Platelet Function and Impella Support (IMPELLA-PLT)

Università Vita-Salute San Raffaele

Status

Enrolling

Conditions

Cardiogenic Shock

Cardiac Arrest

Mechanical Circulatory Support

Treatments

Diagnostic Test: Analysis of platelet function

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT06487091

IMPELLA-PLT

Details and patient eligibility

About

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.

Full description

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.

Data will be measured

pre-implant (i.e., immediately prior to Impella implantation), to evaluate the patient-specific baseline profile, and then following
24 hours, 48 hours, and 72 hours of Impella support. This way it will possible to quantify longitudinal changes in the levels of expression of the selected markers over the course of Impella support (vs. baseline).

Data will be also measured during the acute phase of any of the following adverse events that will occur during Impella support (not limited to 72 hours):

thrombosis (of the patient - any site - and of the pump)
ischemic/hemorrhagic stroke
any surgical or non-surgical bleeding
hemolysis Adverse events will be defined according to most recent criteria [6-8].

Furthermore, inferences of any change in the anticaogulation regimen that may occur over the course of Impella support (not limited to 72 hours) will be evaluated: to this aim, markers of platelet function will be analyzed 12 hours following any change in the anticoagulation regimen.

Experimental data will be correlated with clinical outcomes, including the occurrence of adverse events, to possibly identify an "event-related platelet function profile" characteristics of the sub-group of patients that will develop adverse events. The occurrence of adverse events will be continuously recorded over the whole duration of Impella support.

TREATMENT PROCEDURE To measure the expression levels of the selected markers of platelet function, platelet samples will be isolated from patients' blood (10-mL volume) via standard laboratory techniques. The expression levels of the analyzed markers will be measured via quantitative real-time polymerase chain reaction and protein quantitation/function assay, such as enzyme-linked immunosorbent assay.

Enrollment

30 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria