Cross-sectional audit assessing the quality of dried bloodspot specimens received by UK metabolic biochemistry laboratories for the biochemical monitoring of individuals with Phenylketonuria

Abstract

Background Sapropterin has been approved as a treatment option for individuals with Phenylketonuria in the United Kingdom. Individuals are assessed as responsive to Sapropterin by a ≥30% reduction in Phenylalanine (Phe) concentrations using dried blood spot (DBS) specimens. DBS quality is critical for accurate and precise measurement of Phe. Currently, UK national guidelines for DBS specimen acceptance do not exist for patient-collected DBS specimens. We adopted evidence-based guidelines for specimen acceptance criteria and retrospectively assessed the impact of introducing these guidelines on specimen rejection rates. Methods: Laboratories were invited to audit the quality of DBS specimens routinely received for Phe monitoring using: (1) existing acceptance/rejection criteria and (2) proposed national guidelines. Results Ten laboratories audited 2111 specimens from 1094 individuals. Using existing local guidelines, the median rejection rate was 4.0% (IQR 1.5–7.2%). This increased to 21.9% (IQR 10.0–33.0%) using the proposed guidelines. Where reason(s) for rejection were provided ( n = 299); 211/299 (70.6%) of DBS specimens were too small or multi-spotted. 380 individuals had more than one sample evaluated; 231/380 (60.8%) provided specimens of acceptable quality, 37/380 (9.7%) consistently provided poor-quality DBS specimens. Conclusions There is significant variability in the quality of patient-collected DBS specimens. If unacceptable specimens are not rejected, imprecise/inaccurate results will be used in clinical decision making. Using annual workload data for England, this equates to 12,410 incorrect results. Individuals and parents/carers should receive ongoing training in blood collection technique to ensure use of evidence-based acceptability criteria does not cause undue distress from increased sample rejection rates.

Newborn Screening for High-Risk Congenital Heart Disease by Dried Blood Spot Biomarker Analysis

“…We visually inspected DBS but did not formally test for possible variations in blood volumes, which may have influenced our results; just as different DBS sampling methods might in other settings. 57 , 58 Subgroup analyses of specific CHD types was limited to cases with coarctation of the aorta due to small numbers of other types of congenital heart disease included in this study, such as single ventricle lesions. We attempted to minimize selection bias by approaching eligible cases according to date of birth, starting with participants born most recently.…”

“…In some cases, requested material was unavailable or insufficient. We visually inspected DBS but did not formally test for possible variations in blood volumes, which may have influenced our results; just as different DBS sampling methods might in other settings . Subgroup analyses of specific CHD types was limited to cases with coarctation of the aorta due to small numbers of other types of congenital heart disease included in this study, such as single ventricle lesions.…”

Investigation of the relationship between phenylalanine in venous plasma and capillary blood using volumetric blood collection devices

“…The historic practice where laboratories have employed a more lenient approach to ‘special’ specimens is no longer acceptable, yet many laboratories remain reluctant to reject DBS specimens, particularly from children, which leads to considerable variation in practice. A recent audit 27 demonstrated that introducing DBS quality acceptance criteria would increase specimen rejection rates in England from 4% to 22%. Extrapolating this to the annual Phe monitoring workload in England would correspond to the rejection of 12 410 specimens each year.…”

“…Capillary blood samples were dried at ambient temperature for 3 h then stored in foil bags with desiccant at −20°C. The quality of the DBS specimens was assessed against the proposed UK Metabolic Biochemistry Network guidelines for monitoring of inherited metabolic diseases 27 . All samples met the acceptance criteria.…”

“…proposed UK Metabolic Biochemistry Network guidelines for monitoring of inherited metabolic diseases. 27 All samples met the acceptance criteria. Images of the collection devices and DRT are shown in Figure 1A-C respectively.…”