Left ventricular assist device implantation causes platelet dysfunction and proinflammatory platelet-neutrophil interaction

Abstract

Blood flow through left ventricular assist devices (LVAD) may induce activation and dysfunction of platelets. Dysfunctional platelets cause coagulation disturbances and form platelet-neutrophil conjugates (PNC), which contribute to inflammatory tissue damage. This prospective observational cohort study investigated patients, who underwent implantation of a LVAD (either HeartMate II (HM II) (n = 7) or HeartMate 3 (HM 3) (n = 6)) and as control patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) (n = 10). We performed platelet and leukocyte flow cytometry, analysis of platelet activation markers, and platelet aggregometry. Platelet CD42b expression was reduced at baseline and perioperatively in HM II/3 compared to CABG/AVR patients. After surgery the platelet activation marker β-thromboglobulin and platelet microparticles increased in all groups while platelet aggregation decreased. Platelet aggregation was more significantly impaired in LVAD compared to CABG/AVR patients. PNC were higher in HM II compared to HM 3 patients. We conclude that LVAD implantation is associated with platelet dysfunction and proinflammatory platelet-leukocyte binding. These changes are less pronounced in patients treated with the newer generation LVAD HM 3. Future research should identify device-specific LVAD features, which are associated with the least amount of platelet activation to further improve LVAD therapy.

Keywords:

• Left ventricular assist device
• mechanical circulatory support
• platelet dysfunction
• platelet-leukocyte interaction
• systemic inflammation

Acknowledgements

We thank Julia Krieg (Dept. of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, Germany) for her technical contribution to analyzing beta-TG and PMN elastase levels.

Disclosure Of Interest

Andreas Straub has received speaker honoraria and travel support from CSL Behring GmbH (Munich, Germany) as well as speaker honoraria from Schöchl Medical Education GmbH (Mattsee, Austria) and Aspen Germany GmbH (Munich, Germany). Harry Magunia has received a speaker’s honorarium from CSL Behring GmbH (Munich, Germany). No additional conflicts of interest exist for any of the authors.

Author Contributions

These contributions follow the Contributor Roles Taxonomy guidelines: https://casrai.org/credit/. Conceptualization: D.S., H.P.W., C.S., H.H., P.R., A.S. Data curation: P.S. Formal analysis: T.G., P.S., L.S-H., A.S. Funding acquisition: P.R., A.S. Investigation: T.G., H.M., P.S., C.F., T.P., D.S., H.H., A.S., Methodology: T.G., L.S-H., H.P.W., A.S. Project administration: P.S., H.H., P.R., A.S. Supervision: C.S., H.H., P.R., A.S. Resources: H.M., C.F., T.P., H.P.W., C.S., H.H., P.R. Visualization: T.G., P.S., L.S-H. Writing – original draft: T.G., C.F., D.S., L.S-H., H.H., P.R., A.S. Writing – review & editing: T.G., H.M., P.S., L.S-H, A.S. All authors had the opportunity to read and comment on the final manuscript.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by a grant of the AKF program of the University of Tübingen (Tübingen, Germany) to Andreas Straub (grant number AKF-330-0-0) and the grant DFG CRC/TR 240 “Platelets - Molecular, cellular and systemic functions in health and disease” (Project # 374031971) TP B07 to Peter Rosenberger; AKF program of the University of Tübingen (Tübingen, Germany) [AKF-330-0-0]; DFG [CRC/TR 240 “Platelets - Molecular, cellular and sy].