AN EARLY COAGULATION FACTOR-DOMINANT HYPERCOAGULABILITY IS FOLLOWED BY A PROLONGED PLATELET-DOMINANT HYPERCOAGULABILITY IN PATIENTS WITH HIP FRACTURE

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The risk for venous thromboembolism (VTE) after hip fracture surgery (HFS) is amongst the highest for all surgical procedures. Despite thromboprophylaxis, a sub-analysis of the FAITH and HEALTH trials demonstrated a 2.5% VTE rate. More concerning, 45.3% of VTE events were diagnosed more than six weeks post-fracture, beyond currently recommended duration of thromboprophylaxis. Thrombelastography (TEG) is a whole-blood viscoelastic hemostatic assay which provides a comprehensive real-time analysis of hemostasis, from clot initiation to fibrinolysis. As patients with hip fracture continue to suffer from debilitating VTE events, TEG analysis may provide valuable information on coagulation kinetics responsible for hypercoagulability to guide thromboprophylaxis regimens. The objective of this study was to determine the timing of different phases of coagulation responsible for hypercoagulability in patients after HFS. In this prospective cohort study, TEG analysis was performed in patients with hip fracture every 24-hours from admission until post-operative day (POD) 5, then at 2-week, 6-week, and 3-month post-operative follow-up. Hypercoagulability was defined by TEG parameter values beyond the reference range for clot initiation [Activated Clotting Time (ACT), Reaction-time (R-time)], clot propagation [Kinetic-time (K-time) and Alpha-angle (a-angle)]. A hypercoagulable threshold of >5 mm determined a priori was used for Maximal Amplitude (MA), a measure of platelet contribution to maximal clot strength. One-sample t-tests were performed at follow-up timepoints when the TEG parameter was beyond reference range and paired t-test was performed to compare follow-up timepoints to admission values. All statistical tests were two-sided and p-values < 0.05 were considered statistically significant. In total, 121 patients with a median age of 81.0 (IQR 71–87) were included. ACT and R-time demonstrated progressively shorter time to clot initiation compared to admission values until POD4 [(ACT mean difference=11.7sec, SEM=2.1; p<0.001), (R-time mean difference=0.13min, SEM=0.02; p<0.001)] signifying an increased coagulation factor dominant hypercoagulability in the early post-operative period. Maximal Amplitude values demonstrated a peak two weeks post-operatively (mean MA=70.8, SD=2.7; p<0.001) and remained elevated six weeks post-operatively (mean MA=65.9, SD=4.0; p=0.04), before normalizing three months post-operatively. Symptomatic VTE events were detected in three patients (2.5%) post-operatively. All three patients demonstrated platelet-dominant hypercoagulability at the 6-week follow-up, with elevated MA values. Serial TEG analysis was able to quantify early hypercoagulability after hip fracture that is related to increased procoagulant factor activity. This finding supports early thromboprophylaxis within 24 hours of surgery and the use of anticoagulants like LMWH which target procoagulant factors. Interestingly, there was a prolonged platelet-dominant hypercoagulability which extended beyond current recommended thromboprophylaxis duration after hip fracture surgery. As patients with hip fracture continue to suffer from VTE, extended thromboprophylaxis with antiplatelet agents may be of benefit. Future studies evaluating alternative thromboprophylaxis regimens which consider targeting procoagulant factors and platelet hyperactivity for a prolonged period of time may help prevent VTE events after hip fracture surgery.

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