title: Hemolysate-mediated platelet aggregation: an additional risk mechanism contributing to thrombosis of continuous flow ventricular assist devices.
abstract: Despite the clinical success and growth in the utilization of continuous flow ventricular assist devices (cfVADs) for the treatment of advanced heart failure, hemolysis and thrombosis remain major limitations. Inadequate and/or ineffective anticoagulation regimens, combined with high pump speed and non-physiological flow patterns, can result in hemolysis which often is accompanied by pump thrombosis. An unexpected increase in cfVADs thrombosis was reported by multiple major VAD implanting centers in 2014, highlighting the association of hemolysis and a rise in lactate dehydrogenase (LDH) presaging thrombotic events. It is well established that thrombotic complications arise from the abnormal shear stresses generated by cfVADs. What remains unknown is the link between cfVAD-associated hemolysis and pump thrombosis. Can hemolysis of red blood cells (RBCs) contribute to platelet aggregation, thereby, facilitating prothrombotic complications in cfVADs? Herein, we examine the effect of RBC-hemolysate and selected major constituents, i.e., lactate dehydrogenase (LDH) and plasma free hemoglobin (pHb) on platelet aggregation, utilizing electrical resistance aggregometry. Our hypothesis is that elements of RBCs, released as a result of shear-mediated hemolysis, will contribute to platelet aggregation. We show that RBC hemolysate and pHb, but not LDH, are direct contributors to platelet aggregation, posing an additional risk mechanism for cfVAD thrombosis.
authors.affiliation: University of Arizona, Tucson, AZ, USA.
authors.forename: Phat L
authors.initials: PL
authors.lastname: Tran
authors.affiliation: Politecnico di Milano, Milano, Italy.
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Pietropaolo
authors.affiliation: Politecnico di Milano, Milano, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Valerio
authors.affiliation: University of Arizona, Tucson, AZ, USA.
authors.forename: William
authors.initials: W
authors.lastname: Brengle
authors.affiliation: University of Arizona, Tucson, AZ, USA.
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Wong
authors.affiliation: University of Arizona, Tucson, AZ, USA.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Kazui
authors.affiliation: University of Arizona, Tucson, AZ, USA.
authors.forename: Zain I
authors.initials: ZI
authors.lastname: Khalpey
authors.affiliation: Politecnico di Milano, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Redaelli
authors.affiliation: Stony Brook University, Stony Brook, NY, USA.
authors.forename: Jawaad
authors.initials: J
authors.lastname: Sheriff
authors.affiliation: Stony Brook University, Stony Brook, NY, USA.
authors.forename: Danny
authors.initials: D
authors.lastname: Bluestein
authors.affiliation: University of Arizona, Tucson, AZ, USA Stony Brook University, Stony Brook, NY, USA chairman.syns@gmail.com.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Slepian
mesh_terms: D006333:Heart Failure; D006353:Heart-Assist Devices; D006461:Hemolysis; D006801:Humans; D010974:Platelet Aggregation; D000091402:Prohibitins; D013927:Thrombosis / Q000188:drug therapy
keywords: hemolysis; lactate dehydrogenase (LDH); multiplate analyzer; platelet aggregation; thrombosis; ventricular assist devices