Thrombin Generation by Gentamicin

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 coa...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: Albert, Dada Aishe
Beteiligte: Stief, T. (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2014
Medizin
Ausgabe:http://dx.doi.org/10.17192/z2014.0323
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Zusammenfassung: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.
DOI:http://dx.doi.org/10.17192/z2014.0323