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Thrombin Generation as a Method to Identify the Risk of Bleeding in High Clinical-Risk Patients Using Dual Antiplatelet Therapy.

ABSTRACT: Background: Patients using dual antiplatelet therapy after percutaneous coronary intervention are at risk for bleeding. It is currently unknown whether thrombin generation can be used to identify patients receiving dual antiplatelet therapy with increased bleeding risk. Objectives: To investigate whether thrombin generation measurement in plasma provides additional insight into the assessment of bleeding risk for high clinical-risk patients using dual antiplatelet therapy. Methods: Coagulation factors and thrombin generation in platelet-poor plasma were measured in 93 high clinical-risk frail patients using dual antiplatelet therapy after percutaneous coronary intervention. During 12-month follow-up, clinically relevant bleedings were reported. Thrombin generation at 1 and 6 months after percutaneous coronary intervention was compared between patients with and without bleeding events. Results: One month after percutaneous coronary intervention, the parameters of thrombin generation, endogenous thrombin potential, peak height, and velocity index were significantly lower in patients with bleeding in the following months compared to patients without bleeding. At 6 months follow-up, endogenous thrombin potential, peak height, and velocity index were still (significantly) decreased in the bleeding group as compared to non-bleeders. Thrombin generation in the patients' plasma was strongly dependent on factor II, V, and VIII activity and fibrinogen. Conclusion: High clinical-risk patients using dual antiplatelet therapy with clinically relevant bleeding during follow-up show reduced and delayed thrombin generation in platelet-poor plasma, possibly due to variation in coagulation factors. Thus, impaired thrombin-generating potential may be a "second hit" on top of dual antiplatelet therapy, increasing the bleeding risk in high clinical-risk patients. Thrombin generation has the potential to improve the identification of patients using dual antiplatelet therapy at increased risk of bleeding.

SUBMITTER: de Breet CPDM

PROVIDER: S-EPMC8224526 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Coronary artery disease (CAD) is prevalent throughout the world, with a significant impact on global health. There is a vast collection of data in the medical literature relating to the topic of dual antiplatelet therapy (DAPT) in patients considered to be at high cardiovascular (CV) risk. In order to perform a narrative review of literature regarding the use of DAPT in patients with high CV risk, PubMed, Google Scholar and Embase were searched for English-language articles from 1985 to December 2020 by using the medical subject heading terms and keywords 'antiplatelet therapy' and 'high-risk cardiovascular disease', alone or in combination. Both authors critically reviewed the design, population characteristics and results of the selected studies. The topic of DAPT in patients with high CV risk is fluid and constantly evolving. The landmark trials of CURE, TRITON-TIMI 38 and PLATO provided evidence for the optimal use of DAPT in patients after acute coronary syndrome, while the CHARISMA and MATCH trials provided guidance for clinicians for their use in patients with stable coronary artery disease. The American College of Cardiology/American Heart Association focused update, published in 2016, and the European Society of Cardiology guidelines, published in 2017, were developed to provide guidance to clinicians based on the available data at the time to be able to choose the appropriate DAPT strategy that would provide patients with the maximum clinical benefit. The management of DAPT in patients with high CV risk is a challenging task, with new data on the subject constantly being reported. Balancing ischaemic benefit with potential bleeding complications adds to the complexity of managing DAPT in these patients. With all the available data and current clinical guidelines, patients deemed at high CV risk should be considered for DAPT, taking into account individual risk:benefit ratio. In most individuals with high CV risk, the net clinical benefit favours the use of DAPT.

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Thrombin Generation as a Method to Identify the Risk of Bleeding in High Clinical-Risk Patients Using Dual Antiplatelet Therapy.

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