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.