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Auswirkungen der extracorporalen Zirkulation (EKZ) auf das Gerinnungssystem und die Fibrinolysekaskade

Mögliche Korrelationen zu Inflammationsreaktionen

The influence of extracorporeal circulation (ECC) on the coagulation and the fibrinolytic cascade—correlation to inflammatory reactions?

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Zeitschrift für Herz-, Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Hintergrund

Der Einsatz der extracorporalen Zirkulation in der offenen Herzchirurgie bedingt Veränderungen im Bereich der Hämostase. Der Kontakt zu Fremdoberflächen wird häufig für akute mit Inflammationsreaktionen vergleichbare Veränderungen verantwortlich gemacht. Bei einigen Patienten scheint dieses Post-Perfusions-Syndrom (PPS) der Anfang eines SIRS zu sein. Deshalb haben wir in der vorliegenden Studie die Kaskaden des Gerinnungssystems und der Fibrinolyse unter und nach Bedingungen der EKZ unter besonderer Berücksichtigung von Prostazyklin und Aprotinin untersucht.

Methoden

In einer prospektiv randomisierten Studie wurden 40 Patienten, die sich einer aorto-coronaren Bypassoperation unterziehen mussten, in 4 Gruppen a 10 Patienten jeweils abhängig von der Behandlung mit PGI2 und/oder Aprotinin eingeteilt. Pro Patient wurden perioperativ 6 Blutproben entnommen und die Entzündungsparameter sowie die Gerinnungs- und Fibrinolyseparameter bestimmt.

Ergebnisse

Signifikante Unterschiede konnten für Thrombozyten, tPA, D-Dimere, PAI-, α2-antiplasmin- und die Plasminogen-Aktivität ermittelt werden. In der Aprotinin-Gruppe wurden significant geringere Werte für TAT-Komplexe während der EKZ bestimmt. Erniedrigte Werte von PF4 und β-TG während EKZ zeigten sich nur bei Patienten mit PGI2- und Aprotinin-Behandlung. In allen Untersuchungen zeigten sich erhöhte Werte für Elastase in Korrelation mit abfallender AT-III-Aktivität. Bei Patienten mit einem postoperativen PPS oder SIRS zeigten sich signifikant höhere Elastase-Werte.

Schlussfolgerungen

Die Aktivierung der Fibrinolyse während EKZ scheint eine der wesentlichen Ursachen von Blutungskomplikationen darzustellen. Prostazyklin wirkt ausschließlich auf die Thrombozyten selbst, im Gegensatz dazu wurden Aprotinin-Gaben von Inhibitionen der Thrombin-Aktivierung und Fibrinolyse sowie Thrombozyten-protektiven Effekten begleitet. CPB verursacht die Freisetzung von Elastase; diese kann somit als Indikator von Inflammationsreaktionen herangezogen werden. Dies steht in Korrelation zu der beobachteten AT-III-Verminderung; daher erscheinen AT-III-Substitutionen in solchen Fällen sinnvoll.

Summary

Background

Open heart surgery with cardiopulmonary bypass causes changes in hemostasis. Artificial surfaces are bioincompatible and thus may initiate a reaction similar to an acute inflammation. In some patients this “post-perfusion syndrome” (PPS), which includes changes in hemostasis, is the beginning of a SIRS. Thus, it was the aim of our study to investigate the cascade of coagulation and fibrinolysis during and after ECC, especially a modification by prostacyclin and aprotinin.

Methods

In a prospective study 40 patients undergoing aortocoronary bypass grafting were divided into 4 groups of 10 patients, depending on their drug administration with PGI2 and/or aprotinin. Six blood samples were taken from every patient perioperatively and analyzed for parameters of inflammation, coagulation and fibrinolysis.

Results

Significant differences between the 4 groups could be found for platelets, tPA, D-dimers, PAI-, α2-antiplasmin- and plasminogen-activity. Furthermore, there were significantly lower vales for TAT complexes during ECC in the aprotinin group. PF4 and β-TG were significantly decreased during ECC only in patients with PGI2 and aprotinin. Levels of plasma elastase increased significantly in all intra- and postoperative blood samples with a direct correlation to decreasing antithrombin III-levels. In patients with a postoperative PPS or SIRS, intraoperative elastase levels were significantly higher.

Conclusions

During ECC the activation of fibrinolysis seems to be of importance for bleeding complications. Prostacyclin only acts on thrombocytes directly, whereas the application of aprotinin was followed by inhibition of thrombin activation and fibrinolysis and by a protecting effect on thrombocytes. CPB initiates an elastase release, which seems to be an indicator of inflammatory reactions. As elastase release could be correlated to AT III reduction, the use of AT III seems to be useful in selected patients.

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Authors and Affiliations

  1. Klinik für Herz- und Thoraxchirurgie, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany

    J. Litmathe, U. Boeken, P. Feindt & E. Gams

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  1. J. Litmathe
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  2. U. Boeken
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  3. P. Feindt
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  4. E. Gams
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Correspondence to J. Litmathe.

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Litmathe, J., Boeken, U., Feindt, P. et al. Auswirkungen der extracorporalen Zirkulation (EKZ) auf das Gerinnungssystem und die Fibrinolysekaskade. Z Herz-, Thorax-, Gefäßchir 18, 222–230 (2004). https://doi.org/10.1007/s00398-004-0459-8

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