title: Increased fibrin formation and impaired fibrinolytic capacity in severe chronic kidney disease.
abstract: Chronic kidney disease (CKD) is associated with a concurrent increased risk of thrombosis and bleeding. We aimed to investigate whether CKD is associated with increased fibrin formation, impaired fibrin degradation, or both. Twenty-one patients with CKD stage 4 (CKD 4), 15 haemodialysis patients, and 13 controls (C) without kidney disease were studied. We used a global assay to determine fibrin formation and degradation in plasma. Fibrin turbidity was measured over time to obtain a value of the coagulation activation profile (Cp) and the fibrinolysis activation profile (Fp), and the amount of fibrin formed, termed fibrin optical density sum (fibrin OD-sum). We used scanning electron microscopy (SEM) to visualize the fibrin network. Plasminogen activator inhibitor type-1 antigen, thrombin-activatable fibrinolysis inhibitor activity, fibrinogen, von Willebrand factor, antithrombin, albumin, and C-reactive protein were measured in plasma. Fibrin OD-sum was significantly elevated in haemodialysis patients [312 a.u.; 278-435 (median; interquartile range); P < 0.0013] and in CKD 4 (293 a.u.; 169-434; P = 0.0119) compared with controls (115 a.u.; 82-234). SEM showed a tight fibrin network in haemodialysis and CKD 4 patients. Fp was lower in the haemodialysis group than in controls (P = 0.030). Plasminogen activator inhibitor type-1 was lower in haemodialysis patients (P = 0.034). Thrombin-activatable fibrinolysis inhibitor activity, Cp, antithrombin, and C-reactive protein did not differ between groups. Fibrinogen was significantly elevated and albumin decreased in both haemodialysis and CKD 4 patients compared with controls. Von Willebrand factor was elevated in haemodialysis patients compared with controls (P = 0.010). The prothrombotic state in severe CKD is characterized by impaired fibrinolysis in association with increased fibrin formation despite normal levels of endogenous fibrinolysis inhibitors.
authors.affiliation: aDepartment of Clinical Sciences, Division of NephrologybDepartment of Molecular Medicine and Surgery, Division of Clinical Chemistry/Coagulation ResearchcDepartment of Clinical Sciences, Division of Cardiovascular Medicine, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Josefin
authors.initials: J
authors.lastname: Mörtberg
authors.forename: Margareta
authors.initials: M
authors.lastname: Blombäck
authors.forename: Åkan
authors.initials: Å
authors.lastname: Wallén
authors.forename: Shu
authors.initials: S
authors.lastname: He
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
authors.forename: Jonas
authors.initials: J
authors.lastname: Spaak
mesh_terms: D000328:Adult; D000368:Aged; D000991:Antithrombins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D013927:Thrombosis / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000991:Antithrombins; D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D012709:Serum Albumin; D014841:von Willebrand Factor; D005337:Fibrin; D005340:Fibrinogen; D002097:C-Reactive Protein