Optimizing platelet inhibition in peripheral artery disease: A comparison of mono-antiplatelet therapy and dual-antiplatelet therapy using thromboelastography.

BACKGROUND: Antiplatelet therapy is used to prevent thrombosis in patients with peripheral artery disease (PAD) following revascularization. However, the current standard of care for these patients remains at the physician's discretion, varying from mono-antiplatelet therapy (MAPT) to dual-antiplatelet therapy (DAPT). Viscoelastic assays such as Thromboelastography with Platelet Mapping (TEG-PM) provide insight into individual coagulation profiles and measure real-time platelet function. This prospective, observational study looks at the differences in platelet function for patients on MAPT versus DAPT using TEG-PM. METHODS: Patients with PAD undergoing revascularization were prospectively evaluated between December 2020 and June 2023. TEG-PM analysis compared platelet function for patients prescribed MAPT (aspirin or clopidogrel) at the initial encounter and DAPT (aspirin and clopidogrel) at the next visit. Platelet function measured in percent inhibition was evaluated at these visits, and within-group t-tests were performed. RESULTS: Of the 195 patients enrolled, 486 samples were analyzed by TEG-PM. Sixty-four patients met the study criteria. At the initial visit, 52 patients had been prescribed aspirin, and 12 patients had been prescribed clopidogrel. For patients initially prescribed aspirin MAPT, an increase of 96.8%in the mean ADP platelet inhibition was exhibited when transitioning to DAPT [22.0% vs. 43.3%, p < .01], as well as an increase of 34.6%in the mean AA platelet inhibition when transitioning to DAPT [60.9% vs. 82.0%, p < .01]. For patients prescribed initial clopidogrel MAPT, an increase of 100% in AA platelet inhibition was exhibited on DAPT compared to the MAPT state [42.3% vs. 84.6%, p < .01]. CONCLUSIONS: Patients on DAPT showed a significant increase in platelet inhibition when compared to initial aspirin MAPT. A significant difference in AA %platelet inhibition was shown for patients on DAPT when compared to initial clopidogrel MAPT. The results show that patients may benefit from DAPT post-revascularization. Personalizing antiplatelet therapy with objective viscoelastic testing to confirm adequate treatment may be the next step in optimizing patient outcomes to reduce thrombosis in PAD patients.

Impact of Factor Xa Inhibition on Coagulation, Platelet Reactivity, and Thrombosis in Patients with Peripheral Artery Disease.

BACKGROUND: The role of thrombin in vascular pathology is a focus of investigation. The incorporation of direct Factor Xa inhibition into practice patterns is based on its theoretical dual-pathway attenuation of both thrombin generation and platelet aggregation. However, quantification of the effect of direct anti-Xa medications on platelet function is not established. Thromboelastography with platelet mapping (TEG-PM) leverages dual-pathway metrics to provide comprehensive coagulation profiles. We evaluated the effects of direct oral anticoagulants (DOACs) on coagulation and platelet function profiles and correlate these data with postoperative major adverse limb events (MALEs) in patients with PAD. METHODS: We conducted a prospective study of patients undergoing lower extremity revascularization with serial perioperative TEG-PM analysis. Patients on DOACs were compared to those not on DOACs, and stratified by concurrent mono-antiplatelet or dual-antiplatelet regimens (MAPT/DAPT). Postoperative MALE was recorded and difference in antithrombotic regimens and TEG-PM analysis compared between groups. RESULTS: Four hundred seventy-one samples from 141 patients were analyzed. Twenty-nine point five percent were reflective of circulating DOAC therapy. Compared to MAPT alone, patients on DOAC + MAPT exhibited longer time to clot formation (R-time) [7.4 (±2.4) vs. 6.7 (±2.7); P < 0.02], but less platelet inhibition. Patients on DAPT exhibited greater platelet inhibition compared to either group [23.7 (±26.9) vs. 31.0 (±28.3) vs. 42.2 (±31.2); P < 0.01]. Patients who experienced MALE were more likely to be on DOAC therapy [43.8% vs. 22.0% P = 0.02]. Thromboelastography with platelet mapping analysis from patients who experienced MALE also demonstrated longer R-time [8.6 (±3.9 vs. 7.3 (±3.0); P = 0.05] and increased maximum clot amplitude (MA) [66.7 (±4.2) vs. 61.8 (±8.2); P = 0.001]. CONCLUSIONS: Direct oral anticoagulant therapy resulted in a prolonged R-time but had no impact on platelet inhibition. Patients who experienced MALE were more often on DOACs and demonstrated an increased R-time, but also showed greater platelet reactivity evident by increased MA, suggesting DOACs may not be effective at protecting against MALE. Further research comparing DOAC therapy to a DAPT approach may add clarity to emerging multimodal antithrombotic recommendations.

Variability of antiplatelet response in patients with peripheral artery disease.

OBJECTIVE: Antiplatelet therapy has been a pillar of management for peripheral artery disease (PAD). However, a significant subset of patients with PAD will be resistant to certain antiplatelet medications and, therefore, have an increased risk of graft and/or stent thrombosis unknown to the surgeon. At present, no point-of-care testing to identity which patients will experience benefit from these medications has been incorporated into the treatment guidelines. Thromboelastography with platelet mapping affords an opportunity to evaluate real-time coagulation dynamics and platelet function. In the present prospective, observational study, we aimed to delineate the variation in response to antiplatelet therapy in patients with PAD undergoing revascularization. METHODS: All patients who were undergoing named vessel revascularization during December 2020 through April 2022 were prospectively enrolled. Platelet mapping assays were performed in three clinical phases: preoperative, postoperative inpatient, and postoperative outpatient. The distribution of platelet reactivity within patients receiving mono- vs dual antiplatelet therapy was assessed, and a between-group inferential analysis was performed. The effect of comorbidities and intervention subtype on platelet inhibition was also analyzed. RESULTS: A total of 521 platelet mapping samples from 143 individual patients were analyzed using thromboelastography with platelet mapping. We found wide variability in the distribution of platelet inhibition, with a range of 0 to 100 and an interquartile range of 37.6. Although platelet inhibition with clopidogrel 75 mg was higher on average (44.8 ± 30.2) than that with aspirin 81 mg (24.6 ± 23.7) or aspirin 325 mg (27.1 ± 26.4; P = .001), clopidogrel at 75 mg demonstrated the highest variability in response. CONCLUSIONS: These data have demonstrated significant variability in the response to both mono- and dual antiplatelet therapy in PAD patients undergoing lower extremity revascularization. Future research on the effect of this variability in response on the clinical outcomes could provide invaluable understanding of the perioperative thrombotic risk.

Utilization of Thromboelastography with Platelet Mapping to Predict Infection and Poor Wound Healing in Postoperative Vascular Patients.

BACKGROUND: Postoperative infection and wound dehiscence rates are higher than expected in peripheral artery disease and contribute significantly to limb loss and mortality. Microvascular pathology characterized by microthrombi and increased platelet aggregation have been cited as contributing factors to poor wound healing and infection. The emergence of viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's microvascular coagulation profile. This prospective, observational study aimed to determine if TEG-PM could predict poor wound healing or infection following lower extremity revascularization. METHODS: All patients undergoing revascularization between December 2020 and January 2022 were prospectively included and followed for wound complications or non-surgical site infections of the index limb. TEG-PM metrics at the first postoperative follow-up in the nonevent group was compared to the TEG-PM sample preceding the diagnosis of infection/dehiscence in the event group. Cox proportional hazards (PH) regression was used to model the predictive value of viscoelastic parameters. Cut-point analysis to determine high-risk groups was determined by performing receiver operating characteristic curve analysis. RESULTS: Of the 102 patients, 18.6% experienced infection/dehiscence. The TEG-PM sample analyzed in the event group was, on average, 19.5 days prior to the diagnosis of an event. The event group had significantly higher maximum clot amplitude (MA) (47.3 mm ± 16.0 vs. 30.6 mm ± 15.3, P < 0.01), higher platelet aggregation (71.3% ± 27.7 vs. 31.2% ± 24.0, P < 0.01), and lower platelet inhibition (28.7% ± 27.7 vs. 68.7% ± 24.1, P < 0.01). Cox PH analysis identified platelet aggregation as an independent and consistent predictor of infection (hazard ratio = 1.04, 95% confidence interval 1.03-1.06, P < 0.01). An optimal cut-point of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition identifies those with infection/dehiscence with 79.0-89.5% sensitivity. CONCLUSIONS: These are the first data to provide a quantitative link between prothrombotic viscoelastic coagulation profiles with the development of infection/dehiscence. Based on the cut-points of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition, we recommend consideration of an enhanced antimicrobial or antithrombotic approach for these high risk groups.