Nathan Ek Procter1, Jocasta Ball2, Tamila Heresztyn1, Vivek B Nooney3, Saifei Liu1, Cher-Rin Chong1, Doan Tm Ngo1, Jeffrey S Isenberg4, Yuliy Y Chirkov1, Simon Stewart5, John D Horowitz1. 1. Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide Australia. 2. Centre for The Heart and Mind, Mary MacKillop Institute for Health Research, Australian Catholic University Melbourne, Australia. 3. Basil Hetzel Institute, The Queen Elizabeth Hospital, University of South Australia Australia. 4. Heart, Lung, Blood and Vascular Medicine Institute, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Pittsburgh, Pennsylvania, U.S. 5. National Health and Medical Research Council (NHMRC) Centre of Excellence to Reduce Inequality in Heart Disease, Mary MacKillop Institute for Health Research, Australian Catholic University Melbourne, Australia ; Baker IDI Heart and Diabetes Institute Melbourne, Australia.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVE: We therefore evaluated in a cohort of AFpatients: (1), the putative relationship between platelet aggregability and HAS-BLED score; (2), the potential biochemical bases for such a relationship. METHODS:Patients were included as part of SAFETY, a randomised controlled trial evaluating outpatient management of AFpatients. 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. RESULTS: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). CONCLUSIONS: These data therefore suggest that (1), physiologically impaired, like pharmacologically impaired, platelet aggregability may increase bleeding risk in anticoagulated AFpatients; (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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