Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model. Blood 2010 Aug 05;116(5):801-5
Date
04/23/2010Pubmed ID
20410502DOI
10.1182/blood-2009-03-213215Scopus ID
2-s2.0-77956285538 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
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.
Author List
Elmas E, Suvajac N, Jilma B, Weiler H, Borggrefe M, Dempfle CEAuthor
Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Endotoxemia
Enzyme Activation
Factor V
Fibrin
Fibrin Fibrinogen Degradation Products
Fibrinolysin
Fibrinolysis
Heterozygote
Humans
Male
Middle Aged
Plasminogen
Solubility
Time Factors
Young Adult
alpha-2-Antiplasmin
