Dynamics of Platelet Activation in Patients With Ventricular Assist Device (VAD)

Study Overview
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Brief Summary
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Consenting patients with end-stage heart failure that are implanted with/candidates for implant of a short-term/durable mechanical circulatory support device (e.g.: percutaneous microaxial pumps (Impella), extracorporeal membrane oxygenator (ECMO), Ventricular Assist Device (VAD) will be enrolled in the study. Aim of the study is to evaluate the patients' haemostatic and coagulation profile, how it interacts with the support device as well as the effect of antithrombotic drugs. From these data, it will be possible to derive the mechanisms triggering post-implant thromboembolic/hemorrhagic complications and to identify potential therapeutic targets.

Detailed Description
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The study is aimed at evaluating the patients' haemostatic and coagulation profile focusing, in particular, on platelet function. Platelet function will be analyzed utilizing two innovative analytic diagnostic tests, namely i) the Platelet Activity State (PAS) assay and ii) the Thrombin Generation Test (TGT). PAS values and TGT will be measured at different time-points over the course of support: i) before the implant of the support system, to define baseline patients' characteristics; ii) in the early-post implant, during patient hospitalization; iii) during long-term follow up, to evaluate the dynamics of platelet function over the course of support and potential alterations of platelet-mediated haemostatic processes; iv) at the occurrence of any thromboembolic/hemorrhagic complication or following a modification of the antithrombotic pharmacological therapy. Platelet function will be evaluated through: i) the Platelet Activity State (PAS) assay, a biochemical assay able to quantify the platelet thrombin production rate and to correlate this rate with the actual level of platelet activation (i.e., the platelet pro-thrombotic tendency); ii) the Thrombin Generation Test (TGT), a biochemical assay that the investigators have properly modified to account selectively for the platelet contribution on plasmatic thrombin generation. PAS and TGT experimental values will be correlated with the occurrences of post-implant complications. Experimental values will be also correlated with standard clinical parameters of coagulation and hemolysis, such as: platelet count, hematocrit, hemoglobin, prothrombin time (PT), activated partial thromboplastin time (aPTT), International Normalized Ratio (INR), D-Dimer, Fibrinogen, L-lactate dehydrogenase, haptoglobin, plasma-free hemoglobin, and C-reactive protein levels. Also levels of thrombin-antithrombin complex, Von Willebrand factor, prothrombin1,2 fraction and tissue factor, will be measured and recorded. In addition, pump (i.e. VAD) working parameters (i.e., rotation velocity, cardiac outflow and power consumption) will be recorded. Log-files of the pump will be downloaded and analyzed to characterize the correlation with the development of adverse events (AV). Finally, antithrombotic therapy will be recorded and used in the study.

Official Title
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Analysis of the Platelet Activity State in Patients Implanted With Ventricular Assist Device (VAD)

Conditions
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Thrombosis, Blood Coagulation Disorder, Platelet Thrombus, Platelet Dysfunction Due to Aspirin, Failure;Ventricular

Intervention / Treatment
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* Diagnostic Test: PAS assay, TGT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All consenting patients candidates for short-term (Impella, ECMO) or durable (LVAD) mechanical circulatory support device implantation All consenting patients that are implanted with short-term (Impella, ECMO) or durable (LVAD) mechanical circulatory support device Exclusion Criteria: - Patients < 18-years old

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| VAD-implanted patients<br>All patients receiving a VAD implant | Diagnostic Test: PAS assay, TGT<br>* Evaluation of platelet function<br>|
| VAD-patients suffering adverse events (AE)<br>VAD-patients sustaining a thromboembolic/bleeding complication over the course of support | Diagnostic Test: PAS assay, TGT<br>* Evaluation of platelet function<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events. Change of PAS assay from baseline to 24 months post-implant | Correlation between platelet activation and the development of post-implant complications | Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE | 
| Number of participants with treatment-related adverse events. Change of TGT from baseline to 24-months post-implant | Correlation between platelet pro-thrombinase activity and the development of post-implant complications | Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE | 
| Number of participants with treatment-related adverse events. Change of clinical and coagulation parameters from baseline to 24-months post-implant | Correlation between coagulation parameters and the development of post-implant complications | Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE | 
| Number of participants with treatment-related adverse events. Change of pump working conditions after the device implant | Correlation between pump working conditions and the development of post-implant complications | Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events. Change of prescribed antithrombotic therapy (anticoagulation and antiplatelet drugs) from baseline to 24 months post-implant | Correlation between antithrombotic therapy and the development of post-implant complications | Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombosis, Platelet activation, Ventricular Assist Device, Bleeding, Antithrombotic Pharmacological Therapy, Mechanical Circulatory Support