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Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation

Schweregrad des Multiorganversagens (MOV) jedoch nicht der Sepsis korreliert mit irreversibler Degranulation zirkulierender Thrombozyten

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Summary

Multiple hemostatic changes occur in sepsis and multiple organ failure (MOF). To evaluate the role of platelets in patients with sepsis and MOF, we examined changes in surface glycoproteins on circulating platelets of 14 patients with suspected sepsis and MOF. The severity of sepsis and MOF was assessed by the Elebute and APACHE II scoring systems, respectively. Using flow cytometric techniques and platelet specific monoclonal antibodies, platelet surface expression of fibrinogen receptor on GPIIb-IIIa, of von Willebrand Factor receptor GPIb, and of granule glycoproteins (thrombospondin (TSP), GMP-140, GP53) was measured. Plasma membrane expression of GPIIb-IIIa and GPIb on circulating platelets was not affected by sepsis or MOF. Septic patients, however, showed a significantly elevated fibrinogen receptor activity (LIBS1 expression) (p<0.05) that correlated with severity of disease (r=0.597, p=0.043). No significant change in surface expression of granule glycoproteins (TSP, GMP-140, GP53) was noted in septic patients. In contrast, degranulation of granule glycoproteins was significantly elevated in MOF (p<0.05) which correlated well with severity of MOF (GMP-140, r=0.611, p=0.013; TSP, r=0.643, p=0.026). We speculate that platelets in sepsis circulate in a hyperaggregable but still reversible state that results in increased risk of microthrombotic events. In the course of the disease, irreversible platelet degranulation of adhesion molecules occurs that may play an important role in the development of MOF.

Zusammenfassung

Ziel der vorliegenden Pilotstudie war es, die Thrombozytenfunktion von 14 Intensivpatienten mit unterschiedlicher Ausprägung von Sepsis und Multiorganversagen (MOV) zu untersuchen. Schweregrad der Sepsis und des MOV wurde anhand intensivmedizinischer Scoresysteme (APACHE II, Elebute) beurteilt. Die Thrombozytenfunktion wurde durch durchflußzytometrische Bestimmung von membranständigen Glykoproteinen (GPIIb-IIIa, GPIb, Thrombospondin (TSP), GMP-140, GP53) untersucht. Weder Sepsis noch MOV beeinflußten die Oberflächen-expression von GPIIb-IIIa oder GPIb. Die Aktivierung des Fibrinogenrezeptors war jedoch bei Sepsis deutlich erhöht (p<0.05) und korrelierte signifikant mit dem Schweregrad der Erkrankung (r=0,597, p=0,043). Eine signifikant gesteigerte Degranulation der Thrombozyten bei Sepsis konnte jedoch nicht beobachtet werden. Im Gegensatz dazu war die thrombozytäre Freisetzung von Granula-Glykoproteinen (TSP, GMP-140, GP53) bei MOV deutlich erhöht (p<0,05) und korrelierte mit dem Schweregrad der Erkrankung (GMP-140, r=0,611, p=0,013; TSP, r=0,643, p=0,026). Die Ergebnisse dieser Arbeit zeigen, daß Blutplättchen in Patienten mit Sepsis in einem aktivierten jedoch noch reversiblen Aggregationszustand zirkulieren (Aktivierung des Fibrinogenrezeptors), einhergehend mit einem erhöhten Risiko von Mikrothrombosen. Im Laufe der Erkrankung kann es zur gesteigerten Freisetzung und Oberflächenexpression von thrombozytären Glykoproteinen kommen, die eine entscheidende pathophysiologische Rolle in der Entwicklung von Mikrozirkulationsstörungen und MOV spielen könnten.

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Authors and Affiliations

  1. I. Medizinische Klinik, Klinikum Rechts der Isar der Technischen Universität München, Ismaningerstraße 22, D-80165, München

    M. Gawaz

  2. Medizinische Klinik I, Klinikum Großhadern der Universität München, Marchioninistraße 15, D-81377, München, Germany

    Suzanne Fateh-Moghadam,  G. Pilz,  H. J. Gurland &  K. Werdan

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  2. Suzanne Fateh-Moghadam
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Gawaz, M., Fateh-Moghadam, S., Pilz, G. et al. Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation. Infection 23, 16–23 (1995). https://doi.org/10.1007/BF01710051

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