BS58 Does change in renal function affect warfarin’s efficacy in patients with atrial fibrillation?

<h3>Introduction</h3> Anticoagulation use in atrial fibrillation (AF) is common, but concurrent chronic kidney disease (CKD) reduces its efficacy and potentiates the risk of bleeding. Patients with AF have a higher incidence of renal impairment and the latter predisposes to incident AF. The co-existence of both conditions leads to a higher risk for thromboembolic-related adverse events but also a paradoxical increased haemorrhagic risk with devastating consequences for the individual. Assessing the effect of renal function on plasma clot properties in anticoagulated AF patients may help explain reasons behind this. <h3>Aim</h3> To observe how progressive renal dysfunction affects plasma clot properties in AF patients on warfarin. <h3>Methods</h3> We studied 192 patients with AF on warfarin and divided them in 4 groups based on estimated glomerular filtration rate (eGFR), eGFR&gt;90 (n=30), eGFR 60–89 (n=89), eGFR 30–59 (n=59) and eGFR&lt;30 (n=14). Plasma samples were obtained from patients using venepuncture and centrifuged to prepare platelet poor plasma. Assays were performed in 96-well polystyrene microtiter plates. Reagents were diluted in standard buffer (10 mM N-2-hydroxyethylpiperazine-N’-2-ethanesulphonic acid [HEPES], pH 7.4, 150 mM NaCl). Patient plasma samples (25 %) were incubated with tissue plasminogen activator (500 ng.mL-1) for 10 minutes at 37°C before the addition of CaCl2 (7.5 mM). Either PPP reagent (2.5 %), aPPT reagent (2.5 %), or thrombin (0.5 U.mL-1) were then added to initiate coagulation. Polymerisation of fibrin in plasma was monitored (ΔOD340 nm) using a Synergy H1 hybrid multi-mode plate reader, readings were taken in 12 second intervals for up to 60 minutes. <h3>Results</h3> Comparison between the 4 groups was performed using Kruskal-Wallis test with Dunn’s post-hoc analysis and Holm-Sidak adjustment. There was no statistical difference in optical density reflecting clot turbidity or rate of clot formation between the eGFR groups (table 1). Plasma clot lysis time was noted to be significantly prolonged in patients with worsening renal function with all 3 reagents used (PPP (p=0.03), APPT (p=0.02) and thrombin (p=0.03) respectively). Time for 50% of the clot to lyse was also significantly slower with worsening renal function with PPP (p=0.04) and thrombin (p=0.02) reagents suggesting modulation of warfarin action. <h3>Conclusion</h3> Worsening renal function in AF patients on warfarin leads to increased clot lysis time, hence leading to a potentially increased risk of thrombosis. <h3>Conflict of interest</h3> None