Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten

Die frühe Diagnose der Sepsis und der pathologischen disseminierten intravaskulären Gerinnung (PDIC) und damit auch die frühzeitige Einleitung der Therapie ist heute eine der zentralen Herausforderungen der Medizin. Die vorliegende laborchemische Arbeit beschäftigte sich mit der Erhebung von Hämosta...

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author Weiste, Bettina
spellingShingle Weiste, Bettina
Medizin, Gesundheit
Sepsis
Sepsis
Verbrauchskoagulopathie
Coagulation
Koagulation
Monozyt
Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten
Sepsis and septic shock almost invariably lead to hemostatic abnormalities. Clinical and experimental studies showed that it is the pathologic disseminated intravascular coagulation (PDIC) that causes microvascular dysfunction, which can result in organ failure. Rapid diagnosis of PDIC is a major challenge in clinical medicine. Many hemostasis parameters are available and the question arises, which of them, especially which of the new ones, can help to start a life rescuing treatment in time. The aim of this thesis was to study markers of cell destruction and hemostasis activation in order to improve the rapid laboratory diagnosis of early severe sepsis. The alterations of hemostasis in septic patients compared to normal plasma were analysed. Plasma of intensive care patients is very unstable. Therefore, in this study EDTA-plasma of intensive care patients or of healthy donors (control group) was stabilized for the first time by supramolar concentrations of arginine before freezing/thawing and analysis. Established markers of PDIC are the thrombocyte count, antithrombin III-activity, fibrinogen- and D-dimer-concentration. The present study showed that quantification in plasma of the in vivo generated circulating amidolytic thrombin activity, fibrinogenfunction/-antigen ratio, tissue factor, sL-selectin, and endotoxin reactivity add much more important information about the pathophysiology of severe sepsis and enable a rapid diagnosis of early sepsis.
ref_str_mv references
oai_set_str_mv ddc:610
doc-type:doctoralThesis
open_access
xMetaDissPlus
dewey-raw 610
dewey-search 610
genre Medical sciences, Medicine
genre_facet Medical sciences, Medicine
topic_facet Medizin, Gesundheit
topic Medizin, Gesundheit
Sepsis
Sepsis
Verbrauchskoagulopathie
Coagulation
Koagulation
Monozyt
format Dissertation
title Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten
title_short Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten
title_full Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten
title_fullStr Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten
title_full_unstemmed Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten
title_sort Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten
language German
title_alt Coagulation in severe sepsis with special focus on monocytes
publishDate 2010
era_facet 2010
url http://archiv.ub.uni-marburg.de/diss/z2010/0676/pdf/dbw.pdf
institution Medizin
building Medizin
last_indexed 2011-08-10T23:59:59Z
author2 Stief, Thomas (Dr.)
author2_role ths
description Die frühe Diagnose der Sepsis und der pathologischen disseminierten intravaskulären Gerinnung (PDIC) und damit auch die frühzeitige Einleitung der Therapie ist heute eine der zentralen Herausforderungen der Medizin. Die vorliegende laborchemische Arbeit beschäftigte sich mit der Erhebung von Hämostaseparametern bei Patienten mit schwerer Sepsis. Sowohl aktuell zur Diagnose der Sepsis und PDIC etablierte als auch neue Parameter wurden untersucht. Hämostaseparameter, welche eine klare Abgrenzung zur Norm ermöglichen, geben wertvolle Hinweise auf die Entwicklung von Sepsis und PDIC. Die Thrombozytenzahl, Antithrombin-III-Aktivität, Fibrinogen und die D-Dimer-Konzentration sind etablierte Parameter der PDIC. Als innovative Parameter zur Diagnose von PDIC bei Sepsis konnten insbesondere die zirkulierende amidolytische Thrombinaktivität und die Endotoxin-Reaktivität aufgezeigt werden. Die eventuelle Bedeutung von Monozytenfragmenten wurde im Rahmen dieser Arbeit ebenfalls untersucht. sCD14 war in den von uns durchgeführten Messungen kein guter Marker einer schweren Sepsis. Tissue factor und sL-Selectin hingegen fanden sich in stark erhöhten Mengen im Plasma der Sepsispatienten und könnten die Leukozytenzerstörung widerspiegeln. Verantwortlich für die Pathogenese der PDIC bei Sepsis könnte somit die toxische Wirkung von Endotoxinen auf Zellen, insbesondere auf Monozyten, sein. Die Zellfragmente triggern die Entstehung von Kallikrein und Thrombin. Zirkulierendes Thrombin generiert zirkulierendes Fibrin, welches sich am Endothel ablagert. Die fibrinolytische Kapazität ist bei Sepsis nicht ausreichend. Mikrothromben können wachsen, das Organ könnte ischämisch werden und ein Multiorganversagen resultieren.
publisher Philipps-Universität Marburg
first_indexed 2010-12-02T00:00:00Z
license_str http://archiv.ub.uni-marburg.de/adm/urhg.html
contents Sepsis and septic shock almost invariably lead to hemostatic abnormalities. Clinical and experimental studies showed that it is the pathologic disseminated intravascular coagulation (PDIC) that causes microvascular dysfunction, which can result in organ failure. Rapid diagnosis of PDIC is a major challenge in clinical medicine. Many hemostasis parameters are available and the question arises, which of them, especially which of the new ones, can help to start a life rescuing treatment in time. The aim of this thesis was to study markers of cell destruction and hemostasis activation in order to improve the rapid laboratory diagnosis of early severe sepsis. The alterations of hemostasis in septic patients compared to normal plasma were analysed. Plasma of intensive care patients is very unstable. Therefore, in this study EDTA-plasma of intensive care patients or of healthy donors (control group) was stabilized for the first time by supramolar concentrations of arginine before freezing/thawing and analysis. Established markers of PDIC are the thrombocyte count, antithrombin III-activity, fibrinogen- and D-dimer-concentration. The present study showed that quantification in plasma of the in vivo generated circulating amidolytic thrombin activity, fibrinogenfunction/-antigen ratio, tissue factor, sL-selectin, and endotoxin reactivity add much more important information about the pathophysiology of severe sepsis and enable a rapid diagnosis of early sepsis.
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J Clin Invest. 1994; 93:114-20. 1994 Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees 197 Visintin A, Mazzoni A, Spitzer JA, Segal DM. Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll- like receptor 4. Proc Natl Acad Sci U S A. 2001; 98:12156-61. 2001 Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Tolllike receptor 4 154 Schmaier AH, Rojkjaer R, Shariat-Madar Z. Activation of the plasma kallik- rein/kinin system on cells: a revised hypothesis. Thromb Haemost. 1999; 82:226-33. 1999 Activation of the plasma kallikrein/kinin system on cells: a revised hypothesis 157 Seidelin JB, Nielsen OH, Strom J. Soluble L-selectin levels predict survival in sepsis. Intensive Care Med. 2002; 28:1613-8. 2002 Soluble L-selectin levels predict survival in sepsis Blood, coagulation and fibrinolysis Gerinnung bei schwerer Sepsis unter besonderer Berücksichtigung der Monozyten Coagulation in severe sepsis with special focus on monocytes 2010 opus:3207 2011-08-10 Die frühe Diagnose der Sepsis und der pathologischen disseminierten intravaskulären Gerinnung (PDIC) und damit auch die frühzeitige Einleitung der Therapie ist heute eine der zentralen Herausforderungen der Medizin. Die vorliegende laborchemische Arbeit beschäftigte sich mit der Erhebung von Hämostaseparametern bei Patienten mit schwerer Sepsis. Sowohl aktuell zur Diagnose der Sepsis und PDIC etablierte als auch neue Parameter wurden untersucht. Hämostaseparameter, welche eine klare Abgrenzung zur Norm ermöglichen, geben wertvolle Hinweise auf die Entwicklung von Sepsis und PDIC. Die Thrombozytenzahl, Antithrombin-III-Aktivität, Fibrinogen und die D-Dimer-Konzentration sind etablierte Parameter der PDIC. Als innovative Parameter zur Diagnose von PDIC bei Sepsis konnten insbesondere die zirkulierende amidolytische Thrombinaktivität und die Endotoxin-Reaktivität aufgezeigt werden. Die eventuelle Bedeutung von Monozytenfragmenten wurde im Rahmen dieser Arbeit ebenfalls untersucht. sCD14 war in den von uns durchgeführten Messungen kein guter Marker einer schweren Sepsis. Tissue factor und sL-Selectin hingegen fanden sich in stark erhöhten Mengen im Plasma der Sepsispatienten und könnten die Leukozytenzerstörung widerspiegeln. Verantwortlich für die Pathogenese der PDIC bei Sepsis könnte somit die toxische Wirkung von Endotoxinen auf Zellen, insbesondere auf Monozyten, sein. Die Zellfragmente triggern die Entstehung von Kallikrein und Thrombin. Zirkulierendes Thrombin generiert zirkulierendes Fibrin, welches sich am Endothel ablagert. Die fibrinolytische Kapazität ist bei Sepsis nicht ausreichend. Mikrothromben können wachsen, das Organ könnte ischämisch werden und ein Multiorganversagen resultieren. 2010-12-02 Sepsis and septic shock almost invariably lead to hemostatic abnormalities. Clinical and experimental studies showed that it is the pathologic disseminated intravascular coagulation (PDIC) that causes microvascular dysfunction, which can result in organ failure. Rapid diagnosis of PDIC is a major challenge in clinical medicine. Many hemostasis parameters are available and the question arises, which of them, especially which of the new ones, can help to start a life rescuing treatment in time. The aim of this thesis was to study markers of cell destruction and hemostasis activation in order to improve the rapid laboratory diagnosis of early severe sepsis. The alterations of hemostasis in septic patients compared to normal plasma were analysed. Plasma of intensive care patients is very unstable. Therefore, in this study EDTA-plasma of intensive care patients or of healthy donors (control group) was stabilized for the first time by supramolar concentrations of arginine before freezing/thawing and analysis. Established markers of PDIC are the thrombocyte count, antithrombin III-activity, fibrinogen- and D-dimer-concentration. The present study showed that quantification in plasma of the in vivo generated circulating amidolytic thrombin activity, fibrinogenfunction/-antigen ratio, tissue factor, sL-selectin, and endotoxin reactivity add much more important information about the pathophysiology of severe sepsis and enable a rapid diagnosis of early sepsis. urn:nbn:de:hebis:04-z2010-06762 Weiste, Bettina Weiste Bettina ths Dr. Stief Thomas Stief, Thomas (Dr.) Philipps-Universität Marburg
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