Volume 35, Issue 2

“Thrombocytopathia” describes inherited or acquired functional disorders of platelets. The complexity of functional and metabolic processes in platelets is associated with a multitude of possible pathologic disturbances, showing a high variability in the clinical picture. The diagnosis of thrombocytopathies by existing laboratory methods is limited by variable sensitivities and specificities for various pathophysiologic backgrounds. Furthermore, the clinical evaluation of laboratory results is complex because of high intra- and interindividual variability of the platelet function. In daily routine diagnostics, a detailed patient history and clinical examination combined with aggregometry-based laboratory methods remains the central approach to diagnose a platelet function disorder.

“Thrombocytopathia” describes inherited or acquired functional disorders of platelets. The complexity of functional and metabolic processes in platelets is associated with a multitude of possible pathologic disturbances, showing a high variability in the clinical picture. The diagnosis of thrombocytopathies by existing laboratory methods is limited by variable sensitivities and specificities for various pathophysiologic backgrounds. Furthermore, the clinical evaluation of laboratory results is complex because of high intra- and interindividual variability of the platelet function. In daily routine diagnostics, a detailed patient history and clinical examination combined with aggregometry-based laboratory methods remains the central approach to diagnose a platelet function disorder.

Assessment of urinary organic acids represents an established approach within selective screening for inborn errors of metabolism. Utilizing gas chromatography and mass spectrometry, this analysis can contribute to the diagnosis of dozens of diseases. For diagnostic evaluation of analytical data it is essential that the requesting physician provides basic clinical information. Considering the often available therapeutic options, it is of special importance to increase the awareness of organic acid disorders and to include them in the list of differential diagnoses especially in (pediatric-) neurological disease.

Assessment of urinary organic acids represents an established approach within selective screening for inborn errors of metabolism. Utilizing gas chromatography and mass spectrometry, this analysis can contribute to the diagnosis of dozens of diseases. For diagnostic evaluation of analytical data it is essential that the requesting physician provides basic clinical information. Considering the often available therapeutic options, it is of special importance to increase the awareness of organic acid disorders and to include them in the list of differential diagnoses especially in (pediatric-) neurological disease.

In addition to the monographs which have been published in the last 6 years by the working group “Drug Monitoring” of the Swiss Society of Clinical Chemistry (SSCC) [Rentsch, Fathi, Grignaschi, Magnin, Printzen, Thormann, J Lab Med 29: 287–97, 2005 – Rentsch, Buhl, Eap, Fathi, Jöchle, Magnin, J Lab Med 34: 129–39, 2010], new monographs have been written. The data presented in these monographs provide an overview of the information which is important for the request and interpretation of the results. Therefore, laboratory health professionals and the receivers of the reports are the targeted readers. With the exception of digoxin, the drugs presented in this series are not administered frequently and are only analyzed in special situations. First, information about pharmacology and pharmacokinetics of these drugs (protein binding, metabolic pathways and enzymes involved, elimination half-life time and elimination route(s) of the parent drug and therapeutic as well as toxic concentrations) is given. Secondly, the indications for therapeutic drug monitoring are listed. Last but not least, important preanalytical information is provided, including time points of blood sampling and time interval after which steady-state concentrations are reached after changing the dose. Furthermore, the stability of the drug and its metabolite(s) after blood sampling are described. For readers with a specific interest, references to important publications are given. The number of the monographs will be further enlarged. The updated files are presented on the homepage of the SSCC (www.sscc.ch). We hope that these monographs are helpful for the better handling of therapeutic drug monitoring and we are looking forward to receiving comments from the readers.   Zusammenfassung Ergänzend zu den in den letzten sechs Jahren publizierten Arzneimittelmonographien der Arbeitsgruppe Medikamente der Schweizerischen Gesellschaft für Klinische Chemie (SGKC) [Rentsch, Fathi, Grignaschi, Magnin, Printzen, Thormann, J Lab Med 29: 287–97, 2005 – Rentsch, Buhl, Eap, Fathi, Jöchle, Magnin, J Lab Med 34: 129–39, 2010], sind weitere Monographien erstellt worden. Wiederum sollen diese Monographien dem Labormediziner bzw. dem Empfänger der Befunde eine Übersicht über die wichtigsten Informationen geben, die für die Veranlassung einer Analyse bzw. für die Interpretation der Resultate hilfreich sind. In dieser Serie werden verschiedene Medikamente vorgestellt, die mit Ausnahme von Digoxin nur noch selten verordnet oder deren Konzentration nur in speziellen Fällen im Blut bestimmt werden. Die einzelnen Monographien beinhalten einerseits Angaben zu klinisch-pharmakologischen Daten wie zum Beispiel zu den Proteinbindungen, Metabolisierungswegen und daran beteiligten Enzymen, Halbwertszeiten und Eliminationswege der Muttersubstanz, sowie Informationen zu therapeutischen bzw. toxischen Bereichen. Andererseits werden bei jeder Substanz die Indikationen für das Therapeutic Drug Monitoring aufgelistet und wichtige Angaben zur Präanalytik gemacht (Zeitpunkt der Blutentnahme und Zeitpunkt des Erreichens einer steady-state-Situation nach einer Dosisänderung). Ausserdem werden Angaben über die Stabilität der Medikamente bzw. ihrer Metaboliten nach der Blutentnahme gemacht. Für die interessierten Leser sind die verwendeten Referenzen als Zitate aufgeführt. Die Zahl der Monographien wird weiterhin ergänzt. Die aktuellsten Versionen der Monographien sind auf der Homepage der SGKC abrufbar (www.sscc.ch). Wir hoffen, dass diese Monographien im Umgang mit dem Therapeutic Drug Monitoring hilfreich sein werden und freuen uns über Kommentare und Bemerkungen.

Innovative technologies play an important role within the health care sector. They not only improve the quality of treatment and enable life prolonging and life-supporting measures. Within an increasing efficiency and quality orientated competitive environment, they also support the provision of health services by medical service providers, for instance hospitals, and allow them to position themselves within the market and safeguard their competitive edge. Alongside the general financial viability is the actual adaption and acceptance of the innovation by the medical personnel essential for the success of a newly introduced medical device. Innovative technologies often impact the existing processes, making them obsolete which increases the necessity for revision and reorganisation. A redesign of the processes concerned is generally only feasible through an active integration of all parties concerned. Change management can be seen as an essential requirement to coordinate the introduction of innovations as well as the redesign of processes within hospital wards to increase the clinical and economical success and to decrease possible failings, especially during the introduction phase of the innovation. Within a study project, the Center for Hospital-Management conducted and analysed the introduction and utilisation of interconnected point-of-care meters in hospitals in Austria, Germany and Switzerland. Beside constrains also factors for success which advocate a fast introduction and adaption of the interconnected point-of-care meters could be identified.

Innovative technologies play an important role within the health care sector. They not only improve the quality of treatment and enable life prolonging and life-supporting measures. Within an increasing efficiency and quality orientated competitive environment, they also support the provision of health services by medical service providers, for instance hospitals, and allow them to position themselves within the market and safeguard their competitive edge. Alongside the general financial viability is the actual adaption and acceptance of the innovation by the medical personnel essential for the success of a newly introduced medical device. Innovative technologies often impact the existing processes, making them obsolete which increases the necessity for revision and reorganisation. A redesign of the processes concerned is generally only feasible through an active integration of all parties concerned. Change management can be seen as an essential requirement to coordinate the introduction of innovations as well as the redesign of processes within hospital wards to increase the clinical and economical success and to decrease possible failings, especially during the introduction phase of the innovation. Within a study project, the Center for Hospital-Management conducted and analysed the introduction and utilisation of interconnected point-of-care meters in hospitals in Austria, Germany and Switzerland. Beside constrains also factors for success which advocate a fast introduction and adaption of the interconnected point-of-care meters could be identified.

Background: Bacterial meningitis in adults is a rapid progressive and life threatening condition. Monitoring of cytokines such as interleukin (IL) 6 by automated chemiluminescence poses an attractive alternative to monitoring of conventional biomarkers. Methods: In a prospective setting, we studied 523 consecutive neurological patients within a 6 month period. 419 complete datasets could be included the analysis. Results: In control patients (with neurological disease excluded), the 95. percentile of cerebrospinal fluid (CSF) IL-6 was 7.0 pg/mL and the ratio of CSF IL-6 /serum IL-6 was <2.67. In our population, acute inflammation of the central nervous system was observed in 5.7% of the patients only. In all patients with bacterial meningitis, very high concentrations of CSF IL-6 were observed. In viral meningitis, the concentration of CSF IL-6 was heterogeneous. In acute meningitis, the performance of CSF IL-6 was similar to the performance of CSF lactate. Very high CSF IL-6 concentrations in otherwise normal CSF were observed in few patients with seizures. Conclusions: In adults, CSF IL-6 cannot differentiate between bacterial and viral meningitis. Low concentrations of CSF IL6 do not exclude viral meningitis but might be a helpful biomarker to exclude acute bacterial inflammation of the central nervous system. However, given the very low incidence of bacterial meningitis in our adult neurological population, our study does not indicate a better targeted use of antibiotic therapy when IL-6 is added to the routine CSF analysis panel.   Zusammenfassung Hintergrund: Die bakterielle Meningitis in Erwachsenen ist eine rapid progrediente, lebensbedrohliche Erkrankung. Die Messung von Cytokinen wie Interleukin (IL) 6 mittels automatisierter Chemilumineszenz scheint eine attraktive Alternative zur Messung der konventionellen Biomarkern zu sein. Methode: In dieser prospektiven Studie wurden 523 neurologische Patienten innerhalb eines halben Jahres untersucht. 419 komplette Datensätze standen für die Analyse zur Verfügung. Ergebnisse: In den Kontrollpatienten (mit ausgeschlossener neurologischer Erkrankung) lag die 95. Perzentile des Liquor-IL-6 bei 7,0 pg/mL und das Verhältnis von Liquor-IL-6/Serum IL-6 war <2,67. In unsere Studienpopulation wurde eine akute Entzündung des zentralen Nervensystems allerdings nur in 5,7% der Patienten gefunden. In allen Patienten mit bakterieller Meningitis fanden sich sehr hohe Konzentrationen von Liquor-IL-6. In Patienten mit viraler Meningitis reichten die Konzentrationen von Liquor-IL-6 von niedrig bis sehr hoch. In akuter Meningitis verhielt sich die Aussagekraft von Liquor-IL-6 ähnlich wie die von Liquorlaktat. Isoliert stark erhöhtes Liquor IL-6 fand sich bei einigen Patienten mit Krampfanfällen. Schlussfolgerung: Bei Erwachsenen ist Liquor-IL-6 nicht geeignet zur Differenzierung zwischen bakterieller und viraler Meningitis. Niedrige Konzentrationen von Liquor-IL6 schließen eine virale Meningitis nicht aus. Die Messung könnte aber hilfreich zum Ausschluss einer akuten bakteriellen Entzündung des zentralen Nervensystems sein. Wegen der äußerst geringen Inzidenz einer bakteriellen Meningitis in unseren erwachsenen neurologischen Patienten folgern wir aus dieser Studie, dass die Aufnahme von Liquor-IL-6 in die Routineliquoruntersuchung nicht zu einem gezielteren Einsatz der Antibiotikatherapie führen würde.