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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...
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| Format: | Doctoral Thesis |
| Language: | English |
| Published: |
Philipps-Universität Marburg
2014
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| Online Access: | PDF Full Text |
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| Summary: | 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. |
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| DOI: | 10.17192/z2014.0323 |