Coagulation Function In Frail and Non-frail Older Inpatients With Atrial Fibrillation Tu N Nguyen1,2, Dominic Pepperell3, Marie-Christine Morel-Kopp3, Christopher Ward 3, Robert G. Cumming2, Sarah N. Hilmer 1   1 Department of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia 2 Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia 3 Northern Blood Research Centre, Kolling Institute, The University of Sydney and Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW, Australia INTRODUCTION RESULTS Studies suggest that compared to non-frail, frail older people have: a hypercoagulable state1 an increased risk of bleeding complications with anticoagulant therapy2 Table 2. Participant Characteristics Variables Not anticoagulated Warfarin All (36) Frail (22) Non-frail (14) P-value All (59) Frail (26) Non-frail (33) Age, years (mean±SD) 87.28 ± 6.25 89.00 ± 5.48 84.57 ± 6.61 0.05 84.44 ± 6.05 84.65 ± 6.21 84.27 ± 6.01 0.81 CHA2DS2-VASc score 4.36 ± 1.25 4.73 ± 1.24 3.79 ± 1.05 0.17 4.76 ± 1.58 5.00 ± 1.60 4.58 ± 1.56 0.31 HAS-BLED score N/A 3.12 ± 0.95 3.08 ± 1.06 3.15 ± 0.87 0.77 INR 2.30 ± 0.59 2.27 ± 0.49 2.33 ± 0.67 0.68 AIM To comprehensively assess coagulation function and the effects of anticoagulant medications in frail and non-frail older inpatients with atrial fibrillation (AF). ► In older patients not taking any anticoagulants, there was a hypercoagulable state ( fibrin generation and  fibrinolysis) compared to normal ranges in young control group; compared to non-frail patients, frail patients had significantly reduced fibrin generation (lower OHP, OCP, OD max and Max slope, P < 0.05) (Figure 1) ►There was no difference in OHP assays between frail and non-frail patients taking warfarin (Figure 1). METHODS Inpatients aged ≥ 65 years with AF at Royal North Shore Hospital were recruited. Frailty was determined by the Reported Edmonton Frail Scale. CHA2DS2-VASc score was used to assess risk of stroke (total score ≥ 2 indicates high risk) . HAS-BLED score was used to assess risk of bleeding in patients with AF receiving anticoagulant therapy (total score ≥ 3 indicates high risk). Global coagulation tests: Overall Haemostatic Potential (OHP) assay 3, which measures ex vivo fibrin generation and fibrinolysis over time, were performed during hospitalisation (Table 1). Coagulation function was compared between frail and non-frail patients not on any anticoagulants and for those taking warfarin. Data from young healthy volunteers at the Northern Blood Research Centre, Kolling Institute of Medical Research (N=64, 63% female, mean age 37.7±13.2 male, 40.6±11.9 female) was used as control group. A B E C D Table 1. Parameters of OHP assays Parameters Abbreviation Changes in hypercoagulable state Changes in hypocoagulable state Overall Coagulation Potential OCP ↑ ↓ Overall Haemostatic Potential OHP Maximum Optical Density OD max Maximum slope of the OCP curve Max slope Overall Fibrinolysis Potential after 45 minutes OFP45 Figure 1. OHP assay parameters between groups. A: OCP B: OHP C: OD max D: Maxslope E: OFP 45min A Figure 2. OHP illustrations: A. Normal; B. Hypocoagulable state; C. Hypercoagulable state. The area under the red curve stands for OHP (overall haemostatic potential); the area under the blue curve stands for OCP (overall coagulation potential); the overall fibrinolysis potential OFP = (OCP-OHP)/OCP x100% CONCLUSIONS Reference: 1. Kanapuru, B. and W. B. Ershler (2009). "Inflammation, Coagulation, and the Pathway to Frailty." American Journal of Medicine 122(7): 605-613. 2. Johnson C, E., K. Lim W, et al. (2005). "People aged over 75 in atrial fibrillation on warfarin: the rate of major hemorrhage and stroke in more than 500 patient-years of follow-up." J Am Geriatr Soc 53: 655-659. 3. Antovic, A. (2008). "Screening haemostasis - Looking for global assays: The overall haemostasis potential (OHP) method - A possible tool for laboratory investigation of global haemostasis in both hypo- and hypercoagulable conditions." Current Vascular Pharmacology 6(3): 173-185 4. Walston, J., M. McBurnie, et al. (2002). "Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: Results from the cardiovascular health study." Archives of Internal Medicine 162(20): 2333-2341. Overall, OHP assays in older patients with AF showed increased fibrin generation and decreased fibrinolysis compared to young healthy people, consistent with hypercoagulability. In patients not taking anticoagulants, frail subjects showed reduced fibrin generating capacity compared to non-frail. This contradicts previous studies measuring clotting factors only 4. For subjects taking warfarin, no difference in OHP parameters was seen between frail and non-frail, suggesting that warfarin therapy reverses hypercoagulability in the non-frail, with less effect on the frail cohort. A major limitation of this study is that it was done in the acute care setting, in which coagulation may be influenced by acute illness and inflammation. More data are needed to confirm this finding and explore potential confounders. Acknowledgements: Australia Awards Scholarship Geoff and Elaine Penney Ageing Research Unit, RNSH, Australia Northern Blood Research Centre, Kolling Institute of Medical Research, The University of Sydney, Australia