[Newborn screening in France: news and perspectives]. / Le dépistage néonatal en France : actualités et perspectives.

Newborn screening is a major public health concern. In France, it was established in 1972 with systematic screening for phenylketonuria. Subsequently, other screenings, including congenital hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis, and sickle cell disease, were added. The introduction of tandem mass spectrometry in screening laboratories in 2020 enabled the inclusion of eight additional inherited metabolic diseases: aminoacidopathies (tyrosinemia type I, maple syrup urine disease, and homocystinuria), organic acidurias (isovaleric and glutaric type I acidurias), and disorders of fatty acid metabolism (MCADD, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), and primary carnitine deficiency). We briefly present these newly added diseases, of which public awareness is still incomplete.

[Uncertainty of measurement and result from a complex calculation: about the risk of fetal Down's syndrome by maternal serum markers]. / Incertitude de mesure et résultat issu d'un calcul complexe : le cas du risque de trisomie 21 fœtale par les marqueurs sériques maternels.

Screening for fetal Down's syndrome has the peculiarity of combining the biochemical assay of 2 or 3 serum markers with the risk associated with maternal age. If the accuracy of measurement of each parameter is known by the biologist, the uncertainty of the ultimate risk to the patient is not. Indeed, the means of risk calculation involve numerous multi-parameter equations which are not practical for daily use. Defining a re-test limit on thresholds of 1/50 and 1/1,000 is therefore impossible. Since the use of an arbitrarily defined threshold is not being satisfactory, we propose, by default, a methodology based on the exploitation of patient files in the laboratory with risks close to the two decision thresholds. Modulations of the concentrations of all the markers according to their uncertainty allow new risks to be obtained, which can be averaged and framed by an interval of several standard deviations. Choosing the level of uncertainty, the number of files to include, the number of standard deviations framing the average risk, as well as the calculation software, are all choices available to the biologist. The proposed methodology is therefore highly empirical but open, and adaptable, to the specific environment and performance capabilities of each and every laboratory involved.

Leukocytosis interference in clinical chemistry: Shall we still interpret test results without hematological data?

BACKGROUND: Extreme leukocytosis is known to induce remarkable variations of some clinical chemistry tests, thus leading to possible clinical misinterpretation. This study aimed to define whether also moderate leukocytosis may influence the stability of glucose and blood gases. METHODS: Blood samples are sent to the local laboratory through a pneumatic tube system. Clinical chemistry testing is routinely performed using Lithium-heparin tubes (for glucose) and heparin blood gases syringes (for blood gas analysis). Stability of glucose (in uncentrifuged blood tubes) and blood gases (in syringes) was hence evaluated in samples maintained at room temperature. Results were also analyzed in 2 subgroups of samples with different leukocyte counts, i.e., those with leukocytes <15 × 109/L and those with leukocytes >15 × 109/L. RESULTS: An accelerated decrease of pH was observed in blood gases syringes with leukocytosis (i.e., >15 × 109/L), while no difference was noted for other blood gases parameters (PCO2, PO2). Spurious and time-dependent hypoglycemia was noted in uncentrifuged blood tubes of patients with leukocytosis. CONCLUSIONS: The results of our study suggest that even modest leukocytosis (i.e., around 15 × 109/L), which is frequently encountered in clinical and laboratory practice, may be associated with significant variations of both glucose and pH. This would lead us to conclude that results of these parameters shall be accompanied by those of hematologic testing to prevent clinical misinterpretation, namely with leukocyte counts.

Pneumatic tube system transport and false hyperkalemia related to leukocytosis: a retrospective analysis.

Extreme leukocytosis may lead to false hyperkalemia when blood samples are conveyed by pneumatic tube system (PTS). The aim of this study was to define whether even moderate leukocytosis and also non malignancy cells like neutrophils may influence potassium values after PTS transportation. MATERIALS AND METHODS: Uncentrifuged blood samples are sent to the local laboratory through PTS. Data were retrospectively collected from routine testing carried out on all specimens arrived in the laboratory between September 2017 and March 2018. Clinical chemistry testing is routinely performed using lithium-heparin tubes. When false hyperkalemia induced by leukocytosis is suspected, potassium measurement is then performed in serum (clotting activator tubes) or whole blood samples. The analysis was focused on samples with both leukocytosis (i.e., >15×109/L) and plasma potassium >5.0 mmol/L, before any corrective therapeutic measure to lower potassium levels was established. RESULTS: A total number of 18 samples were included in our analysis, 9 drawn from patients with hematologic malignancies and 9 without. In the 9 patients without hematologic malignancies (median leukocyte count, 20.4×109/L), the median potassium value was 5.4 mmol/L in plasma and 4.5 mmol/L in serum or whole blood. In the 9 patients with hematologic malignancies (median leukocyte count, 151.9×109/L; p <0.001), the median potassium value was 7.7 mmol/L in plasma and 4.3 mmol/L in serum or whole blood (median difference, 2.9 mmol/L; p <0.001). CONCLUSION: The results of our study suggest that even modest leukocytosis (i.e., around 15x109/L), which can be frequently encountered in clinical practice, may be associated with a significant variation of plasma potassium. This would lead us to conclude that plasma samples transportation by PTS should be avoided in patients with even mild leukocytosis.

Benefit of point of care testing in patient with major hyperleukocytosis.

We report a case of a child with major leukocytosis (800 × 109/L) leading to a false increase in plasma potassium and an unexpected spurious decrease in sodium. To suppress interferences due to hyperleukocytosis, our laboratory protocol consists of collecting blood on Clotting Activator/Serum tubes (CAS) and/or carrying samples by human courier. CAS tube analysis showed a decreased level of hyperkalemia and sodium within the reference range (consistent with point of care measurements). Pseudo-hyperkalemia caused by extreme hyperleukocytosis has been well documented and is caused by lysis of leukocytes and cell contents release (including potassium) into the plasma, especially regarding blast cells, which are at even higher risk of lysis. Pseudo-hyponatremia mechanism has not yet been described. This interference could be multifactorial; blast lysis could cause intracellular ionic content release, therefore, modifying extracellular fluid ionic ratios. To correct this interference, the hypothesis is that collecting samples on CAS tubes or monitoring patient using point of care analysis are the most efficient solutions, as transport mode did not resolve interference issues. We speculate that cell lysis related to interference is multifactorial but mainly caused by centrifugation. To confirm this, we would have liked to compare ion levels before and after centrifugation.