The Use of Clot Strength as a Predictor of Thrombosis in Peripheral Artery Disease.

OBJECTIVES: Graft/stent thrombosis is the leading cause of amputation in patients over 60, and while dual antiplatelet therapy is the standard of care, there is a significant variability in platelet response and limited guidance on measuring effectiveness. Thromboelastography with platelet mapping (TEG-PM) can objectively detail an individual's coagulation profile, namely the strength of the clot and its response to antiplatelet medication. Although TEG-PM has been used for predicting postoperative bleeding and assessing platelet dysfunction in TBI, its application in thrombosis diseases such as peripheral artery disease (PAD) remains unexplored. The aim of this observational study was to determine if objective measures of clot strength could predict a high clinical risk of thrombosis. METHODS: Patients > 60 years with peripheral artery disease (PAD) undergoing revascularization were prospectively evaluated from 2021-2023. They were clinically followed for one year to detect any thrombotic events. TEG-PM was used to objectively evaluate coagulation profiles in patients at 1, 3, 6, and 9 months. These follow-up periods were chosen based on studies showing that 1-3 month intervals in the first year after lower extremity revascularization (LER) optimize therapy and risk control. The TEG-PM data preceding a thrombotic/stenotic event in patients with thrombosis was compared to the last known well TEG-PM event in those without a thrombotic/stenotic event. We stratified the groups based on the occurrence of thrombosis/stenotic events. Descriptive statistics were applied to characterize each group and a chi-square test was conducted to assess the variance between both groups. An unpaired t-test was ran to identify differences in platelet function. ROC analysis was performed to determine the optimal TEG-PM cutoff for predicting a higher risk of thrombosis. RESULTS: One hundred and fifty-eight patients were analyzed, from whom 28 (17.7%) experienced a thrombotic event. The thrombosis cohort exhibited significantly greater MAADP, MAFibrin, and MAThrombin [50.2 vs. 40.0, p<0.05], [18.19 vs. 14.64, p<0.05] and [63.8 vs. 58.5, p<0.05] respectively indicative of greater clot strength. By ROC analysis, the optimal predictor cutoff for MAADP, indicating a higher risk of thrombosis, was >42mm [p<0.05] with 82% sensitivity and 50% specificity. CONCLUSIONS: An increase in clot strength was found to be predictive of thrombosis/stenosis within 30 days. Using a MAADP cutoff greater than 42mm might serve as an alternative approach to tailor the use of antiplatelet medication, potentially reducing the risk of thrombosis.

The impact of sex on platelet responses to aspirin in patients with peripheral artery disease.

Women with peripheral artery disease (PAD) have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment for PAD to reduce the risk of arterial thrombosis, but platelets in women may have a variable response to this standard of care compared to men. 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 real-time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG-PM in patients with PAD on aspirin post-revascularization for PAD. All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex, demographics, medications, procedure type, and outcomes were documented. Serial perioperative TEG-PM assays (1, 3, and 6 months) were performed up to 6 months postoperatively and platelet function was evaluated in both groups. Statistical analysis between women and men was performed to identify sex-specific differences in platelet function. Over the study period, a total of 303 patients were enrolled. Of this cohort, 149 patients met the study criteria and 266 samples were analyzed; 52 (34.89%) were women and 97 (65.11%) were men. In the platelet mapping assay, women showed significantly greater MAActF and MAAA, than men (16.66 vs. 14.94, p < .03 and 37.26 vs. 32.38, p < .01, respectively) indicating stronger thrombotic propensity. Additionally, platelet inhibition was significantly lower in women compared to men (52.95% vs. 61.65%, p < .05). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men (4 vs. 1, p < .05). There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition and displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve an equivalent therapeutic effect.

Platelet function testing and clinical outcomes in peripheral arterial disease: Systematic review and narrative synthesis.

OBJECTIVE: This systematic review aims to comprehensively assess the contemporary literature on platelet function testing (PFT) in individuals undergoing revascularization therapy for peripheral arterial disease (PAD). The goal is to identify whether PFT can aid in detecting antiplatelet resistance, predicting post-procedural thrombotic complications, and informing tailored treatment strategies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review was conducted using PubMed databases. Search terms included relevant medical subject headings (MeSH) terms. Eligible articles published in English between 1990 and 2023 were analyzed. Studies that examined PFT outcomes in patients with PAD after lower extremity revascularization were included. RESULTS: Ten studies met the inclusion criteria. Various PFT methods were used, including thromboelastography with platelet mapping, multiplate analyzer, Cytochrome P450 2C19 testing, VerifyNow, corrected whole blood aggregometry, platelet function analyzer-100, and light transmission aggregometry. PFT identified individuals who were resistant or non-sensitive to antiplatelet therapy, with such patients facing increased risks of graft/stent thrombosis, amputation, and reintervention. However, substantial heterogeneity in surgical procedures, drug regimens, and testing methods was observed among the studies. CONCLUSIONS: PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization. However, heterogeneity of data and methods underlines the need for standardized protocols and consensus-building among PFTs. Enhancing clinical utility and reliability could help optimize antiplatelet thromboprophylaxis, minimize thrombotic complications, and improve treatment strategies in vascular surgery. Further research is necessary to solidify the role of PFTs in guiding antiplatelet therapy post-revascularization in patients with PAD.

Atorvastatin Effect on Clopidogrel Efficacy in Patients with Peripheral Artery Disease.

BACKGROUND: Both clopidogrel and atorvastatin metabolism are rooted in hepatic cytochrome p450 activation. There are published reports of atorvastatin interfering with clopidogrel metabolism by inhibiting the activation of clopidogrel. This in turn would decrease the therapeutic effect of clopidogrel potentially resulting in an increase in thrombotic events in patients who are taking both medications. The emergence of viscoelastic assays, such as Thromboelastography with platelet mapping (TEG-PM), has been utilized to identify prothrombotic states and may provide insight into a patient's microvascular coagulation profile. The aim of this prospective, observational study was to delineate the differences in platelet function between patients on clopidogrel alone versus those on clopidogrel and atorvastatin in patients that are undergoing peripheral revascularization. METHODS: All patients undergoing revascularization between December 2020 and August 2022 were prospectively evaluated. Patients on clopidogrel and atorvastatin were compared to those on clopidogrel alone. Serial perioperative TEG-PM analysis was performed up to 6 months postoperatively and the platelet function in terms of percent inhibition was evaluated in both groups. Statistical analysis was performed using unpaired t-test to identify differences in platelet function. RESULTS: Over the study period, a total of 182 patients were enrolled. Of this cohort 72 patients met study criteria. 87 samples from the 72 patients were analyzed. 31 (43.05%) patients were on clopidogrel alone and 41 (56.94%) were on clopidogrel and atorvastatin. Patients on clopidogrel alone showed significantly greater platelet inhibition compared to those on clopidogrel and atorvastatin [49.01% vs. 34.54%, P = 0.03]. There was no statistical difference in platelet inhibition between groups in terms of aspirin use alone versus aspirin and atorvastatin. CONCLUSIONS: Patients on clopidogrel and atorvastatin showed significantly less platelet inhibition compared to those on clopidogrel alone, supporting the concept that atorvastatin may interfere with the therapeutic effect of clopidogrel. Patients taking atorvastatin may require an alternative antiplatelet therapy regimen that does not include clopidogrel to achieve adequate thromboprophylaxis.