Analytical Interferences and Physiological Limitations of Blood ...
Analytical Interferences and Physiological Limitations of Blood ...
Analytical Interferences and Physiological Limitations of Blood ...
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<strong>Analytical</strong> <strong>Interferences</strong> <strong>and</strong><strong>Physiological</strong> <strong>Limitations</strong> <strong>of</strong><strong>Blood</strong> Glucose MetersKen Ervin
Published informationPackage insertsReview articles (partial list)Boren <strong>and</strong> ClarkeTonyushkina <strong>and</strong> NicholsPitkin <strong>and</strong> RiceMontagnana et alWahlDunganArabadjief <strong>and</strong> NicholsHeller <strong>and</strong> FeldmanSpecific articles (partial list) Kimberly, et alFiore <strong>and</strong> DelangheLyon, et alKazmierczak <strong>and</strong> CatrouGoudable, et alZheng, et alVesper, et alKatelijne <strong>and</strong> DelangheTang, et al03162010 Ken Ervin Consulting Services
Package inserts address “Procedurallimitations” Sample relatede.g. Hct, pO 2 , DKA, HHNK, etc. Endogenous compounds Exogenous compounds EnvironmentalTemperatureHumidityAltitude03162010 Ken Ervin Consulting Services
The limitations <strong>of</strong> a product aredependent upon the choice <strong>of</strong>technology to achieve the design goals.03162010 Ken Ervin Consulting Services
BGM Design GoalsDrive the specifications <strong>and</strong> choice <strong>of</strong>technologyAccurate <strong>and</strong> preciseHighly specific*Stable at room temperature*Rapid test (use wholeblood directly)*Very easy to useSmall blood volume*Inexpensive meter*Cal code strategyLow cost/testMore recently No pO2 dependenceNo maltose interferenceNo hematocrit effect03162010 Ken Ervin Consulting Services
To meet the specifications,technologies are chosen for themeasurement device <strong>and</strong> its method <strong>of</strong>production03162010 Ken Ervin Consulting Services
BGM measurement based oncombining technologies Method <strong>of</strong> introducing sample to deviceMost devices now rely on capillary action, sometimes in twodirections Method to identify glucose in sample (specificity)Enzymatic reaction (GO, GDH, Hexokinase/G6PDH) Method to quantify glucoseColorimetricElectrochemical Method <strong>of</strong> calibration Methods to assess performance <strong>of</strong> the test orcorrect results03162010 Ken Ervin Consulting Services
<strong>Interferences</strong> <strong>and</strong> physiologicallimitations are related to choices <strong>of</strong>sample type <strong>and</strong> technology03162010 Ken Ervin Consulting Services
<strong>Interferences</strong> result from Analyte specificity issues or Sample <strong>and</strong> environmental influences on themeasurement reaction03162010 Ken Ervin Consulting Services
Analyte specificity Use <strong>of</strong> enzymes specific for glucoseGOGDHHexokinase/G6PDH03162010 Ken Ervin Consulting Services
Sample influences on measurement Endogenous substancesUric acidBilirubinLipemia, Hemolysis Exogenous substancesAcetominophenAscorbateMaltose, Icodextrin metabolitesMannitolDopamine03162010 Ken Ervin Consulting Services
Sample influences DKA, HHNKpH <strong>and</strong>/or ViscosityHyperosmolar, flow effectsLess water volume to reconstitute reagent03162010 Ken Ervin Consulting Services
Environmental influences <strong>Analytical</strong> VariabilityTemperatureHumidityAltitude (i.e. oxygen availability)03162010 Ken Ervin Consulting Services
<strong>Physiological</strong> limitations Sample choice Capillary, venous, or arterialActual concentrations are different <strong>and</strong> relationship may varyIf capillary; hypotension, perfusion <strong>and</strong> other conditions suchas Reynaud’s syndrome disturb normal relationshipAlternate site time lagpO 2 differences Hematocrit Smaller sample sizes increase the potential forresidue to influence results03162010 Ken Ervin Consulting Services
Some relevant examples How a pO 2 dependence became a maltoseinterference Hematocrit effects03162010 Ken Ervin Consulting Services
The pO 2 effectGOglucose + O 2 + H 2 O gluconic acid + H 2 O 2HRPOH 2 O 2 + dye precursor dye color + H 2 0(YSI <strong>and</strong> BeckmanGlucose Analyzer)(colorimetric)glucose + med (ox)GOgluconolactone + med (red)(electrochemical)med (red)E pote - + med (ox)03162010 Ken Ervin Consulting Services
How a pO2 interference became amaltose interference Original methods based on glucose oxidase coupledto a colorimetric indicator system.Oxygen available from atmosphere blood removed by blotting, wiping etc. exposed to air during the reaction time Electrochemical methods used mediatorsSystems calibrated for capillary blood Oxygen would interfere competitivelyUse <strong>of</strong> venous or arterial blood exacerbated this competition Venous reads higher; less 0 2 competition Arterial reads lower; more 0 2 competitionpO2 effects generally greater at lower glucose concentrations03162010 Ken Ervin Consulting Services
How a pO2 interference became amaltose interference Second Generation productsGO Open to atmospheric oxygen Oxygen blocked by windows or capillary designHexokinase/G6PDH03162010 Ken Ervin Consulting Services
How a pO2 interference became amaltose interference GDH-PQQ systems introduced to alleviate pO 2GDH reaction does not involve oxygenRT stable enzyme However, GDH-PQQ less specific for glucoseRecognizes maltose, galactose, xylose <strong>and</strong> other sugarswith glucose moiety, with false elevation <strong>of</strong> glucose results. Recent versions <strong>of</strong> GDH with NAD or FAD c<strong>of</strong>actorare more specific <strong>and</strong> stable.03162010 Ken Ervin Consulting Services
Hematocrit effects For a rapid test, WB is preferable if not necessary Most systems now report “plasma equivalent” Systems are calibrated at normal hematocrit. WB sample hematocrits may vary significantly(~15 to >70) Glucose content <strong>of</strong> whole blood as compared toplasma is inversely related with hematocrit.03162010 Ken Ervin Consulting Services
Hematocrit dependenceLittle method effectGreater method effect03162010 Ken Ervin Consulting Services
Hematocrit effects Hematocrit may influence access <strong>of</strong> plasma ordiffusion <strong>of</strong> glucose to measurement systemsuppressing results. Hematocrit effects generally greater at higherglucose concentrations Hematocrit can be measured <strong>and</strong> corrected forGreater imprecision?03162010 Ken Ervin Consulting Services
In Conclusion <strong>Limitations</strong> <strong>and</strong> interferences are related to theparticular technologies chosen. The unique goals <strong>of</strong> a BGM system make it unlikelythey will ever completely match a lab based system. The evolution <strong>of</strong> BGM devices is a demonstration <strong>of</strong>achieving a balance between a high degree <strong>of</strong>performance with a rapid, more versatile, easy touse system. Using a WB sample <strong>and</strong> reporting plasma (unlesscorrected for) introduces a ± 6% error in the range25-65 hct.03162010 Ken Ervin Consulting Services
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