The Influence of Diabetes on Thrombotic Profiles and Outcomes on Patients with Peripheral Artery Disease.

BACKGROUND: Elevated glycated hemoglobin (HbA1c) is associated with vascular complications, including arterial thrombosis postrevascularization. However, the objective relationship between levels of HbA1c and coagulation profiles has not been established. This study aims to determine the association between specific coagulation parameters and variations in HbA1c in patients undergoing lower extremity revascularization. METHODS: Patients with peripheral artery disease undergoing revascularization were prospectively evaluated between December 2020 and July 2023. Patients were categorized based on their HbA1c levels, and their thromboelastography with platelet mapping (TEG-PM) results were compared at baseline, postoperative day 1, 1 month, 3 months and 6 months. The parameters included Maximum Amplitude (MA) with both adenosine diphosphate (ADP) and arachidonic acid (AA), as well as ADP and AA percent aggregation indicating clot strength. The study further assessed the differences in these parameters between groups with varying HbA1c levels through the use of unpaired Student's t-test for pairwise analysis and Mann-Whitney U tests. RESULTS: Among 830 samples, those with HbA1c above 6.5 demonstrated a significant increase in ADP MA (52.6 vs. 43.5, P < 0.01), AA MA (36.6 vs. 29.65, P < 0.05), clot strength without platelets activator F MA (13.10 vs. 10.80, P < 0.01), and heparin-neutralized uninhibited clot strength from thrombin activation heparinized kaolin with heparinase MA (61.10 vs. 57.70, P < 0.01) values at baseline. Postoperatively, patients with HbA1c levels greater than 6.5 had higher median functional fibrinogen citrated functional fibrinogen levels (40.95 vs. 371.35, P < 0.05) and higher formation of fibrin in response to stimulation of thrombin by tissue factor citrated functional fibrinogen MA values (22.90 vs. 20.40, P < 0.05) when measured within 36 hrs of intervention, with these trends staying consistent during the 1-month follow-up visit. The trend analysis revealed a progressive increase in ADP MA values with rising HbA1c values, indicating a unit increase in the thrombotic risk relationship. Regression analysis showed a positive relationship between HbA1c and both ADP MA (a 2.261-unit increase for each unit increase in HbA1c) and AA MA. The R-square values indicate that HbA1c only explains a small percentage of the variance in these parameters, suggesting the confounding influence of other factors contributing to thrombosis. CONCLUSIONS: Elevated HbA1c levels appear to be associated with prothrombotic tendencies in clot dynamics as measured by thromboelastography with platelet mapping, particularly in parameters related to platelet function. HbA1c explains a limited proportion of the variability in these measures, emphasizing the need for a comprehensive approach to evaluating clotting profiles in patients. This study lays the groundwork for further investigation into personalized antithrombotic strategies for patients with varying HbA1c levels.

The Impact of Sex on Antiplatelet and Anticoagulant Thromboprophylaxis in Patients With Peripheral Artery Disease Post-revascularization.

OBJECTIVE: The aim of this prospective study was to (1) objectively quantify the impact of sex on platelet function in patients with peripheral artery disease (PAD) taking antiplatelet and anticoagulant medications and (2) to develop and test a personalized, iterative algorithm that personalizes thromboprophylaxis that incorporates platelet function testing. BACKGROUND: Women with PAD have worse outcomes as compared with their male counterparts despite having lower risk factors. This health disparity may be mitigated by personalizing thromboprophylaxis regimens. METHODS: Patients undergoing revascularization were enrolled. Serial thromboelastography (TEG) and TEG with platelet mapping (TEG-PM) were performed up to 6 months postoperatively to determine objective coagulation profiles. In a subset of patients, the Antiplatelet Coagulation Exactness (ACE) algorithm was implemented, where patients were iteratively evaluated with TEG and given antiplatelet medications to maintain platelet inhibition at >29%. Statistical analysis was performed using unpaired t test, analysis of variance, and Fisher exact test. RESULTS: One hundred eighty-one patients met the study criteria. Fifty-eight (32%) patients were females and 123 (68%) were males. In the Aspirin cohort, females showed significantly greater clot strength as maximum amplitude - arachidonic acid (MA AA ) and significantly lower platelet inhibition than males: (37.26 vs 32.38, P <0.01) and (52.95% vs 61.65%, P <0.05), respectively. In the Clopidogrel cohort, females showed higher Maximum Amplitude - Adenosine Diphosphate (MA ADP ) (42.58 vs 40.35, P = not significant [NS]) compared with males. Females on dual antiplatelet therapy had higher MA ADP (39.74 vs 35.07, P =NS) and lower platelet inhibition (45.25% vs 54.99%, P= NS) than males. The incidence of thrombosis of the revascularized segment, defined as thrombotic event, was objectively identified on an arterial duplex. Women showed significantly higher thrombotic events than men (22.95% vs 10.57%, P< 0.05) on the same medication. In our pilot study, implementation of the ACE algorithm led to a significant decrease in the thrombosis rate (3%), including nonthrombotic events for females, versus the historic thrombotic rate (22%) from our institution. CONCLUSIONS: Women with PAD exhibited higher platelet reactivity, clot strength, and reduced platelet inhibition in response to antiplatelet therapy. The use of the ACE algorithm to tailor antiplatelet medication in patients with PAD post-revascularization, resulted in a significant decrease in thrombotic event rates. This may serve as an opportune way to mitigate outcome sex-specific disparities caused by inadequate thromboprophylaxis in women.

Thromboelastography with Platelet Mapping Identifies High Platelet Reactivity is Associated with Obesity, Diabetes, and Thrombotic Events.

BACKGROUND: Metabolic comorbidities such as diabetes and obesity are considered pro-inflammatory states which theoretically increase the risk of perioperative thrombotic events across many surgical disciplines. Currently, there is a paucity of objective metrics to determine such risk and ideal pharmacologic targets. Thromboelastography with Platelet Mapping (TEG-PM) provides a comprehensive profile of coagulation and may provide insight into clot dysregulation. METHODS: Patients undergoing lower extremity revascularization underwent serial TEG-PM analysis. The relationship between the TEG-PM metrics and thrombosis was evaluated. Preoperative TEG-PM samples of patients with body mass index (BMI)≥25 were compared to those of patients with a normal BMI, and between patients with diabetes mellitus (DM) and those without. RESULTS: 218 TEG-PM samples from 202 patients were analyzed. The BMI≥25 cohort showed significantly greater platelet aggregation [81.9% (±20.9) vs. 68.6% (±27.7), P < 0.01]. Patients with DM were more frequently on full-dose anticoagulation [47.7% vs. 29.7% P = 0.01] yet demonstrated increased clot strength, or adenosine diphosphate (ADP)-Maximum Clot Amplitude (MA) [49.1 (±16.1) vs. 41.5 (±17.1) and 37.7 (±19.6) vs. 31.6 (±17.4) P < 0.01]. 49 patients experienced thrombosis and exhibited greater platelet aggregation [76.6% (±17.8) vs. 66.8% (±30.4) P = 0.03] and greater ADP/arachidonic acid MA [47.1 (±16.6) vs. 41.9 (±18.8) and 38.2 (±17.8) vs. 32.5 (±19.9) both P = 0.05]. Patients who thrombosed were more often diabetic [69.5% versus 51.0% P = 0.03] and on full-dose anticoagulation [75.0% vs. 56.8% P = 0.02]. CONCLUSIONS: Patients with a BMI≥ 25 and those with diabetes demonstrated TEG-PM profiles similar to patients with thrombosis. Diabetes was independently associated with thrombosis, and full-dose anticoagulation was not protective. This suggests the potential utility of TEG-PM for thrombotic risk stratification based on metabolic factors and suggests antiplatelet agents may be effective at prevention of thrombotic events in this population.

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.

Use of Thromboelastography with Platelet Mapping to Identify Prothrombotic Coagulation Profiles in Patients with History of Cardiac Intervention Undergoing Lower Extremity Revascularization.

BACKGROUND: Patients with concomitant coronary and peripheral artery disease (CAD and PAD) are at significant risk for major adverse limb events (MALEs). Prevention of thrombosis in this population is of paramount importance. Identifying prothrombotic coagulation profiles in this cohort may facilitate targeted thromboprophylaxis. We compared coagulation profiles of those with CAD and PAD to those with PAD alone during the perioperative period of lower extremity revascularization. STUDY DESIGN: Patients undergoing lower extremity revascularization underwent thromboelastography-platelet mapping (TEG-PM) analysis preoperatively and at serial intervals for up to 6 months. Coagulation profiles of patients with significant CAD (defined as history of coronary artery bypass graft or percutaneous coronary intervention) and PAD were compared with those with PAD alone. MALE in the postoperative period was recorded. RESULTS: Four hundred seventy-seven TEG-PM samples from 114 patients were analyzed; 28.1% had a history of significant CAD. The incidence of atrial fibrillation was higher in this group. The significant CAD group had lower ADP-platelet inhibition, higher ADP-platelet aggregation, and greater maximum clot strength compared with patients with PAD alone. Patients with significant CAD were more frequently on full-dose anticoagulation, but less frequently on dual antiplatelet therapy; 28.1% of patients with significant CAD developed postoperative MALE compared with 22.9% of patients with PAD alone (p = 0.40). For both groups, patients who developed postoperative MALE demonstrated greater ADP-platelet aggregation and lower ADP-platelet inhibition. CONCLUSIONS: Patients with a history of significant CAD undergoing lower extremity revascularization demonstrated prothrombotic TEG-PM profiles, less frequent use of dual antiplatelet therapy, and greater rates of full-dose anticoagulation. Decreased platelet inhibition was also associated with postoperative MALE. This study underscores the potential utility of viscoelastic assays for coagulation profiling in complex cardiovascular patients.