Analysis of Platelet Function During Impella Support
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Expression levels of platelet surface markers of activation and aggregation and platelet microRNAs in patients on Impella support
研究概览
简要总结
Mechanical circulatory support (MCS) with the Impella microaxial pump in the setting of cardiogenic shock/cardiac arrest (CS/CA) is accompanied by substantial risk of life-threatening complications, including hemolysis, thrombotic and bleeding events.
Previous studies in patients on durable MCS suggest that device-induced platelet dysfunction plays a major contributory role in the development of such events and that selected markers of platelet function have the potential to stratify patients according to an elevated risk of adverse events. To date, the potential clinical utility of markers of altered platelet function in patients supported with an Impella pump is unexplored.
The proposed study will analyze changes in platelet function in the setting of Impella support (primary aim) and possibly identify a platelet function "profile" indicative of patients at high-risk to develop adverse events (secondary aim).
The study is a prospective observational study. Changes in the expression levels of markers of both platelet activation and aggregation in patients supported with an Impella pump will be measured. Data will be longitudinally measured: pre-implant (before Impella implantation) and then after 24, 48 and 72h of Impella support. Markers that will be analyzed include surface platelet receptors and platelet microRNAs. Experimental data will be correlated with clinical outcomes, including the occurrence of adverse events.
This study will provide mechanistic insights into the effect of Impella support on the protein and miRNA expression of platelets. The intention is to get a better understanding of distinct pathways of platelet function related to Impella support and their relationship to adverse events. Our data might open the perspective for the future clinical use of markers of platelet function to enhance the early recognition of patients at high risk of developing an adverse event and the definition of novel, personalized therapeutic strategies targeted to platelet biology to prevent their occurrence.
详细描述
STUDY DESIGN AND MAIN OBJECTIVE Prospective observational study to evaluate changes in the expression levels of markers of platelet function (activation and aggregation capacity) in CS/CA patients who receive an Impella device for temporary mechanical circulatory support
HYPOTHESIS
- progressive change of platelet function occurs over the course of Impella support driven by shear forces exerted by the pump on recirculating blood
- markers of changes in platelet function can be identified at the protein and nuclear level in platelet samples extracted form patients supported with an Impella pump
- specific trends of the changes of the expression levels of markers of platelet function might allow identifying patients at higher risk of developing a thrombotic/hemorrhagic complication
- the expression levels of markers of platelet function are indeed altered in patients even before the clinical manifestation of the event
METHODOLOGY The markers that will be analyzed have been selected according to recent studies showing
- significant changes in their expression levels driven by durable MCS devices
- their potential to identify patients at high risk of developing adverse events
- their association with coagulation/hemostatic disorders and hemolysis and include:
- platelet receptors GPIba, GPIIb/IIIa, and GPVI [1-4].
- platelet microRNA miR-20b-5p, miR-25-3p, miR-126-5p, miR-451a, miR-320a, miR-223-3p, miR-144-rp, miR-151a-3p, and miR-454-3p [5]. The expression levels of these microRNAs will be measured in both PRP and PPP samples, to confirm their actual expression by platelets.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients >18yrs-old and <75yrs-old
- •Cardiogenic shock SCAI class C-D-E
- •primary tMCS with an Impella device (all Impella pumps)
- •Informed consent
排除标准
- •Patients <18yrs-old or >75yrs-old
- •Refusal to participate to the study
结局指标
主要结局
Expression levels of platelet surface markers of activation and aggregation and platelet microRNAs in patients on Impella support
时间窗: baseline (prior to Impella implantation) vs. 24 hours, 48 hours and 72 hours of Impella support
Changes (measured as percentage variation) in the expression levels of platelet surface markers of activation and aggregation (GPIba, GPIIb/IIIa, and GPVI) and platelet microRNA (miR-20b-5p, miR-25-3p, miR-126-5p, miR-451a, miR-320a, miR-223-3p, miR-144-rp, miR-151a-3p, and miR-454-3p) during tMCS with an Impella device (all Impella pumps)
次要结局
- Expression levels of platelet surface markers of activation and aggregation and platelet microRNAs in the acute phase of an adverse event (hemolysis, thrombosis, bleeding). Adverse events will be determined according to [6-8](immediately after any adverse event, anticipated average 30 days)
- Expression levels of platelet surface markers of activation and aggregation and platelet microRNAs after any change in the antithrombotic regimen(12 hours after any change in the antithrombotic regimen)
研究者
Filippo Consolo
Assistant Professor
IRCCS Ospedale San Raffaele