title: Enhanced lysis and accelerated establishment of viscoelastic properties of fibrin clots are associated with pulmonary embolism.
abstract: The factors that contribute to pulmonary embolism (PE), a potentially fatal complication of deep vein thrombosis (DVT), remain poorly understood. Whereas fibrin clot structure and functional properties have been implicated in the pathology of venous thromboembolism and the risk for cardiovascular complications, their significance in PE remains uncertain. Therefore, we systematically compared and quantified clot formation and lysis time, plasminogen levels, viscoelastic properties, activated factor XIII cross-linking, and fibrin clot structure in isolated DVT and PE subjects. Clots made from plasma of PE subjects showed faster clot lysis times with no differences in lag time, rate of clot formation, or maximum absorbance of turbidity compared with DVT. Differences in lysis times were not due to alterations in plasminogen levels. Compared with DVT, clots derived from PE subjects showed accelerated establishment of viscoelastic properties, documented by a decrease in lag time and an increase in the rate of viscoelastic property formation. The rate and extent of fibrin cross-linking by activated factor XIII were similar between clots from DVT and PE subjects. Electron microscopy revealed that plasma fibrin clots from PE subjects exhibited lower fiber density compared with those from DVT subjects. These data suggest that clot structure and functional properties differ between DVT and PE subjects and provide insights into mechanisms that may regulate embolization.
authors.affiliation: Children's Hospital of Philadelphia Research Institute, 417 Abramson Research Center, 421 Curie Blvd., Philadelphia, PA 19104-4318. ischirop@mail.med.upenn.edu.
authors.forename: Marissa R
authors.initials: MR
authors.lastname: Martinez
authors.forename: Adam
authors.initials: A
authors.lastname: Cuker
authors.forename: Angela M
authors.initials: AM
authors.lastname: Mills
authors.forename: Amanda
authors.initials: A
authors.lastname: Crichlow
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lightfoot
authors.forename: Irina N
authors.initials: IN
authors.lastname: Chernysh
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Nagaswami
authors.forename: John W
authors.initials: JW
authors.lastname: Weisel
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000378:metabolism; D004548:Elasticity; D026122:Factor XIIIa / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D010958:Plasminogen / Q000378:metabolism; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000209:etiology / Q000378:metabolism*; D020246:Venous Thrombosis / Q000150:complications
chemical_list: D003432:Cross-Linking Reagents; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D026122:Factor XIIIa
keywords: deep vein thrombosis; fibrin; lysis; pulmonary embolism