title: Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis.
abstract: Reduced concentration of tissue factor pathway inhibitor is a risk factor for development of deep venous thrombosis, whereas elevated concentrations of tissue factor pathway inhibitor are observed in patients with acute myocardial infarction and disseminated intravascular coagulation. Presently, we studied the association between inflammation, endothelial cell perturbation, fibrin degradation and the concentration of tissue factor pathway inhibitor in patients suspected for acute deep venous thrombosis. We determined the tissue factor pathway inhibitor -33T/C polymorphism, free and total tissue factor pathway inhibitor, C-reactive protein, von Willebrand factor and D-Dimer in 160 consecutive patients admitted to hospital with a tentative diagnosis of acute deep venous thrombosis. Deep venous thrombosis was identified in 57 patients (18 distal and 39 proximal). The distribution of the tissue factor pathway inhibitor genotypes between patients with and without deep venous thrombosis showed a trend toward significant deviation (P = 0.08). The concentrations of free and total tissue factor pathway inhibitor, C-reactive protein, von Willebrand factor and D-Dimer were significantly higher in patients with deep venous thrombosis than in patients without deep venous thrombosis (P < 0.001 for all quantities). The significant relationship between free and total tissue factor pathway inhibitor and deep venous thrombosis persisted when adjusted for the tissue factor pathway inhibitor -33T/C polymorphism, C-reactive protein, von Willebrand Factor and potentially confounding clinical conditions (P < or = 0.004), but disappeared when adjusted for D-Dimer (P > or = 0.10). We conclude that patients suffering from acute deep venous thrombosis express significantly higher concentrations of tissue factor pathway inhibitor than patients without deep venous thrombosis. The significant relationship is not associated with the -33T/C polymorphism, inflammation or endothelial cell perturbation, but is most likely related to release of tissue factor pathway inhibitor from fibrin deposits.
authors.affiliation: Institute of Public Health, University of Southern Denmark, Esbjerg, Denmark. johannes.sidelmann@svs.regionsyddanmark.dk
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Sidelmann
authors.forename: Else-Marie
authors.initials: EM
authors.lastname: Bladbjerg
authors.forename: Jørgen
authors.initials: J
authors.lastname: Gram
authors.forename: Anna-Marie B
authors.initials: AM
authors.lastname: Münster
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jespersen
mesh_terms: D000208:Acute Disease; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D008074:Lipoproteins / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics*; D014841:von Willebrand Factor
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D008074:Lipoproteins; C036309:fibrin fragment D; C051928:lipoprotein-associated coagulation inhibitor; D014841:von Willebrand Factor; D002097:C-Reactive Protein