8 research outputs found
Performance of laboratory tests used to measure blood phenylalanine for the monitoring of patients with phenylketonuria
Analysis of blood phenylalanine is central to the monitoring of patients with phenylketonuria (PKU) and ageârelated phenylalanine target treatmentâranges (0â12âyears; 120â360âÎźmol/L, andâ>12âyears; 120â600âÎźmol/L) are recommended in order to prevent adverse neurological outcomes. These target treatmentâranges are based upon plasma phenylalanine concentrations. However, patients are routinely monitored using dried bloodspot (DBS) specimens due to the convenience of collection. Significant differences exist between phenylalanine concentrations in plasma and DBS, with phenylalanine concentrations in DBS specimens analyzed by flowâinjection analysis tandem mass spectrometry reported to be 18% to 28% lower than paired plasma concentrations analyzed using ionâexchange chromatography. DBS specimens with phenylalanine concentrations of 360 and 600âÎźmol/L, at the critical upperâtarget treatmentârange thresholds would be plasma equivalents of 461 and 768âÎźmol/L, respectively, when a reported difference of 28% is taken into account. Furthermore, analytical test imprecision and bias in conjunction with preâanalytical factors such as volume and quality of blood applied to filter paper collection devices to produce DBS specimens affect the final test results. Reporting of inaccurate patient results when comparing DBS results to target treatmentâranges based on plasma concentrations, together with interâlaboratory imprecision could have a significant impact on patient management resulting in inappropriate dietary change and potentially adverse patient outcomes. This review is intended to provide perspective on the issues related to the measurement of phenylalanine in blood specimens and to provide direction for the future needs of PKU patients to ensure reliable monitoring of metabolic control using the target treatmentâranges
Investigation of the relationship between phenylalanine in venous plasma and capillary blood using volumetric blood collection devices
Measurement of plasma and dried blood spot (DBS) phenylalanine (Phe) is key to monitoring patients with phenylketonuria (PKU). The relationship between plasma and capillary DBS Phe concentrations has been investigated previously, however, differences in methodology, calibration approach and assumptions about the volume of blood in a DBS subâpunch has complicated this. Volumetric blood collection devices (VBCDs) provide an opportunity to reâevaluate this relationship. Paired venous and capillary samples were collected from patients with PKU (n = 51). Capillary blood was collected onto both conventional newborn screening (NBS) cards and VBCDs. Specimens were analysed by liquidâchromatography tandem massâspectrometry (LCâMS/MS) using a common calibrator. Use of VBCDs was evaluated qualitatively by patients. Mean bias between plasma and volumetrically collected capillary DBS Phe was â13%. Mean recovery (SD) of Phe from DBS was 89.4% (4.6). VBCDs confirmed that the volume of blood typically assumed to be present in a 3.2 mm subâpunch is overâestimated by 9.7%. Determination of the relationship between plasma and capillary DBS Phe, using a single analytical method, common calibration and VBCDs, demonstrated that once the underârecovery of Phe from DBS has been taken into account, there is no significant difference in the concentration of Phe in plasma and capillary blood. Conversely, comparison of plasma Phe with capillary DBS Phe collected on a NBS card highlighted the limitations of this approach. Introducing VBCDs for the routine monitoring of patients with PKU would provide a simple, acceptable specimen collection technique that ensures consistent sample quality and produces accurate and precise blood Phe results which are interchangeable with plasma Phe
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Investigation of the relationship between phenylalanine in venous plasma and capillary blood using volumetric blood collection devices
AbstractMeasurement of plasma and dried blood spot (DBS) phenylalanine (Phe) is key to monitoring patients with phenylketonuria (PKU). The relationship between plasma and capillary DBS Phe concentrations has been investigated previously, however, differences in methodology, calibration approach and assumptions about the volume of blood in a DBS subâpunch has complicated this. Volumetric blood collection devices (VBCDs) provide an opportunity to reâevaluate this relationship. Paired venous and capillary samples were collected from patients with PKU (nâ=â51). Capillary blood was collected onto both conventional newborn screening (NBS) cards and VBCDs. Specimens were analysed by liquidâchromatography tandem massâspectrometry (LCâMS/MS) using a common calibrator. Use of VBCDs was evaluated qualitatively by patients. Mean bias between plasma and volumetrically collected capillary DBS Phe was â13%. Mean recovery (SD) of Phe from DBS was 89.4% (4.6). VBCDs confirmed that the volume of blood typically assumed to be present in a 3.2âmm subâpunch is overâestimated by 9.7%. Determination of the relationship between plasma and capillary DBS Phe, using a single analytical method, common calibration and VBCDs, demonstrated that once the underârecovery of Phe from DBS has been taken into account, there is no significant difference in the concentration of Phe in plasma and capillary blood. Conversely, comparison of plasma Phe with capillary DBS Phe collected on a NBS card highlighted the limitations of this approach. Introducing VBCDs for the routine monitoring of patients with PKU would provide a simple, acceptable specimen collection technique that ensures consistent sample quality and produces accurate and precise blood Phe results which are interchangeable with plasma Phe.</jats:p