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


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Adams, MJ 2008 , 'Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function' , Thrombosis Research, vol. 123, no. 2 , pp. 374-380 , doi: 10.1016/j.thromres.2008.03.024.

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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 (Pb0.001). Factor X and antithrombin III were both reduced in chronic kidney disease and correlated (r=0.58; Pb0.001).
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.

Item Type: Article
Authors/Creators:Adams, MJ
Keywords: Blood coagulation; Chronic kidney disease; Endothelium; Thrombin generation; Tissue factor
Journal or Publication Title: Thrombosis Research
ISSN: 0049-3848
DOI / ID Number: 10.1016/j.thromres.2008.03.024
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