Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function

• Published in: Thrombosis research 2008-01, Vol.123 (2), p.374-380
• Main Authors: Adams, M.J, Irish, A.B, Watts, G.F, Oostryck, R, Dogra, G.K
• Format: Article
• Language: English
• Subjects: Aged; Antigens - physiology; Antithrombin III - physiology; Biological and medical sciences; Biological Phenomena; Biomarkers - blood; Blood and lymphatic vessels; Blood coagulation; Blood Coagulation - physiology; Cardiology. Vascular system; Chronic kidney disease; Creatinine - blood; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; E-Selectin - blood; Endothelium; Endothelium, Vascular - physiology; Factor VII - physiology; Factor X - physiology; Female; Hematology, Oncology and Palliative Medicine; Humans; Interleukin-6 - blood; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - physiopathology; Male; Medical sciences; Middle Aged; Peptide Fragments - physiology; Protein S - metabolism; Prothrombin - physiology; Renal Dialysis - adverse effects; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Solubility; Thrombin generation; Thrombomodulin - blood; Thrombophilia - complications; Thrombophilia - physiopathology; Thromboplastin - physiology; Tissue factor
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2008.03.024

Abstract Introduction Patients with chronic kidney disease exhibit features of a hypercoagulable state and have endothelial dysfunction, which may contribute to their increased cardiovascular risk. We examined the relationship between coagulation activation and vascular function in patients with chronic kidney disease. Materials and Methods We measured parameters of the tissue factor pathway of blood coagulation (tissue factor, factor VIIc and factor X); natural inhibitors (tissue factor pathway inhibitor, protein C, free and total protein S, antithrombin III) and markers of coagulation activation (thrombin-antithrombin complexes, prothrombin fragment 1 + 2) in 66 stage 4&5 chronic kidney disease patients and 36 healthy controls. Their relationship with markers of vascular function (flow mediated dilatation, soluble E-selectin and thrombomodulin) and a mediator of inflammation (interleukin-6) was determined. Results Up-regulation of the tissue factor pathway (increased tissue factor and factor VIIc), increased prothrombin fragment 1 + 2 and significant reductions in antithrombin III and the ratio of free protein S: total protein S were found in patients compared to healthy controls. Increased tissue factor antigen was significantly and independently correlated with creatinine and interleukin-6 (P < 0.001). Factor X and antithrombin III were both reduced in chronic kidney disease and correlated (r = 0.58; P < 0.001). Changes in coagulation and anti-coagulation were independent of all measures of endothelial function. Conclusions Significant activation of the TF pathway of coagulation and depletion or reduction of some natural anticoagulants in chronic kidney disease was correlated with the degree of renal dysfunction, but not correlated with the abnormalities of vascular function. These data are consistent with a hypercoagulable state in chronic kidney disease that may be independent of endothelial based regulation but associated with an inflammatory state.