Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model

• Verfasst von: Elmas, Elif [VerfasserIn]
• Verfasst von: Suvajac, Nenad [VerfasserIn]
• Verfasst von: Jilma, Bernd [VerfasserIn]
• Verfasst von: Weiler, Hartmut [VerfasserIn]
• Verfasst von: Borggrefe, Martin [VerfasserIn]
• Verfasst von: Dempfle, Carl-Erik [VerfasserIn]
• Titel: Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model
• Verf.angabe: Elif Elmas, Nenad Suvajac, Bernd Jilma, Hartmut Weiler, Martin Borggrefe, and Carl-Erik Dempfle
• E-Jahr: 2010
• Jahr: April 21, 2010
• Umfang: 5 S.
• Fussnoten: Gesehen am 22.05.2023
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2010
• Band/Heft Quelle: 116(2010), 5 vom: Aug., Seite 801-805
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood-2009-03-213215
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1845899776

Abstract

Disseminated intravascular coagulation in sepsis is associated with microvascular thrombosis and organ dysfunction. It was expected that prothrombotic disposition such as factor V Leiden (FVL) mutation would worsen clinical outcome. Astonishingly, clinical trial and animal experimental data indicate that FVL can be associated with improved survival. This study investigated the effect of FVL on the response to endotoxin of the coagulation and fibrinolytic system in humans. Fourteen healthy male subjects without FVL and 15 healthy males with heterozygous FVL received an intravenous bolus dose of endotoxin, 2 ng/kg of body weight. Blood samples were drawn before and 1, 2, 4, 6, and 24 hours after administration of the endotoxin. Injection of endotoxin led to a more pronounced increase in soluble fibrin in patients with FVL than in controls. Patients with FVL displayed a more sustained increase in plasmin-plasmin inhibitor complex after 4, 6, and 24 hours. Patients with FVL mutation also displayed higher levels of D-dimer and fibrinogen-fibrin degradation products in plasma after 24 hours. Patients with FVL generate higher levels of soluble fibrin, which may serve as cofactor in tissue plasminogen activator-induced plasminogen activation, leading to a more sustained activation of fibrinolysis with production of more fibrinogen- and fibrin-degradation products.