 2.9 3.1 7.8 9.8Pla-Fibrinogeno 10.7 15,8 5.4 4.8 13.6 17.2Srm-Folitropina 10.1 32.0 5.1 8.4 16.7 20.2Srm-FosfOllasa l'Icida 8.9 8.0 4.5 3.0 10,3 13.4Snn-Fosfalasa lkida prosl:hica. llclividad 33.8 --- 16.9 --- --- ---Srm-Fosfalasa fil-ida. 100nralo-resistelllC 10.8 13.3 5.4 4.3 13.2 16.9Srm-Fusfalasa "kalina 6.4 24.8 3.2 6.4 1l.7 13.9Snn-Fosfalasa alcalina. isocnzima 6sca 6.6 35.6 3.3 9.1 14.5 16.7Smi-Fosfatasa alcalina. isoen7.ima plllceniaria 19.1 --- 9.6 --- --- ---Sml-Fohfato 8.5 9.4 '.3 3.2 10.1 13.1dUri-Fosfato. concenlraci6n 26A 26.5 13.2 9.' 31.1 40.1dUri-Fosfalo. nujo 18.0 22.6 9.0 7.2 22.1 28.2Srm-Fosfolipido 6.5 11.1 3.3 3.2 8.6 10.8Snn-Fructosamina 3.4 5.9 1.J 1.J 4.5 5.7Srm-y·Globulina 14.6 12.3 7.3 4.8 16.8 21.8S1'111-y-G Iulami II rallsfcrasa 13.8 41.0 6.9 10.8 22.2 26.9

Quinlka Clinica 2000: 19 (3) 223

MAGNITUD BIOLOGICA Variacion 8iologica Especificaciones DesC:lblcsCVbl CVb~ CV. (%) ES. (%) ETa(%) ETa(%)

P<O.05 P<O.Ol

Srlll-G Iicoal btl m] na 5.2 10.3 2.6 2.9 7.2 8.9San-GIicohemoglobi na 5.6 --- 2.8 --- --- ---Srm-Globulina cnlazante de hormon<ls (SHBG) 12.1 42.7 6.1 ILl 21.1 25.2Srm-Globlilina enlazante dc liroxina (TBG) 6.0 6.0 3.0 2.1 7.1 9.1Srm-Globlilina 5.5 12.9 2.8 35 8.0 9.9Srlll-Glucosa 4.9 7.7 2.5 2.3 6.3 8.0(San)Ers-Glucosu-6-fosfato- I-deshidrogenasa 32.8 31.8 16,4 11.4 385 49.6S<ln-Gllitali6n-pcroxidasa 7.2 21.7 3.6 5.7 11.7 14.1Srlll- Haploglobi na 20,4 36.4 10.2 lOA 27.3 34.2San-HcmalocrilO 2.8 6A 1.4 1.7 4.1 5.0San-Hcmoglobina 2.8 6.6 1.4 1.8 4.1 5.1(San)Ers-Hellloglobina corpuscular media 1.6 5.2 0.8 1.4 2.7 3.2Snn-Hidroxiblltirato deshidrogenasa 8.8 --- 4.4 --- --- ---

dUri-Hidroxiprolinaiminulo 36.1 38.8 18.1 13.2 43.0 55.3Srlll-Hicrro (II + [II) 26,5 23.2 13.3 8.8 30.7 39.7Pla-Hotllocislelna 7.7 29.9 3.9 7.7 14.1 16.7Srm-Inmunoglobulina A 5.0 36.8 2.5 9.3 13.4 15.1Srm-Inlllunoglobulin<l G 4.5 16.5 2.3 4.3 8.0 9.5Srlll-Inlllulloglobulina M 5.9 47.3 3.0 11.9 16.1'1 18.8Srlll-Inmunoglubulinas cadcna K 4.8 15.3 2.4 4.0 8.0 9.6Snn-Inmunugloblilinas caden<l A 4.8 18.0 2.4 4.7 8.6 10.2Srm-Inslilina 21.1 58.3 10.6 15.5 32.9 40.1(San)Lks Ion POI<lsio 13.6 13.4 6.8 4.8 16.0 20.6Srm-Ion POlasio 4.8 5.6 2.4 1.8 5.8 7.4dUri-lon POlusio.conccntraci6n 27.1 23.2 13.6 8.9 31.3 40.5dUri-lon POlasio.lllljo 24.4 22,2 12.2 8.2 28.4 36.7(Sun)Ers-[on Sodio 1.8 12,4 0.9 3.1 4.6 5.2(San)Lks-lon Sodio 51.0 36.4 25.5 15.7 57.7 75.1Srm-Ion Sodio 0.7 1.0 0.4 0.3 0.9 1.1dUri-[on Sodio. wncentraci6n 24.0 26,8 12.0 9.0 28.8 37.0dUri-lon Sodio. lllljo 28.7 16,7 14.4 8.3 32.0 41.7Srm-Isocnzima I de Lact<lIO-deshidrogcllasa 6.3 10.2 3.2 3.0 8.2 10.3Srlll-Isocnzima 2 de Lactalo-dcshidrogen<ls:l 4.9 4.3 2.5 1.6 5.7 7.3Srlll-lsocnzinKt .1 dc Lactato-deshidrogcnasu 4.8 5.5 2.4 1.8 5.8 7.4Srrn-Isucnzima 4 de LactalO-deshidrogcnasa 9.4 9.0 4.7 3.3 11.0 14.2Srlll-Isocnzima 5 de Lactalo-dcshidrogenasa 12,4 13.4 6.2 4.6 14.8 19.0San-Lactato 27.2 16.7 13.6 8.0 30.4 39.7Srm-Llcluto-dcshidrogenasa 8.6 14.7 4.3 4.3 llA 14.3Pla-Lactofcrrina 11.8 23.7 5.9 6.6 16.4 20.4San-Lcucocitos. recucnlO 10.9 19.6 5.5 5.6 14.6 18.3Srm-Licopeno 43.1 --- 21.6 --- --- ---San-Linfocilos. n::cuenlo 10.4 27.8 5.2 7.4 16.0 19.5Srm-Lipasu 23.1 33.1 11.6 10.1 29.1 37.0Srm-Lipoproleina (a) 8.5 85.8 4.3 21.6 28.6 31.5Srm-Llileina 23.7 11.9Srm-Lulropina 14.5 27.8 7.3 7.8 19.8 24.7(San)Ers-Magncsio 5.6 1l.3 2.8 3.2 7.8 9.7(San)Lks Magnesio 18,3 16.4 9.2 6.1 21.2 27.5Srm-Magnesio 3.6 6.4 1.8 1.8 4.8 6.0dUri-Magnesio. concentraci6n 45.4 37.4 22.7 14.7 52.2 67.6dUri-Magncsio. tlujo 38,3 37.6 19.2 13,4 45.0 58.0Srm-Mioglobin,l 13.9 29.6 7.0 8.2 19.6 24.4San-MonocilOs. recucnlO 17.8 49.8 8.9 13.2 27.9 34.0Uri-N-Acel iI G IllCOS:tllli nidasa.concen Ir:lci6n 52.5 33.5 26.3 11.5 46.3 60.6Uri-N-Acetil Gilicosaminidasa.tlujo 42.4 18.2 21.2 11.5 46.5 60.9San-Nclllr61i1os. recuento 16.1 32.8 8.1 9.1 22.4 27,9dUri-Nitrogeno 13.9 24.2 7.0 7.0 18.4 23.2(San)Pqs-NoradrcnaIina 9.5 --- 4.8 --- --- ---Pln-Noradrenalina 19.5 --- 9.8 --- --- ---Srm-Osl11olalidad 1.3 1.2 0.7 0.4 1.5 2.0

224 QlIfmil:a Clinica 2000: 19 (3)

QU11l11C.l ClinlCI. _000. I) (.1J __5

MAGNITUD UIOLOGICA Variacillll Hioliigicli EspccilicllcioliCS DCSCllblcsCV,,; Cl'h~ C"o (%) ESa (%) ETa(%) ETa(%)

P<0.05 ['<0.01

Srm-Osteocalcina 6.3 23.1 3.2 6.0 11.2 13.3dUri-Oxalato. cOlh:entraci6n 44.0 18.0 22.0 11.9 48.2 63.1dUri-OxalalO. nlljo 42.5 19.9 21.3 11.7 46.8 61.2Srm-Peptidil dipeptidasa A (ECAj 12.5 27.7 6.3 7.6 17.9 22.2Snn-Pcptido C 9.3 13.3 4.7 4.1 11.7 14.9San-pH IH'I 3.5 2.0 1.8 1.0 3.9 5.1San-pH (lInid<ldcs de pH) 0.2 ... 0.1 ... ... ...Uri -Pirid inoli na/Creat inina. aJe.1toria 8.7 17.6 4.4 4.9 12.1 15.0San-Piruvato 15.2 13.0 7.6 5.0 17.5 22.7San-Plaquetas.rc(·uento 9.1 21.9 4.6 5.9 13.4 16.5San-Plaquetocrito 11.9 ... 6.0 ... ... ...PI a- PI asmi n6ge no 7.7 ... 3.9 ... . .. ...S1'111- Prelll bllm ina 10.9 19.1 5.5 5.5 I-U 18.2Snn-Prolaetilla 6.9 61.2 3.5 15.4 2 I. I 23.4Pla-Prolil EndorcPtid<lsa 16.8 13.9 8,4 5.5 19.3 25.0Srlll-Propeptido C-terminal procok'igeno tipo I 8.2 17.6 4.1 4.9 11.6 14,..1.Srm.Proreplido N-Icnninal procol:'igeno tipo [ 7.4 3.7Snn-Proteina 2.7 4.0 1,4 1.2 3,4 4,4Pla-Protcina C 5.8 55.2 2.9 13.9 18.7 20.6Srlll-Proteina C re'lCtiva 52.6 84,4 26.3 24.9 68.3 86.1Pla-Protcfna S 5.8 63,4 2.9 15.9 20.7 22.7Snn-Protcfna total glicad<l 0.9 11.6 0.5 2.9 3.7 4.0dUri-Protcina. concelltraci6n 39.6 17.8 19.8 10.9 43.5 57.0dUri-Protcfna. nlljo 35.5 23.7 17.8 10.7 40.0 52.0Pac-Reabsorci6n llIblilar de fosfato 2.7 3.3 1,4 l.l 3.3 4.2(S.m)Lks Receptor de interrcr6n 14.0 20.0 7.0 6.1 17.7 22.4San-Receptor LDL del RNAI11 21.5 13.6 10.8 6.4 24.1 31.4Srlll-Retinol 14.8 18.3 7.4 5.9 18.1 :23.1Pla-$elcnio 12.0 14.0 6.0 4.6 14.5 18.6$an-Sclcnio 12.0 12.0 6.0 4.2 14.1 18.2Snn-Sulfato de Deshidroepiandrosterona 3.4 30.0 1.7 7.5 10.4 11.5Srlll-Supcr6xido dismutasa 17.1 10.5 8.6 5.0 19.1 24.9(San)Ers-Surcr6x ido disllllltasa 12.3 4.9 6.2 3.3 13.5 17.6Uri-Telopeplido C-terminal eoliigeno lipo II crc;ninilla 35.1 17.6Snn-Telopcptido C-terminal procol.igeno tipo I 8.0 28.8 4.0 7.5 14.1 16.8Uri-Telopeptido N-terminal colagcno II ercatinina 23.1 11.6Slv-Testosterona 17.3 28.8 8.7 8,4 22.7 28.6Srl1\-Teslosterona 8.8 21.3 4.4 5.8 13.0 16.0Uri-Tcstosterona 25.0 .. 12.5 ... ... ...Srm-Tcstosteron" no unida a protcin" 9.3 ... 4.7 ... ... ...Uri-Tcstosteroll<l no lInida a proteina 51.7 ... 25.9 ... ... ...Pla-Ticmpo de protrombina 4.0 6.8 2.0 2.0 5.3 6.6Pia-Tielllpo dc trombopl<lstina parcial 2.7 8.6 1,4 2.J 4.5 5.4SI'm-Tiroglobul ina 13.0 25.0 6.5 7.0 17.8 22.2Srm-Tirotropina (TSH) 19.7 27.2 9.9 8.4 24.6 31.3Srm-Tiroxinn 6.0 12.1 3.0 3.4 8.3 10,..1.Snn-Tiroxina no lInid<l a protcfna 7.6 12.2 3.8 3.6 9.9 12.4Srm-Transfcrrina 3.0 4.3 1.5 1.3 3.8 4.8Srm-Transferrina dcficicntc en carbohidratos 7.1 38.7 3.6 9.8 15.7 18.1Srm-Triglicerido 20.9 37.2 10.5 10.7 27.9 35.0Srm-Triiodotironill<l 8.7 14.4 4,4 4.2 11.4 14.3Srm-Triiodotironina no lInida <I protcfn:l 7.9 ... 4.0 ... ... ...Srm-Urato 8.6 17.2 4.3 4.8 11.9 14.8dUri-Urato. concentracion 24.7 22.1 12.4 8.3 28.7 37.1dUri-Urato. lllljo 18.5 14.4 9.3 5.9 21. 1 27ASrm-Urca 12.3 18.3 6.2 5.5 15.7 19.8dUri-UrC'l. cuncell1raci6n 22.7 25.9 11.4 8.6 27.3 35.1dUri-Urea.llujo 17.4 25.4 8.7 7.7 22.1 28.0(SanjErs- Vollll11cn ('orpll~cll1ar mcdio 1.3 4.8 0.7 1.2 2.3 2.8(SanjPqs Volumcn plaqllctar Illcdio 4.3 8.1 2.2 2.3 5.8 7.3Srm-Zcax;\ntilw J.t] ... 17.4 ... ... ...Pia-Zinc 11.0 14.0 5.5 4.5 13.5 17.3Srm-Zinc 9.3 9A 4.7 3.3 11.0 1·.1,1, ,

"

ANEXQ II. Espccilicacioncs minimas para la impredsion. error sistematicu y errur total

!\'IAGNITUD BIQLOGICA Variadon Biol6gica I::spedlicaciones Minima.~

ev. ev", ev. (%) ES. (%) ET.(%) ET.(%)P<:0.05 P<O.OI

SmHll-Antitripsina 6.0 16.3 4.5 6.5 9.3 11.3Pla-a2-Anliplasmina 6.2 ... 4.7 ... ... ...Srm-a2-Macroglobulina 3.4 18.7 2.6 7.1 11.3 13.1Snn.Agua 3.1 0.1 2.3 1.2 5.0 6.6Srm-Alanina aminoPCPlidasa 4.1 ... 3.1 ... ... ...Srm-Albumina 3.2 4.2 2.4 2.0 5.9 7.6San-Amplilud de distribuci6n erilrocitaria 3.5 5.7 2.6 2.5 6.8 8.6San-Amplilud de distribuci6n plaquelar 2.8 ... 2.1 ... ... ...Srm-Amigeno CA 15.3 5.7 42.9 4.3 16.2 23.3 26.2Pla-Amitrombina 111 5.2 15.3 3.9 6.1 12.5 15.JSrm-ApoliJXlprotdna A I 6.5 13,4 4.9 5.6 13.6 16.9Snn-AIXJliIXJprolcfna B 6.9 22_8 5.2 8.9 17.5 21.0Snn'~rMicroglobulina 5.9 15.5 4.4 6.2 13.5 16.5Srm-Calcio 1.9 2.8 1.4 1.3 3.6 4.6Srm-Captaci6n de Triiodotironina 4.5 4.5 3.4 2.4 8.0 10.3Pla-Cisleina 5.9 12.3 4.4 5.1 12,4 15.4Snn-Cloruro 1.2 1.5 0.9 0.7 2.2 2.8Srm-Cobre 4.9 13.6 3.7 5.4 11.5 14.0Srm-Coleslerol de HDL 7.1 19.7 5.3 7.9 16.6 20.3Srm-Coleslcrol de HDLI 5.5 27.2 4.1 10,4 17.2 20.0Snn-Colcslerol de HDL3 7.0 14.3 5.3 6.0 14.6 18.2Srm-Colcstcrol de LDL (metodo directo) 6.5 ... 4.9 .•. ... ...Snn-Colineslcrasa 7.0 10,4 5.3 4.7 13,4 16.9Srm-Col incstemsa. inmunorrcacliva 6.4 ... 4.8 ... ... ...Srm-Colinestcr.lsa.ilcliyidild 5,4 10.3 •. 1 4.4 11.0 13.8Snn-Componcnlc C3 del Complclllcnio 5.2 15.6 3.9 6.2 12_6 15.3(San)Ers-Conccnlmci6n corpusculilr media de ht:moglobina 1.7 2.8 1.3 1.2 3.3 4.2Srm·Crcatina·cinasa 2 6.9 42.8 5.2 16.3 24.8 28.3Snn-Crcatininio 4.3 12.9 3.2 5.1 10,4 12.6(San)Gas-Di6xido dc carbona 4.8 5.3 3.6 2.7 8.6 Il.lSan-EritrociloS. rccucnto 3.2 6.1 2,4 2.6 6.5 8.2Pia-Factor V de la coagul:lci6n 3.6 ... 2.7 ... ... ...Pia-Factor VII de 101 coagulaci6n 6.8 19.4 5.1 7.7 16.1 19.6Pla-FaClor VllI dc I" congulaci6n 4.8 19.1 3.6 7.4 13.3 15.8Pla-Fnclor X de III coagulaci6n 5.9 ... 4.4 ... ... ...Pla·FaClor Von Willcbnmd 0.001 28.3 0.0 10.6 10.6 10.6Srm- Fcrrox idas'l (Ccru 10pl:lSI11 ina) 5.7 11.1 4.3 4.7 11.7 14.6Srm-Fosflltasu aleulina, isocnzinm 6sca 6.6 35.6 5.0 13,6 21.7 25.1Srm-FruclOSal1l ina 3.4 5.9 2.6 2.6 6.8 8.5Srm-GIiCOlllbul1l ina 5.2 10.3 3.9 4.3 10.8 13,4San-GIicohc moglobi na 5.6 ... 4.2 ... ... ...Srm-Globulina enlazalll~ de liroxina (TBG) 6.0 6.0 4.5 3.2 10.6 13.7Sml-Globulin:I.lolal 5.5 12.9 4.1 5.3 12.1 14.9Snn-GIUI:lti6n-pcroxidas:1 7.2 21.7 5,4 8.6 17.5 21.2San-Hematocrito 2.8 6.4 2.1 2.6 6.1 7.5San-Hemoglobina 2.8 6.6 2.1 2.7 6.2 7.6(San)Ers-Hcmoglobina corpuscular media 1.6 5.2 1.2 2.0 4.0 4.8Pla-Homocistcfna 7.7 29.9 5.8 11.6 21.1 25.0Snn.lnmunoglobulina A 5.0 36.8 3.8 13.9 20.1 22.7Snn-Inmunoglobulina G 4.5 16.5 3.4 6,4 12.0 14.3Srm-Inmunoglobulina M 5.9 47.3 4,4 17.9 25.2 28.2Srm-Inmunoglobulinas cadena" 4.8 15.3 3.6 6.0 12.0 14,4Sml·lnmunoglobulina.~ cadena). 4.8 18.0 3.6 7.0 12.9 15,4Sml~lon Potasio 4.8 5.6 3.6 2.8 8.7 11.2Son-Ion Sodio 0.7 1.0 0.5 0.5 U 1.7(San)ET!>-lon Sodio 1.8 12,4 1,4 4.7 6.9 7.8Snn-lsocnzima I de LaclalCHicshidrogenilsil 6.3 10.2 4.7 4.5 12.3 15.5Snn·lsocnzima 2 de Laclato-deshidrogcnasa 4.9 4.3 3.7 2,4 8.5 11.0Sml-lsoenzima 3 de Laclalo-deshidrogcnasa 4.8 5.5 3.6 2.7 8.7 ILlSnn-LiIXJproldna fa) 8.5 85.8 4.3 21.6 28.6 31.5

226 Quimica Clinica 2000: 190)

MAGNITUO BIOLOGICA Variacion Hiol6gica Espt-'Cilicaciones minimasev. ev.. CV. (%) £5. (%) ET.(%) ETa(%)

P<O.05 P<O.OI

(San)Ers-Magnesio 5.6 11.3 4.2 4.7 11.7 1-l-.5Srm-Magnesio 3.6 6.4 2_7 2.8 7.2 '.0Srm-Osmolalidad 1.3 1.2 1.0 0.7 2.3 2.9Srm-<hteoca1cina 6.3 23.1 4.7 '.0 16.8 20.0San-pH 3.5 2.0 2.6 1.5 5.8 7.6Pla.Plasmin6geno 7.7 5.8Sml-Prolaclina 6.' 61.2 5.2 23.1 31.6 r7-:).-

Sml-Propeplido N-terminal procolageno tipo I 7.4 5.6Srm-Proleina 2.7 4.0 2.0 1.8 5.2 6.5Pla·Proteina C 5.8 55.2 4.4 20.8 28.0 30.9Pla-Prolclna S 5.8 63.4 4.4 23.9 31.1 3-'.0Srm-Prolcfna lotal glicada 0.' 11.6 0.7 4.4 5.5 5.9Pac-Reubsorci6n tubular de fosfato 2.7 3.3 2.0 1.6 4.' 6.3Srm-SulfalO de Deshidroepiandrosleronu 3.4 30.0 2.6 11.3 15.5 17.3P1:I.Ticmpo de prolrombina 4.0 6.8 3.0 3.0 7.' •••Pla-Ticrnpo de lromboplaslina parcial 2.7 8.6 2.0 3.4 6.7 8.1

Srm-Tiroxina 6.0 12.1 4.5 5.1 12.5 15.5Srm-Tiroxinu no uniJa a protefna 7.6 12.2 5.7 5.4 14.8 18.7Srlll-Transfcrrina 3.0 4.3 2.3 2.0 5.7 7.2Snn·Tmnsfcrrina ddicicnte en cllrbohidrJIOS 7.1 38.7 5.3 14.8 23.5 27.2Srm-TriioJOlironina no unida a proteina 7.' 5.'(San)Ers-Volumen corpuscular medio 1.3 4.8 1.0 I.' 3.5 4_1

(San)P(IS Volumen plaquetar medio 4.3 8.1 3.2 3.4 8.8 11.0

Quirnio.:a Clfnica 2000: 19 (3) 227

ANEXO III. Especificaduncs de prestacion 6ptilll3

MAGNITUI) RIOl6cICA Variaci61l HiologicaCVt>; 0 /....

...:specifi~dont.'S 61JlilllaCI/.(%) £5.(%) ET.(%) ETa(~)

P<O.05 P<O.OI

Snn-A Ian ina-allliTlOlr.msferasaSnn·BilirrubinaSrrn-Bilirrubina eSlerilicadaSOil-Creal ina-cinas;.Srrn-HierroSrl1\-Trig Iicerido

2211 Qufmica Clinic;. 2000: 19 (]l

2·U -1.1.625.6 30.536.8 43.222.8 -1.0.026.5 23.220.9 37.2

6.16..9.25.76.65.2

6.05.07.15.8H5.3

16.015.522.315.215.31-1..0

20.219.928.519.019.817.5

ANEXO IV. Rcfcrcncias bibliograficas para cada magnitud biol6gica.

Magnitud Hiologica

Srrn-Il-DcsoxicortisolSrrn-17-HidroxiprogcstcronadUri-4-hidrox i-3-metoxirnandelato (V MA)Srrn-5 'NuckotidasudUri -5-H idrox ii ndol acctato,concelllracionSrm-Ct l - Antiqui 1ll00ripsinuSrlll-ct.,~Ant itripsinuSrm-Ct,-Glicoprotcina acidaSrm-Ct,-l-GlobulinaUri -Ct,-M icroglobulill<l. concentr<lci6n.prirncra micci(JIl

Pla-a2-Anl iplasm inaSrt11-Ct~-Globulina

Srrn-al-Macroglobul inaUri-o.2-Microglobulina.llujo.primcru micci6nSrm-a-Amilasa

Snn-et-Amilasa pancrdticaUri-et-Amilasa. conccntr;.ICi6n. aleatoriaSrm-o.-C'lrotcnoPac-Aclaramiento de crcatininioSrlll-Adenosi na-desaminasa(San)Pqs-Adrenal inaPhl-AdrcnalinaSrm-AguaSnn-AlanilW-aminopcptidasaSnn-Alani na-Ul11 inotransfcrasa

Srm-Albllmina

Uri-Albumina. conccntracion.primera miceionSrm-AldostcronadUri-Aldostcrona. eonccntraci6ndUri-Amonio. f1ujoSan-Amplitud de distribucioncritrocitariaSan-Amplillld de distribucion plaquctarSrm-A ndrostcndionaSrm-Antigeno CA 125Srm-Antfgcllo CA 15.3Srm-AmfgelloCA 19.9Srm-Antigcno CA 549Snn-Antigeno c,m:inoembriollarioSrm-Antfgcllo cspccilico dc la pr6stalaSrm-Antigcllo MCSrm-Antigello polipcplidico lisular (TPA)Srm-Allligcno polipcptfdico lisularespccflico (TPS)Srm-Anlfgeno SCCPia-Aillilrombina IIISnn-Apolipoprotefna A I

Snn-ApolipoproteilW II

Srm-Ascorbato

Referenda

136. 137136. 13713390. 112

1332484,95. 15324.95, 15390.92

105

2690,9284.95. 153

10527.30,49.72.90.138. 13930.8230

"'6590202049.857127.46.71.90.138.139.153.161. 166.

16'24.27.37.45.46.47.49.53.62.64.69.72. 84. 9{). 92.110.130.138.139.161. 166, 167. 168

78. 80. 86136. 1371336

28. 34. 88. 10228.88136. 13716.10958.59.76.151109,132.1621616.58.59.76.109.15116,12618,76109. 151

10910922. 26. 106. 15913.21.44.49.93.104.107.120.121.141. 164.13.44.49.93.104.120.121. 141. 16453

Magnitud Biologica

Srm-ASpartalo-am inOlransfcr.lsa

Srm-Ct-TocoferolSrlll-Ih-M icroglobul inaSan-Bus6filos. reeucntoSml-13-CarmcnoSrm-13-CriptoxantinaSrm-13-GlobulinaSrm-Bilirrubina

Srm-Bilirrubina eSlcrificaduSrm-Calcio

dUri-Calcio, conccntraciondUri-Calcio. nujoSnn-Captucion de lriiodolironinadUri-CatecolaminasPla-CislcfnaSrm-Cloruro

Pla-CobreSnn-Colcslerol

Srm-Coleslerol de HDL

Srlll-Coicstcrul de HOLtSrm-Colcstcrol de HDL2

Srm-Colcslcrol de HDL3

Srm-Co1csterol de LOL

Srm-Colesterol dc LDL (metodo dirccto)Srm-Colesterol de VLDLSrrn-Coli Ilestemsa$rm-Co1ineslCrasa. ,letivid;ldSrm-Colineslcrasa, innwnorrcactivaSrm-Componemc C3 del eomplemcntoSrm-Componcntc C4 del eomplemenlO(San)Ers-Conecnlraci6n corpuscularmcdia de hcmoglobinaSrrn-ConisolSrm-Creat ina-ei nasa

Srm-Crcatina-cinasa 2

Referenda

27.69.71. 90.138.139.153. 161. 165,166.167. 16853.117242li. 88. 15453,98.117

"'90.9227.49.64.90. 130.138.139.161. 16690.13927.37,45.46.47.49.52.62.64.66.69.73. 74. 90.110.130. 138. 139. 161.165,166.167. 16863. 140. 149. 15063.66.140.14940133257.27.45.46.47.49.62.64.69.71.74.90. 130. 138. 16 L166,167.16897.52.618. 13.21. 23. 27. 32.39.44.49.50.53.60,69.72. 74. 77.90,93,94. 100,104,107.108.114.120.121. 138.139.141.142.147. 148. 153.158. 161. 163. 164,165,166.167.1688.13.21. 23. 32. 39.50.53.60.72.74.77,93.94,104.107.108.114.120.121.141. 147. 148.1644413.21. 44. 60. 120.12113. 21. 44. 60. 120.1218.13.21. 39. 50. 93.94,104. 107. 10K114.120.121. 141.148. 164148W. 10871.90.112IIII

95. 15395. 153

34. 4K 96. 102136.137.15327.46.90. 138. 139.145.153.161. 165145

Qufmica Clfnil-a 2000: 19 (3) 229

Magnilud Biologica Referenda Magnilod Riolbgica Referencia

28. 34. 36. 48. 81t96. 15.\11728.36.48.88.15449.82.9021. lO·t 115. 121.12.l117130.131.16038.513X. 5133.37.38.52.61.69. 139. 165. 16833.11633.116122.14528.88.15.\28.36.48.88.154

Sml-Lutcfn:l

Srl11-Llitropina(SanlErs-Magrwsiu(Snn)Lks-Magnesio

Srrn-Magllesio

dUri.Magnesio. conl-entraci6n

dUri-Magnesio. nujoSnn-MioglobinaSall-Monocitos. recucnlo

Sall·Nelllr6fi1os. recuelllo

Snn-LicopenoSan-Linfocitos. rccucntoSrm-Lipa....1

Sllll-Lipoprotcina In)

24.95.101.1531.9.28.34.48.52.88.96.102.1541.9. 28. 34.48. 52.71.74.88.96.102.15434.88. 1022751.9.21.81.90.96.131. 152. 155. 166.16754. 14642.43.49.95.15342.43.49.95.15342.43.49.95.15342.43.4942.·0.4937. 60. 136. 137517.21.31.45.46.41.49.64.69.71.14.90.130.138.139.161. 166. 161. 16803.140.149.1506.63. 140. 14951517.21.31.45.46.47.49.62.64.69.71.n 90.130.138.139.161. 166. 161.168

dUri-lon SOOio. concenllaci6n 63.140.149.150dUri·lon SOOio. nujo 6.63.140.1.19Sml-I~oen7.ima I do: L:tctalo-deshidrogenasa 90. 'IISnn-Isocnzim;t 2 dc 1..1ctalO-deshidrogcnasa 111Srm-l~ocl1zim;t 3 de L1clato·deshidrogermsa 111Srm-Isocnzima 4 de Lnclato-deshidrogenasa IIISrlll-IS(l(:nzinl;l 5 de L:tCI'lt(l-d("~hidrog('nUS(lIIIS:IIl-LaC\1llo 125Srm-LactalO-dcshidrogcnas;\ 27. ()9. 90.111. 131$.

139.153.161. 165.161. 1682Pla-Lactofcrrinll

San-Lcucocilos. recuenlo

dUri·lon POlasio. conccnlraci6ndUri-lon POlasio. nujo(Srln)Ers-lon Sodio

(S'lIl)Lks·lon SodioSml-Ion Sodio

Pla-Homocistl:fnaSrl1l-lnmunoglobulilla ASrm-Inmunoglobulina GSrm.IllmtH1Qglobulina MSrm-Inmunoglobulillas cadena K

Snn-Inmunoglobolinas cadena ASnn-Insulina

ISan)Lks·lon POiasioSnn-Ion POiasio

(San)Ers-Hemoglobina corpu<;cu13r media

Snll-Hidroli>ibulrJto deshidrogenas.1Uri -Hidroli> iprol ina/rn inuto. no(:tUnlaSnn-Hierro (II + Ill)

San-Hemoglobin3

Snn.llaploglobina

San-Hemalocrito27. 90.138.1451457.27.37.45.46.47.49.53.62.64.65.72. 90. 110. 138.139.143.161. 165.166. 167. 16863.65.78.140.149.1506.10.12. 14.63.65.78.140.1494.89.1276899.103221t 88. 15428. 34. 48. 88. 96.102118.136.137118118118872622. 15922. IS\)22. 15926I. 9. 27. 52.13152.9522.26.102.144.159136.137.160166. 16712667.1244. 5. 27.49.52.~.11. 90.110.124.130.138.153.161.165.166. 161. 16861. 124

1627. 37.49. 53. 64.69.90. 110. 130.138.139.161. 165.166. 167. 16863. 140. 1~9. ISO63.66.1"'0.14911931.49.7990.9227. 70. 7J. 90. J3ft139.153.16531.60,129110

16040.13627. 31. 37. 46. 49.60.&).90.138.139.165. 16K

(San)Ers-GllXOS:l-6-fosfalo-l-dcshidrogl:nasa 169Sml-Glutali6n pcroxidasa 29

Srm-G Iicoalb\\rn ina

Srm·Globulina.lOtalSrrn-Globulina en[;rlanlC de hormonasSrlll-Giobulina cnlar..mtc de tiruli>ina (ll~G)

Snn-Glucosa

dUri-Fosfato. concenlr.ICi6ndUri-Fosfato. nujoSnn-FosfolipidoSml-Fructosamina

Snn-y-GlobulinaSrm-y-GluwmillrJnsCcmsu

Srm-Fosfalllsa .l1calin:1 isocn~iI1l1l6sc,l

Srm-ro.~futasa a1calina.

isocnzima placcmariaSnn·Fosf.llo

Snn-FolitropinaSml-Fosfat:l..a adda

Snn-Fosfatasa :kida prosl:ltica. aClividadSnn-Fosfatasa :icida tanrato resistent;:Srm-F(Jsfata.~a alcalina

dUri·Dcsox ipi ridion! ina/creali nina(San)Gas-Di6xido de carbonoPla-Dipeplidil-pcptidasa IVPla-Elastasa

San-Eosioolilos. recuentoSan·Eritrocitos. recuento

Snn-E~tradiol

Uri-EslrJdiolSrm-Estradiol no unido a prolcfnaUri·Eslmdiol no unido a protelnaSrm-Faclores reumaloidcosPhi-Factor V de la coagulacionPhi-Factor VII de la coagulaci6n

PIa-Factor VIII de 1a coaglllHci6nPhl-Fuctor Von WillcbnmdPla-Faclor X de la co.1gulaci6nSnn-FcnitinaSnn-FerrOldd:lS3 (ceruloplasmina)

Pla-Fibrin6gcno

dUri-Creatininio. tlujo

dUri-Creatininio. concenlraci6n

Snn-Cre:uina--einasa 2. aClividad

Sml·Crealina-cinasa 2. masaSnn-Creatininio

230 Qufmica Clfnica 2000: 19 (3)

Magnitud Biologicn

dUri-Nitr6gcno. nuj\l(San)pqs-Norndrcnali naPla-NoradrenalinaSnn-Osmolalidad

Snn-OslcocalcinadUri-Oxalato. concentntci61ldUri-O:ooalmo. nujoSnn-Pcptidil dipcptidasa f\ (ECA)

Snn-Peplido CSan-pHdUri -Piridi nolinalcreatini na. alemori:J.S:m-PinivalO

San-Plaquelas. TeCllenlO

San-PlaqllelocritoPla-Plasmin6gcooSrm-PrealbUmirm

Srm-Prol<telinaPla- Prol ilcndopeptidasaSnn-Proptplido C-tcrminal

procolagcno !ipo ISml-Proptplioo N·lemlinalprocolageno tipo ISnn-Proteilla

Pla-PTOlc1na C

Srlll-Proleina C re:lcli':lPla-Proteina <;:

Sml-PrOlc1na tOlal glicadadIJri-l'roteilla. COllL-entm..;i6ndUri-Prmdna.l1lljoP:lc-Rcabsorci6nwbul:lrdc fo~fato

(San)Lks-Rcceptor dl' intcrferonSan-Rcceptor LDLdd RNf\mSrm·RClilllll

Pla-SelcnioSan-SclcnioSnll-Sulf:llo <I<,: l)c~hidrocpiml(!n"",lcmna

Slln-Supcru:<illo dblllul;r,:1Snll-Tc1opeplido C-h:nl1il~lI L'U!(lj,'l,;110 lir.,) 1

Uri-Telopeptillo C 'll'nninal c.\I:\genolipo Ilcre:llinina. primcra micci6uUri-TclopCptido N-termin:ll ct,lagenotipo Ilcrc:Jlinin<l. primera micci6nSI\1·TeslO~terolia

Snn-Te~lo'teron:1

Uri-Te~losleron:l

Srm·Tesloslcrona no unida a proleinaUri-Testosterona nounid:1 a proternaPla-Tiempo de protrombin<l

Pla-Tiempu detrombopl:L'lina p:lrcialSnn-TiroglobulinaSnn-TirOiropina fTSII)

Srm- firoxina

Sml·Tiro,ina no unida a protcllla

Snn-Transferrina

Referenda

62.2.49. 8j-1.5,67.1243341136. 137684.512518. 34. 48. 88. 102.1>128.l)82624136.13799. 103

67. 156

6727.37.49.53.6-1.69.72.90.95.130.138.139.161. 165,166. 167. 16S

22.10624. IIIl<i31140.149. ISO140.149665612853. 1179797136. 1372'.1.5267. 156

55.67.89

89. 135160118.136.137.160118118

11826.35

22. '26. 3540.13715.17.19.40.90.134. I}6. 13715.17.19.17. 40.75.91. 134. 1.36.137.16515.17.19.13427.52.70.95.153

MagnitUfl Uiologicll

$rm-Tr:msferrina deficientcCll carbohidrmusSrm-Triglictrido

Snn-TriioOOlilUllina

Srm-Triiodolironina no unida a protefnaUri-N-f\Cclil Gluc0'<30linidasa.

coocentrJd6nUri-N-Acetil GIlti;v:':lminid~.nllJ\)$rm-L!r,l10

dUri-Urato. conc.:nlrJ.ci6ndUri-L!rato.l1ujo

Srnl-Urea

dUri-Urc.a. <-"(m~ntr.tCi6n

dUri-Urea.l1uJo(S:lIl)F.,r<;·VolunK.'n corpu,t,.'ul:lr 1l1.odio

(5.111)l>q~- Volumen plaquctar medio

Snll-7ea'antina$rm-Zillc

Phl·Zinc

Rererencia

7.8.13.21. 27. 32. 39.-19.50.53.60.72.74.90.93.94. 10·.1.107.108.120.121.138.139.141. 1-t8.153. J61. 163. 164.165

15. 17. 19. 27. .JQ.

75.91. 134.136. 13715. 17. 19

83. 1571577.2;.37_ 53. 69. n.90.138.139. lb!.165. 166. 167. 1681-10.149.150140.1497.27.37_45.46.47.49.6-1.69.72.90.130,138.139.161.165. 166. 167. 16863.140.149.1506.63. 1<10, 14934.48. 70. 88. 96.10228.88.10211752.57.6\97

0ll1111i~aC1inil,"a100f): 19('1 231

ANEXO V. Relacion de llrticulos utilizados pam elabomr hi bllse de dlltOS

I. Ahluwalia N. L:1l1111i-Kt.-cfe CL.Hale~ NR. Heard lL. Da~­

to-doLy \'ariation in iron-~t;Ltu~ indexe~ in cldcrl~ women. AmJOin NUlr 1993: 57: ~ 1~-9.

2. Antonscn S. The e~timatitlnof biolo1,!ieal and pn::malytical\:lriations of inn:lmmation marken.. S:ln J Clin Lab In\ e~t199~: s..- (Sup 219): 55-9.

3. Balehin ZE. Mo~~ PA. FrJ~er CG. Biological \'ariation ofurinary oxalate in different ~pecimen type~. Ann Clin Bio­chcm 1991: 28: 622-3.

~. Heck lensen IE. Sorensen HA. Kollerup G. len.\en LB. So­rensen OH. Biological variation of biochemical bone mar­kers. Scan JOin LIb Ilivest 1994: 54 (Su]1219):36-9.

5. Beck Jensen et al. A single me:Jsurel1lerl[ of bioehemi('alm:lrkers of bone turnover h:Ls limited utility in the individualpc~n.. Scan 1 Clin L:lb In\'e~t 1997: 57: 351-60.

6. Hingham SA. William~ R. Cole n. Price CPo Cumming~

IH. Reference values for analytes of 24-h urine (·olkc­tions know 10 be complete.. Ann Clin Hiochelll 1988: 25:610-9.

7. Biosca C. Ric6s C. limenez CV. Lauzurica R. Galim:ln~ R.Model for e~tablishing \ ari:Jtion in non-healthy "ituations:renal posllrJnplantmion data. Oin Chcm 1997: ~3: 11 2206­,.

8. Bookstcin MS. GiOoJing 5. Dono\'an M. Smith F. Day-hl..day va­nability of scrum cholesterol. tngliceryue. :lIlU high-density lip;:).protein cholesll:rol lewis. Arch Intern Med IWO: 150: 1653-7.

9. Borel MJ. Smith SM. Derr J. Ik:Lrd lL. D:ly-to-d:lY \'urimionin iron-status indices in healthy men and women. Am J ClinNutr 1991: 5~: 719-35.

10. Boylc CEL. Cummings ST. Fmser CG. Amyla!>C \e~us lipa­se aeti\'ity assays: con~ider;lIions from biolo~ical \ariation..Ann Clin Biochcm 1987: 2~ (suppll ):37-8.

II. Brock A. Immunorcacth'e plasma choline!>ler.l'C substanceconcentration_ compared \\ith choline"tem!>c activity con­centration and albumin: inter- and imr:l- individual varia­tions in a he:llthy population group.. 1 Ctin Chem Clin Bio­chem 1990: 28: 851-6.

12. Brock DA. Gantl.~·r ML.lntraindividual v:lriation in 24-hrcreatinine eXl,Tetion and 2~-hr urinary volullle. Clin Chem191'7; 33: 1033.

13. Brown Spcncer A. Boerwinklc Eric. Kashanian Fran k..Swanson NalK·y. ;lI1d p;lt~ch Wolfgang. Vari:Jtion in COlK"Cn­lr:ttions of lipids. lipoprotein lipids. and apolipoproteins A-Iand B in plasmu from he:lhhy women.. Clin Chelll 1990: 36:207-10.

14. Hrowning MCK. Biolo~ical \ariation of the breast-tumourmarker CA 15 3: implicutiotb for nct:e~sary 'tundanb of per­formance and thc imerprelalion of rc!>uit\ , Ann Clin Bio­ehem 1987: 24 (suPPIJ: 35s-8s.

15. Browning MCK. Armlytical goals for quantities u!>Cd to a~­

".;:~s thyromdabolic ~tatus. Ann Oin Biochem 1989:26: 1-12.16. Browning MCK. McF:lrlane NP. Horobin 1M. Preece PE.

Wood RAB. Objective interpretation of re~ult~ for tumourmarker. J NU('I i\'kd Allied Sti 1990: 34(supplj 81),,-\)ls.

17, Browning MCK. Furd RI', C:t1I:lghan 51. Fr:lser CG. Intra­and interindil'idll;i1 biological variation of live :lIwlytes usedin assessing thyroid functiun: implications for necessarystandards of performance and the interpretation of re~ults.

Clin Chem 1986: 32: 962-6.18, Browning i\'ICK. McFarlane NP. Horobin JM. Preece PE.

Wood RAB. E\aluatitlll of the comparati\e clinic:11 utlity ofCAI5.3 and mucinou!> carcinoma-assot:iatcJ antigen C\ICA)in the management of brea.\t carcinoma. Ann Clin Biochelll1988: 25. (suppl): 54~-6s.

19. Hrowning M:lrgarct C. K.. Bennet William ro.'l. Kirbldy Ali-

~n 1. lung Rolund T. Intra-indj\ idual \ ariation of th~ roxin.triiodoth)ronine. :llId thyrotropin in traeted h~pothyroid pa­tient: implicalion" for monitoring rcplaccmem ther.Jpy.. ClinChern 1988: 34: 695-9.

20. Ca~ten~en E. Yudkitl S. Platelet c:ltL'Cholamine concelllrJ­tion" after ~hort·term ,t) re~s in normal ,ubjeb. Clin Sei1994: 86: 35-~ I.

21. Chal1lblc~ LL E. ~kMahon RP. Bmwn SA. Palsch W. I-Ici~,.,

G. Shell Y. Short-term imraindi"jdu:i1 v:lri:lbilit)' in lipopro­tein measurement,: the atherosclerosis risk comlllunities(ARICl study. Am 1 Epidemiol 1992: 136: 1069-81.

22. Clmmbkss Ll E. J'v1cMahon R. Wu K. Folsom A. Finch A.Shen Y. Shor\-lerrn intrailldividual vuriability in hemOSlUsisf:LclOrs. The ARIC study. Ann Epidemiol 1992: 2: 723-33.

23. Choudhury Na~",rin. Lyons Wall Phillipp:L 1\'1.. Stewart Trus­\\ell A. Effc(·t of time bct\\een mea!>urements on within­subjet:t \'ariabilit~· for lO(al cholesterol and high-density lipo­protein cholesterol in .... omen .. Clin Chelll I99..L,{0:7I 0-5.

24. Clark GH. Fra!>CrCG. Biological \:lriation ofacutc phaseprotein~. Ann Clin Hiochern 1993: 30: 373-6.

25. Cobbaert C. Arenben JC. Mulder P. lloogerbrugge N. Lin­de mans J.. Significuncc of variou.\ p:lnlllleters derivcd frombiological \ arjabilit)' of lipoproteina (a). homocysteine. c)'s­teinc and lOtal antioxidant status. Clin Chem 1997:43: 1958·64.

26. Costongs GMPJ. B:ls HM. JanSotl PCW. Short-term :md longterm intr:l-individu:11 I':lrimions and critical differcnees ofcoagulatioll parameters. 1 Clin Chern Clin Biochel11 1985:23: ~05-IO.

27. CoslOng!> GMPI. Jan~on PCw. B:l~ BM. Short-term andlong-term illlrJ-indh idual \·ariations and nitical differencesof clinical chcrnic:lllabor.Jtory par.JulCters. 1 Clin Chern ClinBiochem 1985: 23: 7-16.

28. Costong~ GMP. Jan!>On Pew. Bas 11M. Hennans J. Bromba­cher PJ. Wen-ch JWJ. Short-ternl and long-term intr.J-jndi\'j­dual vari:ujons and critical differcnce~ of haematologicalla­boratory p:lrameter~.1 Clin Chem Clin Biochern 1985: 23:69-76.

29. Covas M1. Coca L. Ricos C. M;lrrugat 1. Biologkul variationof superoxide Disnwtase in erythrocytes and Glutathione pe·roxidase in whole blood. Clin Chem 1997 43: I0 1991-3.

30. Cummings ST, Fntser CG. Totul amylase :llld P;ll1Cfeatic iso­amylase in ~erurtl and urina:con!>iderJtitms from data on bio­logical variation. Ann Clin Biochem 19!19: 26: 335-~0.

31. Da\'ie SJ. Whiting KL. Gould BJ. Biological \'ariation ingl~cated protein!>. Ann Clin Biochem 1993: 30: 260-4.

32. Demacker PN. Schade RW. Janscn RT.Van·, Laar AV. Inlr.J­indi\·idual \ ariation of serum choleslerol. triglycerides andhigh den..it)' lipoprotein cholesterol in normal humans. Athe­rOS(.'lelmi~ 1982: 45: 259-66.

33. Ojurhuu~ 1\'IS. GrJm J. Hylwft Peten-cn P. Klitgaard NAH.Bollerslc\' 1 Heek-Nielscn H. Biological variution of serumand urinary magne.\lum in :Jpparcntly healthy males. Scand JClill Lab lnve~1 1995: 55: 549-5!':.

34. Dot D. Mir6 1. F\lenles X. Within-Sllhjeet biologic;i1 v;lria­tion of hernatlllugicalquantities :md :u1:lIyti~'al go;i1s. An.:hPathol Lab Med 1992: 116: 825-6.

35. 0010. Mir6 J. Fuenle~-ArderiuX. Within-subject andbetween-subject biologicul \'ariation of prothrombin timeand acth'ed p.1nial thrombopla~tin time. Ann Clin Biochem1992: 29: ~22-5.

.l6. Dot D. Mir6 1. Fuentcs-Arderiu X. IJiological variation ofthe leuk()l,.'~·le differential count quantities. Scan 1 Clin Labl11\cstl992:952:607-11.

37. 8:kfeldt J.Chamble!>s L1. Shen Y. Short-term. Within-Pe~n

VMiability in Clinician Chemi~try test rcsulls. Arch PatholLib Med 1994: 118: 496-500.

38. Elin Ronald J. Hosseini Jeanelle M. Ruddcl Mark. Illlraindi­vidual variability of blood magnesium parameters withtime. Clin Chern 1989: 35: 111~-5.

39. Elveback LR. Weidman WHo Ellefson RD. Da)·-to-day va­riabilily and Analytic error in delerminalions of lipids inchildren. Mayo Clin Proc 1980: 55:267-9.

40. Feldt-Rasmussen U. Petersen PH. Blaabjerg O. Horder M.Long-term \'anability in senJm thyroglobulin and thyroid reolated hormones in healthy subjecis. ACla Endocrinologica1980:95: 328·34.

41. Fogany Y. FraserCG. Browning MCK.lntra· and inter-irldi­vidual variation of serum angiotensin convertingcnzyme:c1inival implicalions.. Ann Clin Biochem 1989: 26:201-2.

42. Ford RP. Mitchell PEG. Fmser CG. Desirable performancecharacteristics and clinical utility of immunoglobulin andlight-chain assuys derivcd from data on biological variation.Clin Chem 1988: 34: 1733-6.

43, Ford RP. Mitchell PEG. Fraser CG. The dinical utility of kand I light-chain assays: considerations from biological va­riation d,Ll;L. Ann Clin Biochem 1988:spI42S-143S.

44. Ford RP. Essential dUla derived from biological varialion forestableshmem and usc of lipid analyses.. Ann Clin Biochem1989: 26: 281-5.

~5. Fraser CG. Hearne CR. Components of \'arianee of someplasma conslilucms in patiens with myocardial infarclion.Ann Clin Biochem 1982: 19:-02-4.

46. Fr.Jser CG. Williams P. Shon-Ierm biological \'ariation ofplasma analytes in renal disease. Clin Chern 1983:29:508-10

47. Fraser CG. Hearne CR. Components of \'ariance of SOllleplasma eonslituents in paliems wilh myocardial infarction.Ann Clin Biochem 1982:19: 431--1.

48. Fraser CG. Wilkinson SI'. Ne\'ille RG. KnOll JOE. King JF.MacWallcr RS. Biologic varialion of common hemalologiclaborJtory qu:mtilies in the clderly. Am J Clin Palhol 1989:92: ~65-70.

49. Fraser Callum G. Cummings Steven T. Wilkinson Stephen P.Neville Ronald G. KnOll James D. E. Ho Olg". and 1\bcWalterRonald S. Biologicul variability of 26 clinkal chcmistry analy­tes in elderly people. Clin Chcm 19119: 35: 783-6.

50. Friedlandcr Y. Kilrk JD. Stein Y. V"riability of Plasma Lipidsand LipoproLeins: ThejerUSlllcm Lipid Research ClinicStudy. Clin Chcm 1985:31: 1121-6.

51. Gallacher RE. Browning MCK. Fra~er CG. Wilkinson SI'.MllcLenn:lll \VJ. A mcthod for simultaneously estimatingplasma. crythrocyle and leukocyte sodium. potassium andmagnesium: reference values and considerJtions from biolo­gical variation d"ta. Clin Chern 1987: 33: 1326-30.

52. Gallagher SK. Johnson LK. Milne DB. ShorHerm and long­teml \'arillbility of indices relaIL-d to nUlritional ~Iatus. I: Ca.Cu. Fe. Mg. alld Zn. Clin Chern 1989: 35: 369-73.

53. Gallagher SK. JohnsooAK. Milne DB. Short and Ioog term \'a­ri:lbilily of sckctcd indices related to nutrilional SlalUS. 11. Vita­

mins.lipids. and proIcin indkcs. Clin Chcm 1992: 38: 1~9-53.

5~. Garg Uc. Zheng ZJ. Folsom AR. Moycr YS. Tsai MY. ~k­Go\'cm P. Eckfc1dt JH . Short-Ienll and long'lenn \'ariabilit)'of plasma homocysleine. measurement. Clin Chern 1997; .J]:

141·5.55. Garnero P. Delmas PD. Vuri"bility :md respoll~e of urinary

resorption llI:trkcrs to hormone replaeemclllthcr:Lpy . J BoneMincralL~cs 199:14:470-1.

56. Gerdes AM. Hul10ft Petcrsen P. Hurder i\t Bonncvic-Niel­sen V. Separatc cstinwlion 01' biologie:i1 and ,lIwlytical va­riance components when quantities and reagcnts arc unsta­ble. SC:ll1d J Clin Lab Invest 1995: 55: 523-li.

57. Gilcs L Smicklas-Wright H. Fosmire G. DeIT J. Variationsin plasma zinc in older rJJl:n and \\omen. Biological TraceElement Research 199-t: ~I: 235--13.

58. Gion M. Cappelli G. Mione R. Pi~torello 1'..\' I\-IcQ S. VignaliG. Fonunalo A. Saracchini S. BiObioli R. Giuli<;ano 11..1 . E\"a­luation of crilical differences of CEA and CA 15.3 lc\cls inlIerial samples from paliems opl:rJtcd for breasl cancer. Inl JBioi Marke~ 199.4: 9: 135-9.

59. Gioo M. Cappelli G. Miol"lC R.. Vignati G. Fonunalo A. Sa­racchini S. Biasioli R. Giulhano 1\1 . Variabi'it~ of IUmormarkers in the follow-up of patienb r.!dicall) re".,~·ted forbrea.~1 cancer. Tumor Bioi 1993: I~: 325-33.

60. Go(blang IF. Illlra-indi\·idual \ariation: ~ignificant change~

in par.!mcters of lipid and carboh~drJtc metabolism in Iheindividual andintra-indi\'idual \'ariation in difl"crent te~t po­

pullLlions. Ann Clin Biochem 1985: 22: 618-2~.

61. Gonzalez-Revalderia J. Gllrda-Berl11cjo S. Menchi'n-Hem:­ros A. Fern:indez-Rodrigucz E. Biological varialion of Zll.Cu. :md Mg in serum of hcalthy subjects. Clin Chem 1990:36:2140-1

62, GOllz:i1cz-Rc\'alderia J. Garda-Bermejo S. 1'.'knchcn-He­Hero.~ A. Fernandez-Rodriguez E. Towurds nUHoweranalytical goals in routine I:lboratory work. Clin Chem1991: 37: 596.

63. Gowans Ei\'IS. Fraser CG. Biological \':lriation in analyleconcelllrations in urine of apparcntly health)' men and wo­

men. Clin Chem 1987: 33: 8·n-50.6-t. Gowans EMS. Fr.!scr G. Longer-tenn biological \"ariation of

commonly anal)'zed ~erum con~lituenls. Clin Chcm1987:33: 717.

65. Gowans Ei\'IS. Fraser CG. Biological \ ari;LIion of SCnJm andurine creatinine and erealinine c1carance: ramificalion~ forinterprel:ltion of resuhs and patient care. Ann Clin Biochem1988:25: 259-63.

66. Go",an~ MS. FraserCG. Do bioloA;il·a. \'ariation data shedlight on lhe demise of some hi~loriclLl indiec-s uscd 10 as~~calcium homcost"sis? Clin Chem 1987:33:1267-8.

67. Bannon R. Blumsohll A. N:l)'lor K. E:1_"lell R. Respon.'oC ofbiochc-mic,ll markers of bone turnovcr to hormone replace­mCnl them)))': impact of biologicul \'ariabilily. J Bone & Mi­nerai ~es 1998:13:1124·33.

6X. l-hLrding I'J. Fraser CG. Biological I'ari:ttion of blood acid­base .~taLUS: Con.;cqucru:es for an:i1ytic,L1 goal-sclling and in­tcrl'ret:llion of results. Clin Chelll 1'187;33: 1416-R.

69, Harris EK. K:mofsky 1'. Shukarji G. CotlO\'e E. Biologicaland analytic component!> of \·"r1o.tion in long-term studies oflIenJ11l constitucnlS in normal subjCl·b. C1in Chem 1970; 16:1022-7.

70. Helander A. VabO E. Le\"in K. Borg S. ImrJ-and imenndid­dual "ariabilit)' of carbohydratc-dcficient tr.!nsferrin. G-glu­lamyhl"Jnsfcrase. and mean corpu"cular volume in tecIOla·len.. Clin Chem 1998: oW: 2120-5.

71. HUllei WGE. ImrJ-indi\ idual \ anation of anlLl)·tc-S in 1>CnJrnof p:llients \':ith chronic li\'cr di!>Ca!>C". Clin Chem 1987: 33:1133-6.

72. HOIzel WGE. Intra-indi\ idual \ :lrialion of sonl(' anal)'le~ in!oi.'llJm of paticnls with in"ulin.depcndelll diabetes mellitu".Clin Chcm 1987: 33: 57-61.

73. HOIzel WGE. IntrJ-individual wrialion of MJme :mal)'tc," in~erum of puticnts wilh chronic rerHl1 failure. Clin Chem19K7: 33:670·3.

74. I-Wlzcl WGE. Influcnce of hypcrten~ionand :H1tihypcrtcn"il"edrugs on Ihe biologic,L1 imr;L-indil'idu,,1 variation of electroly­tes:md lipids in SCl"\L1n. Clin ChclII 1'18R: 34: 1485-8,

75. I-liilzcl WGE. Dcsehncr \V. Intra-individual \'llri,nion of se­nun thYlo.~in ,LIld Lriiodothyronine in pregnancy. Clin Chem1988; 34: 2063-5.

QuimicaCiinica2000: 19(3) 2_B

76. Uolzel et al.. Individual reference range~ of CA 15-3. MCAand CEA in recurrence of breast cancer. Scan J elin Lab In­\e;;t 1995:55 (sup 121): 93-101.

17 lIowes LG. Krum U. Inlra~individual variabilily of plasmacholesterol concenlralions. Clin Chem 1988; 34: 1930-1.

78. Ho"ey JEA. Browning MCk. Fmser CG. Is ('arly morningspot urin.,ry albumin C"Q1\(:entrJtinn the beM ffiCJnS of estima­ling albuminuria'!. Ann Clin Biuchem 19R7: 24 (Suppl):127·8.

79. Howey JEA. Browning MCk. Fraser eG. A~say of scrumfl'ut·tos<Jmine that minimiles standardiz:lIion and matrix pro­blems: us..' 10 :I~~es com(.Kmenl.s of biological \ ariation. ClinChem 1987; J): 269-72.

80, Ilowey JE.Browfliflg MC. Fraser CG. Selectifl!; the optimumspecimen for asst.'Ssiflg slight albuminuria. and a slrategy fOfclinical invesligation:nO\'C! uses of data on !.'iological varia­lion. Oin Chem 1987: 33:2034-8.

81. lioyer K. P11)'siologic variation ill the iron conlelll of humanblood serum. Acta Med SC:lt1l11944: 119: 562·82.

82. Huguet J. Fucnte~-Anleriu X. lJiological vat'i:l1ion in thecat:llylic concentration of pmlcreatic alfa-amyl:lse andtri:ll.:ylglycerollipasc in ,crul11. SC<Jnd J Clin Lab Invcst1991:51: 735-1t

83. Iluguet J. Fuentes-Arderiu X. Ferre C . Imr:lindividual Bio­10gic<Jl variatlon in the N-at'ctyl-hcla-gluco':lIninidase!crea­lillinium ratit. for firsl llIoming urille. Clin Chern 1989: 35:1256.

84. l-lyl!Ofl Petersen P. FcItJt-Ra'musseli U. HordeT M. Bla­al>jerg O. Thygc~en K. Variability of plasma proteins ac­"odillg to molecular sizc. Long.term and ,horl-term in­tra-i11l1ividllal v:lrlntion. SC:11l J Clin Lab Invcst IIJ81: 41:14~-50.

85. J:lhan A. Browning Margaret CK. Fr:lser eG. Drsi­rable pcrlomancc ,t:llld:lrds for assays of ~erum watcr andosmolality. Clin Chem 1988: 3-1: 995.

86. Jens.:-n JS. Intm-individual variation of overnight urinary al­bumin eltcrelion in clinically heallhy nliddle-aged indivi­duals. Clin Chirn A'-la 1995; 2-13: 95-9.

87. Jimenel CV . UM'fulnc!>s of «'fcrenee limits and c\'aluationof ,ignific:UI1 diffcrence~. All c~:lIl1vle uf the biological V:l­ri,llion of ~cnlln rhCUllwlnid f,Klors_ Ann BioI ClinilltlC1~)1)-I: 52: .'i:!lJ-]J.

88. Jimcllcl CV. Variabilidad biol6gica inlmindividual de la~

magniluL!t·, "ilolwm:ltol(,gicas C0l110 ohjeli.·o dt· CilliJ<Ju:1I1alftica. Qllim Clin 1992: II: 1'17-50.

R9. JI1 I-IS. Brown LB. Stringer 1\'IA. Ldgh C. Schcm:r C. She­l):trd K. Jrnkin' D. Knu!>Jcn J. Cannon R. Compari~on ofim:ll~ tical pcrrormenee :md biological \'ariabilily of lhreeNme revlrption a~~ays. (lin Chcm 1097;-13: 1570-6.

90_ Juan·Perdra L. Variabilitat biologica il11raindhidual de lesmagnitudt" hioqtlimicpl(~'. Alllieacions clini(IUes. DoclUr:11Thc~is. BarcelOl1a UniH'r.,ity 11)89.

1)1 J\I<lll"Pel'cir,1 I.. N:II':m'l> MA. ROCH M. FU~'lltcs-Al'Jeriu X.Within.'ubject v:ld:nion Ill' thyro:l.in and triiodothyronineconcenlrali.m in 'cmltl. Clin CI1l'J11 19'-) I: 37: 771-].

92. Juan-Pereira L. Fucnle~-Arl1crill x. Intra·lndividual Va­riatiC>ll or the Elcclre>phort,tic SCrulll PrOll'in FT:lclion". Clin(he'n 1989.35:15J4.

(J3. Kafol"lCk SD. Derby CA. Bachorik 1'5. Biologil-al v:lriabilityof lipoprotcins :lnd apolipoprutein" in patient referred to a li­pid clinic. Clin Chem 1992; ]X: 86-1-71.

9-1. K:lfonek SO. l)0110van L. Lovejoy KL. Ilnchorik I'S. Biolo­gil-al variation of lipids and lipoproteins in fin£erslick bllXld.Clin Chern 19%:42:2002-8.

\)5. Li:lppis N. Fuchs R, Rcimnitl. P. Physiologische Sehwan­lUllgCll tler Konlentrationcn von Ges:ul1\ei\\cib. Twnsferrin.Ilaptogiobin. saurem :llfa I-Glycokprotein. alfaZ-M:lkroglo-

2\.-1 Quim'c.lChllie:l2000: 19l3)

bulin. Properdin Faktor B. C3-Komplement_ C4-Komplc­mel1l_ IgA. IgG. IgM. alfa l-amitryp-;in und Cocruloplasminin Nuchtern~erum ge"uncJer Manner. Arttl Lab 1986: 32:286-92.

96. Looker "C, Sempo CT. till K. John~on CL. Gunter EW.Within-peNln variance in biochemical indicalnrs of iron sta­tus: effeels on prevalence estimales. Am J Clin NlIlr 1990:52: 541-7.

97. Lu~ O. Naidoo D. The :ls~esmcnt of biological variiltioncomponents of l.:opper. line. lind selenium. J NUll' Biochcl1l1995: 6: 4.1-7.

98. Lux O. Naidoo D. Biological vari:llion of heta·earotene. Nu­trilion Research 199-1:14: 693-8.

99. Maes Michael. Scharpt Simon. Dc Meester Ingrid. Qoos(:nsPhilip. Wauters Annick. Neels Hugo_ Verkerk Robert. DeM('yer Frans. D'Hondt Peler. Peeters Dirk. Schotte Chris.and Cos)'ns Paul. Componenls of biological \'ariation inProl)'1 EllUOpcptid:lse and Dipeplid),I-Pcptidase IV activityin plasnw of he:lhhy subjects. Clin Che1ll 1994;40: 1686-91.

100. Macy EM. Hayes TE. Tracy RP. Variabilily in the II1casura­111,:l1t.. of C- reactivc protcin in healthy subjcts: implic:Hionsfor referent'e in!erval~ and cpidemiological applic:ltions.Clin Cheln 1997: 43: 52-8.

101. Maes M. Coorernan W. Dclanghc J. Scharpt S. WaUiers A.Ned~ H. O'Hondt P. Pt'elers D. Cosyns P. Ranjan R. Bos­man.. E. 1)C~le~er F. Elkis H. Desnydcr R. Component.'> ofbiological varialion in pl:lsma haptoglobin: relalionships topla,ma fihrinogen ami immunc \·llriables. including inter­leukin·6 and its rel:Cplor. Clin Chim Aeta 1995: 239: 23-35.

101. Maes M. Scharp<: S. Cuorcman W. Wauters A. Neels H. Ver­kerk R. Dc Meyer F. O'llondt P. Peetel's D. Cosyns r. COTll­ponen1s of hiological. including .wasonal. variation in hcm:l­IOlngic:iI IIIca~urelllent!> and plasnHl fibrinogenconcentrlltions in normal human... E.\pericntia 1995; 51:141-9.

103. Mac' M. Scarpt S. Dc Meester I. Goossen.. P. Wauters A.Neels II. Werkerk H. Dc Meyer F. D' Hoodt P. Peeters D.Sl.:hOlle r. Cos)'ns P. Components of biological variation inpropil endopeptidase and dipcplidyl-pcptidasc IV activity inplasma ofht'allhy subjcts. Clin Chern 1994; 40: 1686-91.

104. M:lrco.'inaSM. Gaur VP. Alllers JJ. Biological v:lriaubility ofcholeslerol. Triglyceride. low-~Illd high-density lipoproteincholesterol. Iipoprotein(a). and Apolipoproteins a-I lind B.Clin Chem 1994: 40: 57-1-R.

105. Mclla M. Salamone A. Spagliarui G. Slella P. Guagnellini E.Rcrerence valucs :Ind biological varialion for albumin. alral­microglobulin and bcla2-microglobulin in uriune specimens.Biochem Clin 1989: 13 (suppl): 89.

106. Melli d'Eril G. Ane,~i A.Ri1.70 v. Trotti R. Biological varia­tion in I'rtltein C. Prolein S, llnd t\ntilhrombin concelltra­tions in plasma of heallhy subjects. Eur J Clin Chem ClinBiochel11 1997: 35 (-I): 257-260.

IU7. Mj\)s O. Ran S.Bj,",u. Henden T. Theile D,Ftlrde O. MillerN. A longillltlilwl study of Ihe biologienl v:lriability of plas­111:1 lipoprmcins in healthy young adults. AtherosckrtJ~i~1979: ;\4:75-81.

108. Mogadam M. Ahmc.-d S. Mensch A. Godwin 1. Within-per­son nuctuations of serum choleslel'Ol and lipoproteins. ArchInterMl-d 1990; 150: 1645·8.

109. Mom J . Variabilit:u intr.lindividu:l1 deb marcadors tunl()­rals. Donoral The~is. Bareelon:! AUlhonomic Universily1993.

110. IvlorrisUA. Wishart JM. Horowitz M. Need AG. NordinBEe. The reproducibility of tlOne-rel;rtctl biochemical varia­bles in post-menop;ru~al women.. Ann Clin Oiochcm 19\)0;27: 562-8.

111. Moses GC. Hl.'ndl.'r,on AR. Biologic:11 V:lri:lnc(' of '1'01:11

lilc\<lte Dehyurog<:nilse ,iIld Il~ I<;otnl.)'mt"~ ,n {·Iuman Serum.ClinChcm 1984:30: 1737-41.

112. Moses Cc. Tuckerman JF. Henderson AR. BiologkalVilriance ofCholineslerase and 5'- Nucleotidase in Serum ofHealthy Person". Clin Chem 1986: 32: 175-7.

114. MUUSlC J. Intra-individual-variabilily ilnd retesHeabilit)' oflipoproteins in serulll OfcofOlwry artery disease pillients.Ann Oin Biochem 1987: 24(suppl): 136.

115. Nazir OJ, Hill SA. ~kQueen NlJ. Biological variation in Li­popprotein (il). Clin Chcm Lab /I.·led 1999:37:K5.

116. Nicoll CW. Struthers AD. Fraser CG. Biological v;lriation ofurinary magnesium, Clin Chelll 1991: 37: 179-l--5.

117. OlmediJia B. Granado F. Blanw I. Rojas-Hidalgo E. Seaso­nal and sex-relalcd vari<ltio!ls in six serum carolenoids. rdi­nol. and a-tocoph"rol. Am J Clin Nutr 1994: 60: 106-10.

118. Ooi LSM. Pnnesar NS. Masarei JRL Within- ;lnd between­subject variation in, and as~ocintion~ between. sel'um COII­

centrations and urinary exnetion of teSlosterone and estra­diol in Chinese men. Clin Chim Acta 1995: 236: 87-92.

119. Onohi 1. Fuentes-Ardcriu X. Intra and inetrindividualbilogical variation of the serum concctllralion of phospholi­pids. Clin Chem 1991.37: 583.

120. Ortola J. Cilstiiieira M. J, and Fuemes-ArdNiu X. Biologicalvarimion dma applie,d 10 the selection of serum lipid r':lliosused as risk ll1urkcrs of coronary heao diseuse,. Clill Chetll1992: 38: 56-9.

121. Pag<ll1i F. Pilllleghini 1\-'1. Significance of Variou!> Par"rne­tel'S Derived From Biologicill Variability for Lipid and Lipo.prolcin Analyses. Clin Biochem 1993: 26: 415-20.

122. PanteghiniM. Pagani F. Biological \'arimion ofmioglobincin serum, Clin Chem 1997:43:2435.

123, Panteghini M, Pag'lI1i F Pre-anill}'lit"l, atlillylical <Illd biolo·gical soun:es of variution of lilXlpmlein (il). Eur J Clin Chel11Clin Biochem 1993: 31 :23-8.

124. Pantcghilli M. Pagani F. Biological varialion in bone-deri·vcd biochemicill markers in serum.. Scan J Clin Lub Invest1995: 55: 609-16.

125. PUllleghini M. P:lgani F. Biologicul Vilri:i1ion of lact.lte anJPinlVale in blood. Clin Chem 1993: 39: 908.

126, Panteghini M. Pilguni F. BOllora R _Pre-ana!ytic<:ll and biolo­gical variability of proslatic ucid I'hosphata~e Jnd Pro~tale­

Specific Antigen in ~erum from puticnlS with proslalic pUl­holog)' . Eur J Clin Chenl Clin Biochem 1992: 30: 135-9.

127. Puntcghini M. Pagani F. Biological variation in lll'inary ex·crelion of deoxypyridinoline_ Clin Chem 1995:41. S20().

128. Petersen Niels Erik. Kongskov Lilrsen Leif. Nissen ~h:nrik.

Gryesten Jensen Lilli:m. Jensen Alice. Hyltoft Pelersen Per.Horder Mogens. Gregehen Niels. and Kristiansen Karsten.Improvcd Rnase Protection a~SilY for quamifying LDL-Re·ccptor mRNA: estimation of analytical imprecilion and bilo­logical variunce in pcriphcral bk,,:xl mOllonudeurcel1s.. Clin

Chem 1995:41: 1605-13.129. Phi1lipou George. Phillip." Patrick. IlltrainJividual Variation

of Glycohcmoglobi 11: llnplications for l'l1erprelation andAnalytical Goab. Clil1 Chem 1993:39:2305-8.

130. Pickup JF. Hurris EK, Keurns M. Brown SS. Intnl·inJividu;l1Varialion of Some Scrum Constituents and its Relevance toPopulation. based Refercnce Ranges. Clin Chem 1977:23:842-50.

131. Pilon VA, Howanitz PJ. Howanilz JH. Domrcs N. Duy­IO-Duy Vuriiltion in Serunl Ferritin Concentration in HeulthySUbjects. Clin Chem 1981: 27: 78-82,

132. Plebani M, Giacomini A, Beghi L. ~ Paoli M, Rovef<lni G.Gal1eotti F. Cursini A. Fraser CG. Serum tumor markcrs inlllonitoring pUlients: interpreliltion of results using analyticaland biological varialion. Anticancer Res 1996: 16:2249-52.

133. Polo MJ. Ricos C. Jllvany R. Cural,ln R. Aplicuciones de la

variabilld<ld biol(,gica de 110IT:10na~ anali/,.adas en orin". EII­Jocrinologiu 1992: 39: HlI-·i,

134. Polo MJ. Ricos C, CmalJn R. Juvany R. AI)lit'"ci6n clfnicade los datos de variabilidad biol6gica de las hormonas tiroi­deils, Med Ciill 1992: 9'.l: 529-3l.

135. Popp-SnijdefS C. Lips P. NCldho' Jc. Intr.l-individual vuria­tion in bOllC resorption murkers in urine. Ann Clin l3iochellJ1996: 33: 347-S.

136, Rico, C. Arb6s MA. ObjClivos de clllidad pura Ius detcrmi­nucioncs de hormonas. Endocrinologiu 1990: 37:230-3.

137. Ricos C. Arb<h i\·IA. QUillily gOills for honnonc tcsting.. AnnClin Biochcm 1990: 27: 353-8.

138. Ricos C. Codinu R. L;l \ariabilidad hiologica il1tr3individualcom" objeto dc calidad ltnulflica.. Rev Diag Bioi 1989: 38:34-6.

139. Kieos C. Garda-Arumf E. Rodriguiez.Rubio R. Schwartz S.Eficut'ia de un programil imerno de comrolde c;lIidad. QuimClinI986:5: 159-65.

140. Rk6~ C. Jimencz CV. HenH'indez /\. Simon M. Perich C. AI·varez V. Miuchinelu J. Maei:! M. Biological varialion in uri­ne sampks used for an31yte rneasuremenK Clin Chem 1994:40: 472·7.

141. Rivcra-Coll A. Fucntcs-Ardcriu X. f)fcz-Noguera A, CirCa­dian Rhythmic in serum concentrations of dinicaH) impor­tant lipids. Cliu Chem 1994: 40: 1549-53.

142. Robert, SL. McMurry MO. Cllnnor WE. Does egg feeding(Le. dietary <:hoksterol) ilffect rlilsma dwlesterol levels inhumans? The results of a double bind study. Am J Clin Nutr1981: 34:2092-9.

143. ROSilllO TG, Brown HH. Anillytical and Biological Variabilityof Scnun Crc,'liuinc and Cre<itinine Cle"rance: Implicationsfor Clinical llllcrpn:liltion. Clill Cheln 1982: 28: 2.130-1

144. Roscnson RS. Tangney Cc. Hafner H....l. lnlllli'ldi"idual \3­ri;lhility of fibrinogen level~ [,ml cllrdio\'aseular risk profile.Arteri,)scler Thrornb 19')4: 14: 1928-32.

145. Ross SM. Fraser CG. Biological \'ari:ltinn ofcardiuc mur­kers: anulytkul and dinical consictcriltions. Ann Clin Bio­chcm 1998:35: 80-4.

146. Ro~~i E. Beilby JP. McQuillan BM. l·lu1Ig J. Biological \'a­riahiity and reference imcrv<lls for tOlal plasl!lil hom(x;y~tei­

I1C. Ann Clin Biochcm 1999:36:56-61147. Rotterr!3m E£'. Katan [','IB, Knuiman JT. Importance oflimt"

intervill bet ween rt:peated measurements of IOtul or high­density lipoprotcin cholesterol when eSlimatiug an indivi·dual's baseline COllcenlrations. Clin Chern 1987: 33: 1913-5.

148. $chectlllull G. Patsches M. Sasse EA. Variabilily in choleslc­rol lIleaSU!'.I11lenh: <:omparison of cu1culatcJ and direcl LOLcho1c~terol dewfluinatiolls. Clin Chem 1996; 42: 732-6.

149. Shephard IvIDS. Pcnbcrthy LA. Fruser CG Short- andl.ong-Term lJiological \'nriation in Aualyt ..,s in Urinc of Ap­parently Healthy Individuals. Clin Chem 1981: 27: 569-73.

150. Sim6n M, Maci:l M. Ribera C, Alvarez V. Hcm;indez A. ~'lin­

chinda J. Jimcncl Cv. Pcrirh C. RicO;; C. Objeti\"l)C ,maliticosde calidud en las detcrlllinaciones dc diwrsos constituycntes enorinu. Quimica C1init'a 1992: II: I56·6(J.

15!. Sijlctormos C. Schiokr V. Nielsen D. Skovsgaard T. 00111·nerbowsky p, lutcrprctUlion of Rcsults for Tumor Marknsnn tht Basis of Anulytieallmprecision an biologicul \'uria­tiou. Din Chem 19'13: 39:2077-83.

152. Swtl<lnd B. Winkel P: Bukehmd H. Variation ufsenlm ironCOI1('Cl11rmivll in young healthy rnen:within-dil}' und dily 10dil)' changes. Clin Biochem 1976: 9: 26-9.

153. Stutland BE, Winkel P, Killingsworth LM. Faclors Con­tributing to Intru-Individual Varialion of Serum Con~ti­

tuenlS: 6. Physiological D:lY-lO-f);ly VuriutiOI1 in Concentra­tions of 10 Specific Proteins in Sera of Healthy SubjcCls.Clin Chem 1976: 22: 1635-8.

Quimica Clinica 2000: 19 (3) 235

154. Slat land BE. Winkel P. H,lrris SC. Burds,lll i\U. SaundersAM. Evaluation of sources of \'ariation of leukocyte countsand Ol:her hematologic quantities using \ ery precise aUloaledanalyzers. Am J Clin ?athol 1977: 69: -48-~.

155. Stalland BE. Winkd P. Relationship of dllY-lo-day varia­tion of serum iron concenlraiions 10 iron-binding capa­city in healthy young women. Am J Clin Pat hoi 1977:67:8-4-90.

156. Ste\'enson HP. Leslie H. Sheridan B. Intr... -indi\'idual \'aria­tion in serum type I procollagen carboxy-terminal propepli­de and type [ collagen carboxy-tcrminal cross-linked telo­peptide conccntrations. Ann Clin Biochel11 1997: 34: 317-8.

157. Stolarek I. HOlVey JEA. r:rascr CG. Biological variation ofurinary N-acetyl-bcta-O-glucosaminidasc: practical and cli­nic,11 implications.. Clin Chem 1989: 35: 560-3.

158. Thompson SG. Pocock SJ . The \'ariabilily of senlm choles­terol measurement!>: implications for screening and monito­ring. J C1in Epidcmiol 1990: -43: 783-9.

159. lbompson SG. Manin Jc. Meade nv. Sources of \'ariabilil)'in coagul,uion factor assays. Thrombosi:. & Haemoslasis1987: 58: 1073-7.

160. Valero-Politi J. Fucntes-Ardcriu X. Within-and BCllVeen­Subjcl Biological V,lri,llions of Follilropin. LUlropin. Tesles­terone.and Sex-Ilinding Globulin in men. Clin Chern 1993:39: 1723-5.

161. Van Steineghem AC. Robertson EA. Young OS. VarianceComponents of Serum Constitucnts in Heahhy Individuals.Clin Chclll 1978: 24: 212-22.

162. Veslerg,lard EM. Hcin HO. Meyer H. Grunnet N. JorgensenJ. Wolf H. Ornlufl TF. Reference \'alues ,md biological varia­lion for lumur marker Ca 19-9 in serum for different Lewis

D(, Qufmica Clinica ~()I)(): 19 (3)

and sttrelor genotypes and evaluation of secretor and Lewisgenoyyping in a caucasian population. Clin Chem I999: 45: 54-61.

163. Warnick GR. Albers JJ. Physiological and analylical varia­tion in choleslcrol and trigl)·cerides. Lipids 1976; II: 203-8.

164. Wasenius A. Slugll,ud M. Ollerslad JE. Fro)'sho\' 0_ Diurnaland monthl)' illlra-individual \'ariabilily of the concentrationof lipids. lipoproteins and apoproteins. Scand J Clin Lab In­vesl 1990: 50: 632--42.

165. Williams GZ. Widdowson GM. Penton J. IndividualCharacter of Varialion in Time-Series Studies of Healthy Pe­oplc II. Differcnces in Values for Clinical Chemical Anal)'tesin Serum among Demographic Groups by Age and Sell. ClinChem 1978: 24: 313-~O.

166. Winkel P. Stlltland BE. Bokelund H. Faclors Contribuling 10Intra-Individual Variation of Serum Constituellls: 5. Shon­Term Day-to-Day and Within-Hour Variation of Serum Cons­tilUenls in Heallhy Subjccts. C1in Chern 197-4: 20: 1520-7.

167. Winkel P. Slallllnd BE. Bokelund H. The effecls of time of\'enipuncturc on varialin of serum constiluenlS. Am J ClinPathol 1975: 64: 433.

168. Young OS. Harris EK. COIlo\·e E. Biological and Analy­tic Componcnls of Varialion in Long-Ternl Studies of SerumConstiluenls in Normal Subjects. C1in Chem 1971: 17: 403­10.

169. YOregir GT. Aksoy K. Arpaci A. OnlOkul1 l. Tuli A. Studieson red ccll glucose-6-phosphatc clehyclrogenase:evaluationIlf refercncc valucs. Ann Clin Biochelll 1994: 31: 50-5.

Nota de los autores: L.1 referencia 113 ha sido diminada.