Coagulation Function In Frail and Non-frail Older Inpatients With Atrial Fibrillation Nguyen Ngoc Tu1,2, Marie-Christine Morel-Kopp3, Chris Ward 3, Robert G. Cumming2, Sarah N. Hilmer 1,4   1 Department of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, Kolling Institute of Medical Research, Sydney, NSW. 2 Sydney School of Public Health, University of Sydney, Sydney, NSW 3 Northern Blood Research Centre, Kolling Institute, The University of Sydney and Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW 4 Sydney Medical School, University of Sydney, Sydney, NSW 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 All (n = 41) Frail (n = 18) Non-frail (n = 23) P Mean age (years) 85.8 ± 6.2 86.4± 6.4 86.4±6.1 0.6 Warfarin therapy 68.3% (28) 55.6% (10) 78.3% (18) 0.1 CHA2DS2-VASc score 4.7 ± 1.6 4.7 ± 1.9 4.6 ± 1.3 0.8 HAS-BLED score 2.2 ± 0.8 2.1 ± 0.8 0.7 AIM ► Overall, OHP assays in older patients not on any anticoagulants showed a trend towards hypercoagulable state compared to normal ranges in young people. ► CAT and OHP assays in patients not on any anticoagulants found that compared to non-frail patients, frail patients had : - significantly reduced fibrin generation (lower OHP, OCP and Max slope, P < 0.05) - non significant trends towards delayed clotting (longer Lag time) and lower fibrinogen plasma levels (lower OD max) ►There was no difference in clotting assays between frail and non-frail patients taking warfarin (Table 3). To comprehensively assess coagulation function and the effects of anticoagulant medications in frail and non-frail older inpatients with atrial fibrillation (AF). METHODS Table 3. Coagulation measures in frail and non-frail patients with AF 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: Calibrated Automated Thrombogram (CAT), which measures ex vivo thrombin generation potential and Overall Haemostatic Potential (OHP) assay, 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. Patients not on any anticoagulants (n = 13 ) Patients on warfarin (n = 28) Frail (n=8) Non-frail (n=5) P Frail (n=10) Non-frail (n=18) Lag time 5.4 ± 2.2 4 ± 0.6 0.2 10.1 ± 5.1 14.6 ± 14.5 0.4 ETP 1222 ± 530 1299 ± 277 0.8 482 ± 203 459 ± 275 Peak 219 ± 92 263 ± 71 103 ± 52 100 ± 59 0.9 OCP 52 ± 21 76 ± 12 0.04 43 ± 11 50 ± 22 OHP 16 ± 8 28 ± 7 0.01 10 ± 6 15 ± 9 0.1 OD max 1.1 ± 0.4 1.5 ± 0.2 1 ± 0.3 1 ± 0.4 Max slope 240 ± 149 443 ± 122 0.03 125 ± 54 175 ± 115 OFP45’ 63 ± 9 56 ± 5 75 ± 11 59 ± 25 0.09 INR 1.5 ± 0.7 1.1 ± 0.1 0.3 2.4 ± 0.5 2.2 ± 0.4 aPTT 33.7 ± 8.8 27.4 ± 1.3 38.8 ± 5.3 39 ± 5.7 B Table 1. Parameters of OHP and CAT assays Parameters Abbreviation Changes in hypercoagulable state Changes in hypocoagulable state Lag Time (time to clot, min) Lag Time ↓ ↑ Endogenous Thrombin Potential- The total amount of generated thrombin ETP Peak thrombin- the maximum thrombin concentration generated Peak Overall Coagulation Potential OCP Overall Haemostatic Potential OHP Maximum Optical Density Max OD Maximum slope of the OCP curve Max slope Overall Fibrinolysis Potential after 45 minutes OFP45min Figure 1. CAT illustrations: A. Young healthy person not on anticoagulants B. Older non-frail patient, not on any anticoagulants C. Older non-frail patient on warfarin C A Figure 2. OHP illustrations: A. Normal; B. Hypocoagulable state; C. Hypercoagulable state CONCLUSIONS OHP and CAT assays are new and useful tests for assessing overall thrombotic or haemorrhagic risk. The limited data showed that in the absence of warfarin, frail patients may have a less hypercoagulable state than non-frail older patients based on global haemostatic assays. This contradicts previous studies measuring clotting factors only. More data are needed to confirm this finding and explore potential confounders. Acknowledgements: AusAID scholarship Geoff and Elaine Penney Ageing Research Unit, RNSH Northern Blood Research Centre, Kolling Institute 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.