Hämostaseologische Aspekte des perioperativen Blutmanagements

Zusammenfassung

Die Aktivierung der plasmatischen Gerinnungskaskade wird durch das Vorhandensein des Gewebefaktors (tissue factor, TF) auf der Oberfläche von Zellen und subendothelialen Strukturen verursacht. Die Beendigung des Gerinnungsvorganges nach z. B. Verletzungen ist ebenso überlebenswichtig wie ein schnelles Aktivieren der Gerinnungskaskade. Darüber hinaus sind physiologische Antikoagulationsmechanismen erforderlich, um dem gerinnungsaktivierenden Effekt des verlangsamten Blutstromes und des ungünstigeren Verhältnisses von Reibungsoberfläche (Endothel) und durchströmendem Blut in der Mikrozirkulation Rechnung zu tragen. Dabei handelt es sich um das Antithrombin-Glykosaminoglykan und das Thrombin- Thrombomodulin-Protein C-System. Bei einer statischen Gerinnungsstörung besteht in der Regel eine Verminderung eines einzelnen oder einer bestimmten Gruppe von Gerinnungsfaktoren oder -inhibitoren, die im zeitlichen Verlauf unverändert bleibt. Bei der dynamischen Gerinnungsstörung führt ein pathologischer prokoagulatorischer Stimulus (z. B. Trauma, Schockzustand, Endotoxin in der Sepsis, Schlangenbiss) zu einer überschießenden Aktivierung des Gerinnungssystems und damit zu einer Umsatzsteigerung der Gerinnungsfaktoren. Statische Gerinnungsstörungen können mit therapeutischer Zurückhaltung gesehen werden. Dynamische Gerinnungsstörungen können nach chirurgischer Blutstillung zuerst durch eine Inhibitorsubstitution mittels AT korrigiert werden, begleitend sollten gerinnungsaktive Frischplasmen transfundiert werden. Bei auch mit Antifibrinolytika nicht behebbaren diffusen Blutungszuständen lässt sich eine probatorische Therapie mit einem rekombinanten F VII a- Konzentrat vertreten. Zu den künftigen Perspektiven zur Verringerung des Fremdblutkomponentenverbrauchs gehören die intraoperative Gewinnung von autologem gerinnungsaktiven Frischplasma, liposomverpackte Gemische hämostaseologisch aktiver Oberflächenrezeptoren der Thrombozyten oder inhalativ applizierbare Liposome mit Thrombomodulin sowie sense- und antisense- Oligonukleotide für Gewebefaktor.

Abstract

Recent studies in humans have shown that tissue factor on the surface of endothelial cells, monocytes, or subendothelial structures sparks plasmatic coagulation. In vivo, there is no functional separation of an “endogenous” and “exogenous” pathway of the coagulation cascade. However, global laboratory tests run along such pathways due to preincubation with specific activators and, hence, allow localization of inherited coagulation defects. Coagulation inhibitors such as antithrombin or activated protein C are accelerated in their activity by cell surface glycoproteins and almost completely inactivate procoagulant activity in the microcirculation. Antithrombin binds to endothelial glycosaminoglycans and then significantly increases anticoagulant activity. Protein C is activated by the thrombin-thrombomodulin-complex and inactivates factors V a and VIII a, respectively. Additionally, activated protein C has a profibrinolytic effect. Both systems physiologically counteract the procoagulant transformation of endothelial and monocyte cell surfaces which occurs in critically ill patients due to induction of tissue factor, suppression of thrombomodulin, and removal of glycosaminoglycans from the cell surface. The distinction of statical and dynamical coagulation disorders is useful since statical disorders seldomly require therapeutic interventions although global laboratory tests may continuously deteriorate. Dynamical disorders are symptoms of an underlying disease, and consumption coagulopathy with disseminated fibrin deposition and oozing occurs when coagulation turnover cannot be stopped. Antithrombin substitution is a well documented therapeutic option along with fresh frozen plasma and erythrocyte concentrate transfusion for blood substitution. Recent case reports in patients with irreversible bleeding complications favour the application of a recombinant factor VII concentrate. A rising perspective to decrease the use of heterologous blood and blood products may be intraoperative plasma retransfusion. The quality of such plasma undergoing consecutive filtration steps has to be clinically studied. The application of a synthetic platelet substitute, the “plateletsome”, containing platelet glycoproteins led to significantly improved haemostasis without generating systemic procoagulant activity. In a far future, procoagulant cell surface transformation may be influenced by topic application of inhaled thrombomodulin loaded liposomes or by sense or antisense oligonucleotides inducing thrombomodulin expression or suppressing tissue factor expression, respectively.

Schlüsselwörter

Blutgerinnung - Blutung - Gerinnungsstörung - Gerinnungsfaktoren - perioperatives Management - Verbrauchskoagulopathie - Transfusion

Key words

Bleeding - coagulation - coagulation disorders - coagulation factors - perioperative blood management - transfusion

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