title: Sustained release of tissue factor following thrombosis of lower limb trauma.
abstract: This study was undertaken to provide evidence for the mechanism of venous thromboembolism (VTE) in healthy patients with minor lower limb injury (fracture; Achilles tendon rupture) that was medically managed with plaster cast/brace immobilization. The Plaster Cast clinical trial provided a unique opportunity to identify the natural history of VTE using placebo-controlled patients (n = 183) with validation of the mechanism using the low-molecular-weight heparin (LMWH; reviparin)-treated patients (n = 182). Confirmed VTE in this population was associated with a burst of tissue factor release (and a minor fibrinolytic deficit) leading to thrombin generation that was sustained at least 5 weeks, greater with fractures than with soft-tissue injuries and greater with surgery than with conservative treatment. The root cause likely involves platelet/leukocyte activation (inflammation) rather than endothelial cell injury. Thromboprophylaxis with a low dose of LMWH reduced thrombin generation, with patients undergoing surgery benefitting the most.
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Loyola University Medical Center, Maywood, IL, USA Department of Pathology, Loyola University Medical Center, Maywood, IL, USA jwaleng@luc.edu.
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: Walenga
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: Phoebe C
authors.initials: PC
authors.lastname: Kaiser
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Loyola University Medical Center, Maywood, IL, USA Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: M Margaret
authors.initials: MM
authors.lastname: Prechel
authors.affiliation: Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Hoppensteadt
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Loyola University Medical Center, Maywood, IL, USA Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: Walter P
authors.initials: WP
authors.lastname: Jeske
authors.affiliation: Cardiovascular and Coagulation Therapeutics, Bayer Healthcare, Wuppertal, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Misselwitz
authors.affiliation: Global Pharmaceutical R&D, AbbVie, North Chicago, IL, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Bacher
authors.affiliation: Spine Center, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lassen
authors.affiliation: Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000125:Achilles Tendon / Q000293:injuries / Q000601:surgery; D000925:Anticoagulants / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000097:blood* / Q000601:surgery; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D006801:Humans; D035002:Lower Extremity / Q000293:injuries* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013708:Tendon Injuries / Q000097:blood* / Q000601:surgery; D013925:Thromboplastin / Q000378:metabolism*; D013997:Time Factors; D054556:Venous Thromboembolism / Q000097:blood* / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; C094240:reviparin; D013925:Thromboplastin
keywords: immobilization; low-molecular-weight heparin; lower limb; reviparin; tissue factor; trauma; venous thrombosis