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Identifying Sex Dimorphism in Peripheral Artery Disease with Platelet Mapping

Published:September 01, 2022DOI:https://doi.org/10.1016/j.avsg.2022.08.006

      Highlights

      • Female patients with peripheral artery disease experience worse clinical outcomes following lower extremity revascularization and demonstrate quicker disease progression as compared to men. The reasons for this have yet to be delineated.
      • Paradoxically, traditional cardiometabolic risk factors associated with cardiovascular disease are less prevalent in females as compared to men.
      • In this cohort female patients had a significantly lower prevalence of uncontrolled diabetes, hypertension requiring multimodal pharmacologic therapy, chronic kidney disease, coronary artery disease and myocardial infarction
      • However, Platelet Mapping demonstrated consistently higher platelet reactivity in female patients, as observed overall, within the postoperative clinical phase, and despite similar antiplatelet management between groups.
      • Meaningful improvement in limb salvage rates for female patients with PAD may rely on further exploration of these viscoelastic metrics

      Abstract

      Introduction

      Clinical outcomes in women with PAD after revascularization procedures are worse as compared to men, yet there is little in the existing literature as why this may be the case. Platelet Mapping is an emerging point-of-care viscoelastic technology that measures the comprehensive properties of a blood clot, including fibrin-platelet interactions. This prospective observational study aimed to characterize the clinical and Platelet Mapping profiles of female and male patients undergoing lower extremity revascularization, and to correlate Platelet Mapping distribution to thrombotic potential.

      Methods

      All patients with a diagnosis of PAD undergoing named vessel open or endovascular revascularization to reestablish either inflow, outflow, or both, during December 2020 and January 2022 were prospectively included. Patients were followed clinically for thrombosis for up to one year. Platelet Mapping assays were performed in three clinical phases: preoperative, postoperative inpatient and postoperative outpatient. Inferential analysis between female and male patient was performed. The quartile distribution of Platelet Mapping metrics associated with thrombosis was used to infer to thrombotic potential.

      Results

      One hundred and seven patients were enrolled, of which thirty-seven (34.6%) were female. Female patients had significantly lower rates of uncontrolled diabetes [2.7% vs. 18.6%], hypertension requiring combination therapy [37.8% vs. 58.6%], CKD [27.0% vs. 51.4%], CAD [29.7% vs. 57.1%] and MI [16.2% vs. 35.7%], (all p<0.05). Platelet reactivity was significantly higher in female patients with greater platelet aggregation [75.9±23.3 vs. 63.5±28.8] and lower platelet inhibition [23.8±23.4 vs. 36.8±28.9] (all p<0.01). This trend was consistent over time when stratified by the postoperative inpatient and postoperative outpatient clinical phases. There was no statistically discernable difference in the use of antiplatelet therapy between groups, yet female patients continued to exhibit greater platelet reactivity when analyzed by type of pharmacologic regimen [platelet aggregation on monoantiplatelet therapy: 80.6±21.0 in women vs. 69.4±25.0 in men; platelet aggregation on dual antiplatelet therapy: 67.9±23.8 in women vs. 44.8±31.8 in men] (all p<0.01). 21 patients experienced postoperative graft/stent thrombosis within the study period. In relation to the overall study population, patients with thrombosis had Platelet Mapping metrics above the 50th percentile of overall platelet aggregation distribution.

      Conclusion

      There is a growing appreciation for the differences in etiology, disease progression and outcomes of cardiovascular conditions as they relate to sex. In this cohort, traditional cardiovascular risk factors were in lower prevalence in female patients. Platelet reactivity was found to be higher across clinical phases and antiplatelet regimens. High platelet reactivity was also associated with an increased incidence of thrombosis after lower extremity revascuarlization. These hypothesis-generating findings provide the basis for further exploration of sex-specific coagulation profiling in PAD patients.

      Abbreviations:

      ADP (adenosine diphosphate), BMI (body-mass index), DAPT (dual antiplatelet therapy), DM (diabetes mellitus), CAD (coronary artery disease), CKD (chronic kidney disease), MA (maximum amplitude), MAPT (mono-antiplatelet therapy), MI (myocardial infarction), PAD (peripheral arterial disease)
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