Subtle renal dysfunction and bleeding risk in atrial fibrillation: symmetric dimethylarginine predicts HAS-BLED score.
Date
2015
Authors
Procter, N.E.
Ball, J.
Heresztyn, T.
Nooney, V.B.
Liu, S.
Chong, C.-R.
Ngo, D.T.
Isenberg, J.S.
Chirkov, Y.Y.
Stewart, S.
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Journal article
Citation
American Journal of Cardiovascular Disease, 2015; 5(2):101-109
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Abstract
Risk of substantial haemorrhage represents a critically important limitation to effective anti-thrombotic treatment in patients with atrial fibrillation (AF). While it is known that this risk is increased in anticoagulated patients either in the presence of anti-aggregatory drugs or concomitant renal insufficiency, there are currently few data on the potential interactions between endogenous platelet aggregability and bleeding risk.We therefore evaluated in a cohort of AF patients: (1), the putative relationship between platelet aggregability and HAS-BLED score; (2), the potential biochemical bases for such a relationship.Patients were included as part of SAFETY, a randomised controlled trial evaluating outpatient management of AF patients. Platelet response to ADP was evaluated via whole blood impedance aggregometry; clinical and biochemical correlates of platelet aggregation were sought via univariate and multivariate analysis.Platelet aggregation correlated inversely (r=-0.220, p<0.05) with HAS-BLED score. Univariate biochemical correlates of decreased platelet aggregation were plasma concentrations of symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). On multivariate analyses, plasma SDMA concentration (β=-0.318, p<0.01), platelet content of thioredoxin-interacting protein (Txnip, β=0.261, p<0.05) and plasma thrombospondin-1 (TSP-1, β=0.249, p<0.05) concentration were predictive of platelet ADP response. Consistent with previous reports, plasma SDMA concentrations were strongly and inversely correlated with estimated glomerular filtration rate (eGFR, r=-0.780, p<0.001).These data therefore suggest that (1), physiologically impaired, like pharmacologically impaired, platelet aggregability may increase bleeding risk in anticoagulated AF patients; (2), the biochemical basis for this may include impaired effects of nitric oxide (via Txnip, TSP-1) but also concomitant renal dysfunction.
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Copyright 2015 AJCD. AJCD is an open access, online only journal. Once a paper is published, the copyright will be released by the publisher under the “Creative Commons Attribution Noncommercial License”, enabling the unrestricted non-commercial use, distribution, and reproduction of the publishedarticle in any medium, provided that the original work is properly cited