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.

The Differences Value of P-Lcr, the Î’-Thromboglobulin Level, the Fibrin Degradation Products Level in Pre and Post-Hemodialysis

“…Excessive fibrinolytic activity due to chronic hemodialysis resulted in increasing levels of FDP, D-dimer and hypofibrinogenemia. 1,16,17,21 According to Malyszko et al, and Mortberg, et al, in their research found high concentrations of fibrinogen, D-dimer, thrombin -antithrombin complex, factor VII, vWF, thrombomodulin, and PAI-1 in plasma of ESRD patients. 15 Research on FDP as a marker of fibrinolytic activity in various clinical manifestations is still rare.…”

“…15 Research on FDP as a marker of fibrinolytic activity in various clinical manifestations is still rare. 2,16 Hyperactive platelets caused by hemodialysis can lead to bleeding and thrombosis thus increasing morbidity and mortality. Prevention of hemostasis disorders is expected to extend the life of people with ESRD, so the presence of hypercoagulable markers of thrombosis in patients with uremia is warranted.…”

“…14 Malyszko et al and Mortberg et al in a research found a high concentrations of fibrinogen, D-dimer, thrombin-antithrombin complex, factor VII, vWF, trombomodulin, and PAI-1 (Plasminogen Activating Inhibitor-1) in plasma of ESRD patients. 15,16 Prevention of hemostasis function disorders have been studied extending the lifetime of the ESRD patient in varying conditions. Therefore, it is necessary to investigate thrombosis initial marker in patients undergoing hemodialysis at a cost of more simple.…”

“…Therefore, it is necessary to investigate thrombosis initial marker in patients undergoing hemodialysis at a cost of more simple. 2,16,17 This study aimed to prove the difference between P-LCR, β-thromboglobulin level, FDP level and creatinine level between pre and post-hemodialysis.…”

In Reply

“…Hui and Yu also alluded that our study did not explore the functions of the whole set of serum coagulant components on AKI from a “broader view, other than focusing on the single variable of platelet count.” Again, in support of their statement, they reference two studies conducted in nonsurgical populations- one on increased fibrin formation and impaired fibrinolysis capacity in severe chronic kidney disease, 10 and the other, on the role of tissue factor and coagulation factor VII levels in patients with acute myocardial infarction. 11 We are not aware of any studies to date to indicate that increased fibrin formation, impaired fibrinolysis capacity, tissue factor or coagulation factor VII levels play a significant role in the development of postoperative AKI after cardiac surgery.…”