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J Autom Methods Manag Chem 2010:1-7 Medizin Medizin The present work examines how human coagulation is influenced by gentamicin (gentamicin×H2SO4), an often used aminoglycoside antibiotic in clinical practice. As a potent broad-spectrum antibiotic, gentamicin is frequently used in life-threatening, septic conditions, in which physiologic human coagulation is already affected in terms of an increased tendency to a pathologic disseminated intravascular coagulation. The influence of gentamicin on the generation of thrombin, the most important enzyme of human coagulation, was analysed. 50 μl samples of N=139 unfrozen individual normal platelet poor citrated plasmas and of N=11 unfrozen normal citrated plasma pools were supplemented with the clinically relevant concentration of 0 to 19.6 mg/l of gentamicin on microtiter plates. Instantly afterwards, the RECA (recalcified coagulation activity assay) was performed. The important approximate 200% stimulatory concentrations (approx. SC200) of gentamicin on thrombin generation were determined in the clinically relevant ascending part of the coagulation reaction time vs. thrombin generation curve. 5 normal plasmas supplemented with gentamicin as well as with 0 IU/ml or 0.5 IU/ml of the low molecular weight heparin enoxaparinnatrium were also analysed. 130 of 139 (94%) of the individual normal plasmas triggered thrombin generation with an approx. SC200 of 2.0 ± 2.5 mg/l (MV ± 1SD). Of the N=139 individual normal plasmas that were supplemented with up to 20 mg/l of gentamicin, 6 of 139 (4%) were resistant towards gentamicin-triggered thrombin generation. 3 of 139 (2 %) plasmas did not have an approx. 200% stimulatory concentration, but had an approx. 50% inhibitory concentration of 1-2.5 mg/l of gentamicin. Gentamicin×H2SO4 triggers intrinsic coagulation and thus thrombin generation with great inter-individual differences. A hemostatic monitoring and testing of the individual sensibility to gentamicin is reasonable, especially in a critical pro-coagulant situation like sepsis. Thrombin opus:5495 Gentamicin application/pdf Thrombin In der vorliegenden Arbeit wurde untersucht, wie die Blutgerinnung durch das in der Klinik oft verwendete Aminoglykosid-Antibiotikum Gentamicin (Gentamicin×H2SO4) beeinflusst wird. Die Grundüberlegung ist, dass Gentamicin als potentes Breitspektrum-Antibiotikum oft in lebensbedrohlichen, septischen Zuständen eingesetzt wird, in denen die physiologische Blutgerinnung bereits beeinträchtigt ist, im Sinne einer pathologischen, disseminierten, intravasalen Koagulopathie. Hier wurde untersucht, wie Gentamicin sich auf die Generierung des wichtigsten Enzyms der Hämostase, Thrombin, auswirkt. Dafür wurden 139 individuelle Citrat-Plasmaproben und 11 Citrat-Plasmapools gesunder Probanden verwendet. 50 μl Proben wurden mit Gentamicin in der klinisch relevanten Konzentration von 0-19.6 mg/l in Mikrotiterplatten supplementiert. Das Citrat-Plasma wurde unmittelbar danach rekalzifiert und das in der Gerinnungsreaktions-Zeit (coagulation reaction time = CRT) entstandene Thrombin im ultra-sensitiven, ultra spezifischen RECA (recalcified coagulation activity assay) quantifiziert. Diejenige plasmatische Gentamicin- Konzentration, welche die intrinsische Thrombin-Generierung ca. zweifach stimuliert, also die klinisch-relevante approx. SC200 (approximate 200% stimulatory concentration), wurde in der Gentamicin-Konzentration vs. Thrombin-Generierungs- Graphik ermittelt. 5 normale Plasmen wurden auch nach Zugabe von 0.5 IU/ml niedermolekularem Heparin untersucht. Bei der Auswertung zeigten 130 von 139 individuellen normalen Plasmaproben (94%) eine durch Gentamicin zweifach verstärkte Thrombingenerierung im Konzentrationsbereich von 2.0 ± 2.5 mg/l (MV ± 1 SD). 6 von 139 individuellen Plasmaproben (4%) zeigten sich gegenüber einer durch Gentamicin ausgelösten Thrombingenerierung resistent. Bei 3 von 139 individuellen Plasmaproben (2%) zeigte Gentamicin einen inhibitorischen Effekt auf die Thrombingenerierung und zwar mit approximativ 50% inhibitorischen Konzentrationen (approx. IC50) von ca. 1-2 mg/l. Gentamicin aktiviert also die intrinsische Gerinnung mit großen inter-individuellen Unterschieden. Ein hämostaseologisches Monitoring und eine Testung der individuellen Empfindlichkeit der Gerinnung auf Gentamicin erscheinen unter einer Therapie mit Gentamicin, insbesondere in einer koagulatorisch kritischen Situation, wie einer septischen Erkrankung, sinnvoll. English 2014-04-10 doctoralThesis monograph ppn:338999396 2014-04-10 Philipps-Universität Marburg 2014 urn:nbn:de:hebis:04-z2014-03239 2014-04-07 https://archiv.ub.uni-marburg.de/diss/z2014/0323/cover.png Medical sciences Medicine Medizin Gentamicin