Increased fibrin formation and impaired fibrinolytic capacity in severe chronic kidney disease.

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 (C-p) and the fibrinolysis activation profile (F-p), 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. F-p 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, C-p, 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. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.