Fibrinmonomer und Faktor XIII

Zusammenfassung

Unerklärte intraoperative Koagulopathien sind ein diagnostisches und therapeutisches Problem. Die Pathophysiologie intraoperativer Koagulopathien ist mannigfaltig und komplex (z. B. bestehende Gerinnungsstörungen, Dilutionskoagulopathie, medikamentöse Interaktionen). Wir haben gezeigt, dass Patienten mit elektiven chirurgischen Eingriffen und ungeklärten intraoperativen Koagulopathien bezogen auf das Ausmaß der Thrombingenerierung zu jedem Zeitpunkt (auch bereits präoperativ) signifikant weniger FXIII (und somit weniger Quervernetzungskapazität) zur Verfügung haben. Hieraus resultiert ein signifikanter Verlust an Gerinnselfestigkeit bei gleichzeitig erhöhtem Blutverlust. Aus dieser verminderten Quervernetzungskapazität erklärt sich auch die präoperativ erhöhte Fibrinmonomerkonzentration. Fibrinmonomer als Marker eines vermehrten intraoperativen Blutverlustes wurde in einer separaten klinischen Studie prospektiv validiert und bestätigt. Wichtig scheint, dass selbst der mäßige, erworbene bzw. (zur Thrombingenerierung) relative FXIII-Mangel in Situationen mit chirurgischem Stress für das hämostatische System klinisch relevant ist – dies entgegen den Erfahrungen aus der Betreuung von Patienten mit angeborenem FXIII-Mangel, der ausgeprägt sein muss, damit es spontan zu relevanten Blutungen kommt.

Patienten, die sich elektiven chirurgischen Eingriffen unterziehen müssen, keine klinisch manifeste Koagulopathie haben und dennoch eine erhöhte präoperative Fibrinmonomerkonzentration als Ausdruck einer verminderten Quervernetzungskapazität aufweisen, zeigen einen erhöhten intraoperativen Blutverlust. Dieses neue Konzept hilft, die Pathophysiologie ungeklärter intraoperativer Koagulopathien zu verstehen und erlaubt entsprechende Therapiestrategien. Weitere Studien zur frühzeitigen Erkennung und Behandlung solcher Koagulopathien sind notwendig.

Summary

Unexplained intraoperative coagulopathies continue to be a diagnostic and therapeutic dilemma. The pathophysiology behind unexplained intraoperative coagulopathies is of great variety and complexity (preexisting coagulopathies, dilutional coagulopathy, interactions of medications etc.). We have shown in prospective studies that patients undergoing elective surgery who develop “unexplained” intraoperative coagulopathies have significantly less FXIII per unit thrombin available at any point in time (i.e. already preoperatively) than patients without such coagulopathies. The consequence is a significant loss of clot firmness associated with an increase in intraoperative blood loss. Thus, these patients have less cross-linking capacity to begin with, which explains their preoperatively increased fibrin monomer concentration. The association of increased preoperative fibrin monomer and increased intraoperative blood loss was prospectively evaluated and cofirmed in a separate clinical study. It is important to note that the acquired or (compared to the amount of thrombin generated) relative F. XIII deficiency in situations with surgical stress shows early clinical relevance (even if only mild to moderate changes are present); this differs from the experiences with patients with inborn FXIII deficiency, where a pronounced deficiency must be present to have clinically significant spontaneous bleeding.

Patients undergoing elective surgery, without clinically obvious coagulopathy but increased preoperative fibrin monomer concentration (as a marker of decreased crosslinking capacity) are at risk for increased intraoperative blood loss. This new concept helps to explain the pathophysiology behind unexplained intraoperative coagulopathies and thus allows for corresponding treatment strategies. Further clinical studies for early detection and interventions in patients with such coagulopathies are necessary.

Schlüsselwörter

Thrombin - Fibrinmonomer - FXIII - Gerinnselfestigkeit - intraoperativer Blutverlust

Keywords

Thrombin - fibrin monomer - FXIII - clot firmness - intraoperative blood loss

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