, Melissa Yssel, MB ChB, FC Path(SA) Chem 139, and Wendy M. Zakowicz, BS 79 Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.

Background: This case conference reviews laboratory methods for assessing oxygenation status: arterial blood gases, pulse oximetry, and CO-oximetry. Caveats of these measurements are discussed in the context of two methemoglobinemia cases. Cases: Case 1 is a woman who presented with increased shortness of breath, productive cough, chest pain, nausea, fever, and cyanosis. CO-oximetry indicated a carboxyhemoglobin (COHb) fraction of 24.9%. She was unresponsive to O 2 therapy, and no source of carbon monoxide could be noted. Case 2 is a man who presented with syncope, chest tightness, and signs of cyanosis. His arterial blood was dark brown, and COoximetry showed a methemoglobin (MetHb) fraction of 23%. Issues: Oxygen saturation (SO 2 ) can be measured by three approaches that are often used interchangeably, although the measured systems are quite different. Pulse oximetry is a noninvasive, spectrophotometric method to determine arterial oxygen saturation (S a O 2 ). CO-oximetry is a more complex and reliable method that measures the concentration of hemoglobin derivatives in the blood from which various quantities such as hemoglobin derivative fractions, total hemoglobin, and saturation are calculated. Blood gas instruments calculate the estimated O 2 saturation from empirical equations using pH and PO 2 values. In most patients, the results from these methods will be virtually identical, but in cases of increased dyshemoglobin fractions, including methemoglobinemia, it is crucial that the distinctions and limitations of these methods be understood. Conclusions: SO 2 calculated from pH and PO 2 should be interpreted with caution as the algorithms used assume normal O 2 affinity, normal 2,3-diphosphoglycerate con-

The PFA-100 is a more efficient test; it can replace the bleeding time test as a component of the laboratory evaluation of children with a potential bleeding problem.

The osmole gap correlates better with mannitol serum concentrations than osmolality, and although it cannot predict a specific mannitol serum concentration, a normal osmole gap concentration, as we find at trough times, indicates sufficient clearance for a new mannitol dose.

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