1. 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):
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: