Erratum : Sawtooth potassium and hemoglobin results (Clinical Chemistry (2019) 65 (1463–1464) DOI: 10.1373/clinchem.2019.304394)

CASE DESCRIPTION A 5-year-old boy was admitted with dyspnea, fever, night sweats, and unexplained bruising. Radiography revealed several pulmonary consolidations, and laboratory investigations showed marked hyperleukocytosis with 90% blasts. He was diagnosed with T-cell acute lymphoblastic leukemia. Hemoglobin (Hb)2 and potassium results in the subsequent days, during therapy, showed a sawtooth pattern [Fig. 1: central lab, solid dots; point of care (POC), open dots]. The physician was confused and unsure what Hb and potassium results to act on and contacted the laboratory. (Figure Presented)

Erratum : Sawtooth potassium and hemoglobin results (Clinical Chemistry (2019) 65 (1463–1464) DOI: 10.1373/clinchem.2019.304394)

CASE DESCRIPTION A 5-year-old boy was admitted with dyspnea, fever, night sweats, and unexplained bruising. Radiography revealed several pulmonary consolidations, and laboratory investigations showed marked hyperleukocytosis with 90% blasts. He was diagnosed with T-cell acute lymphoblastic leukemia. Hemoglobin (Hb)2 and potassium results in the subsequent days, during therapy, showed a sawtooth pattern [Fig. 1: central lab, solid dots; point of care (POC), open dots]. The physician was confused and unsure what Hb and potassium results to act on and contacted the laboratory. (Figure Presented)

Quantification of coagulation factor VIII in human plasma with liquid chromatography tandem mass spectrometry using a selective sample purification with camelid nanobodies

Patients with hemophilia A are currently diagnosed and monitored by measuring the activity of coagulation factor VIII (FVIII) in plasma mostly with the one-stage clotting assay (OSA). Although the OSA is routinely available in many clinical laboratories, it has in some circumstances relatively low sensitivity and specificity. Therefore, the FVIII activity as a biomarker does not always correlate with the bleeding phenotype. Therefore, we have developed a liquid chromatography tandem mass spectrometry method to quantify the concentration of coagulation FVIII in plasma which would allow us to investigate the relation between FVIII plasma concentration, FVIII activity and bleeding tendency in future studies. LC-MS/MS method was set up by firstly dissociation Von Willebrand factor (VWF) from coagulation factor VIII by triggering the coagulation cascade to occur thus generating active factor VIII (FVIIIa). FVIIIa was then selectively extracted by means of immunoaffinity interaction using anti-FVIII camelid nanobody, after which FVIIIa was eluted, heat denatured and trypsin digested. Finally, a FVIII specific peptide was used as a surrogate for quantification by mass spectrometry. Critical method parameters such as antibody amount, incubation time, sample volume and type of streptavidin 96 well plate were optimized. The method was validated according to European Medicines Agency (EMA) guidelines where an LLOQ of 1 ng/mL was obtained using 50 μL of citrate plasma sample. Within-run and between-run accuracy and precision for quality control (QC) samples, LLOQ (1 ng/mL), QC Low (5 ng/mL), QC Med (150 ng/mL), QC High (300 ng/mL) were within the threshold of 15% relative standard deviation (RSD) and Bias. The selective immunoaffinity method which was used in combination with a highly sensitive mass spectrometer allowed for an unpresented LLOQ of 1 ng/mL utilizing 50 μL plasma sample. This method will be used to investigate the beneficial value of FVIII plasma concentration which may be used in conjunction with FVIII activity for patient diagnosis and dosage optimization

Impact of interactions between drugs and laboratory test results on diagnostic test interpretation - a systematic review

Intake of drugs may influence the interpretation of laboratory test results. Knowledge and correct interpretation of possible drug-laboratory test interactions (DLTIs) is important for physicians, pharmacists and laboratory specialists. Laboratory results may be affected by analytical or physiological effects of medication. Failure to take into account the possible unintended influence of drug use on a laboratory test result may lead to incorrect diagnosis, incorrect treatment and unnecessary follow-up. The aim of this review is to give an overview of the literature investigating the clinical impact and use of DLTI decision support systems on laboratory test interpretation. Particular interactions were reported in a large number of articles, but they were fragmentarily described and some papers even reported contradictory findings. To provide an overview of information that clinicians and laboratory staff need to interpret test results, DLTI databases have been made by several groups. In a literature search, only four relevant studies have been found on DLTI decision support applications for laboratory test interpretation in clinical practice. These studies show a potential benefit of automated DLTI messages to physicians for the correct interpretation of laboratory test results. Physicians reported 30-100% usefulness of DLTI messages. In one study 74% of physicians sometimes even refrained from further additional examination. The benefit of decision support increases when a refined set of clinical rules is determined in cooperation with health care professionals. The prevalence of DLTIs is high in a broad range of combinations of laboratory tests and drugs and these frequently remain unrecognized

Diagnostic error as a result of drug-laboratory test interactions

Background Knowledge of possible drug-laboratory test interactions (DLTIs) is important for the interpretation of laboratory test results. Test results may be affected by physiological or analytical drug effects. Failure to recognize these interactions may lead to misinterpretation of test results, a delayed or erroneous diagnosis or unnecessary extra tests or therapy, which may harm patients. Content Thousands of interactions have been reported in the literature, but are often fragmentarily described and some papers even reported contradictory findings. How can healthcare professionals become aware of all these possible interactions in their individual patients? DLTI decision support applications could be a good solution. In a literature search, only four relevant studies have been found on DLTI decision support applications in clinical practice. These studies show a potential benefit of automated DLTI messages to physicians for the interpretation of laboratory test results. All physicians reported that part of the DLTI messages were useful. In one study, 74% of physicians even sometimes refrained from further additional examination. Summary and outlook Unrecognized DLTIs potentially cause diagnostic errors in a large number of patients. Therefore, efforts to avoid these errors, for example with a DLTI decision support application, could tremendously improve patient outcome