AbstractsBiology & Animal Science

Thrombin Generation by Gentamicin

by Dada Aishe Albert




Institution: Philipps-Universität Marburg
Department: Medizin
Degree: PhD
Year: 2014
Record ID: 1099037
Full text PDF: http://archiv.ub.uni-marburg.de/diss/z2014/0323


Abstract

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. 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…