title: The influence of type 2 diabetes on fibrin clot properties in patients with coronary artery disease.
abstract: Type 2 diabetes mellitus (T2DM) increases the risk of coronary thrombosis and both conditions are associated with altered fibrin clot properties. However, the influence of T2DM on fibrin clot properties in patients with coronary artery disease (CAD) remains unclear. We aimed to investigate the influence of T2DM on fibrin clot properties in patients with CAD. Fibrin clot structure and fibrinolysis were investigated in 581 CAD patients (148 with T2DM) using turbidimetric assays, confocal and scanning electron microscopy. Clots made from plasma and plasma-purified fibrinogen were studied, and plasma levels of inflammatory markers were analysed. T2DM patients had increased clot maximum absorbance compared with non-diabetic patients (0.36 ± 0.1 vs 0.33 ± 0.1 au; p=0.01), displayed longer lysis time (804 [618;1002] vs 750 [624;906] seconds; p=0.03) and showed more compact fibrin structure assessed by confocal and electron microscopy. Fibrinogen levels were elevated in T2DM (p< 0.001), but clots made from purified fibrinogen showed no differences in fibrin properties in the two populations. Adjusting for fibrinogen levels, T2DM was associated with C-reactive protein and complement C3 plasma levels, with the former correlating with clot maximum absorbance (r=0.24, p< 0.0001) and the latter with lysis time (r=0.30, p< 0.0001). Independent of fibrinogen levels, females had more compact clots with prolonged lysis time compared with males (all p-values< 0.001). In conclusion, T2DM is associated with prothrombotic changes in fibrin clot properties in patients with CAD. This is related to quantitative rather than qualitative changes in fibrinogen with a possible role for inflammatory proteins.
authors.forename: S
authors.initials: S
authors.lastname: Neergaard-Petersen
authors.forename: A-M
authors.initials: AM
authors.lastname: Hvas
authors.forename: S D
authors.initials: SD
authors.lastname: Kristensen
authors.forename: E L
authors.initials: EL
authors.lastname: Grove
authors.forename: S B
authors.initials: SB
authors.lastname: Larsen
authors.forename: F
authors.initials: F
authors.lastname: Phoenix
authors.forename: Z
authors.initials: Z
authors.lastname: Kurdee
authors.forename: P J
authors.initials: PJ
authors.lastname: Grant
authors.affiliation: Ramzi Ajjan, Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, Leeds Institute for Genetics, Health and Therapeutics, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK, E-mail: r.ajjan@leeds.ac.uk.
authors.forename: R A
authors.initials: RA
authors.lastname: Ajjan
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003176:Complement C3 / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D003925:Diabetic Angiopathies / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012042:Registries; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors
chemical_list: C038245:C3 protein, human; D003176:Complement C3; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D005337:Fibrin; D005340:Fibrinogen; D002097:C-Reactive Protein; D001241:Aspirin
keywords: Fibrin clot; coronary artery disease; fibrinolysis; inflammation; type 2 diabetes mellitus