Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices

Lorenzo Valerio, Phat L. Tran, Jawaad Sheriff, William Brengle, Ram Ghosh, Wei Che Chiu, Alberto Redaelli, Gianfranco B. Fiore, Federico Pappalardo, Danny Bluestein, Marvin J. Slepian

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Continuous flow ventricular assist devices (cfVADs) while effective in advanced heart failure, remain plagued by thrombosis related to abnormal flows and elevated shear stress. To limit cfVAD thrombosis, patients utilize complex anti-thrombotic regimens built upon a foundation of aspirin (ASA). While much data exists on ASA as a modulator of biochemically-mediated platelet activation, limited data exists as to the efficacy of ASA as a means of limiting shear-mediated platelet activation, particularly under elevated shear stress common within cfVADs. We investigated the ability of ASA (20, 25 and 125 μM) to limit shear-mediated platelet activation under conditions of: 1) constant shear stress (30 dynes/cm2 and 70 dynes/cm2); 2) dynamic shear stress, and 3) initial high shear exposure (70 dynes/cm2) followed by low shear exposure-i.e. a platelet sensitization protocol, utilizing a hemodynamic shearing device providing uniform shear stress in vitro. The efficacy of ASA to limit platelet activation mediated via passage through a clinical cfVAD system (DeBakey Micromed) in vitro was also studied. ASA reduced platelet activation only under conditions of low shear stress (38% reduction compared to control, n = 10, p <0.004), with minimal protection at higher shear stress and under dynamic conditions (n = 10, p > 0.5) with no limitation of platelet sensitization. ASA had limited ability (25.6% reduction in platelet activation rate) to modulate shear-mediated platelet activation induced via cfVAD passage. These findings, while performed under "deconstructed" non-clinical conditions by utilizing purified platelets alone in vitro, provide a potential contributory mechanistic explanation for the persistent thrombosis rates experienced clinically in cfVAD patients despite ASA therapy. An opportunity exists to develop enhanced pharmacologic strategies to limit shear-mediated platelet activation at elevated shear levels associated with mechanical circulatory support devices.

Original languageEnglish
Pages (from-to)110-117
Number of pages8
JournalThrombosis Research
Volume140
DOIs
Publication statusPublished - Apr 1 2016

Fingerprint

Heart-Assist Devices
Platelet Activation
Aspirin
Thrombosis
Blood Platelets
Equipment and Supplies
Heart Failure
Hemodynamics

Keywords

  • Aspirin
  • Mechanical circulatory support
  • Platelets
  • Shear
  • Thrombosis
  • Ventricular assist devices

ASJC Scopus subject areas

  • Hematology

Cite this

Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices. / Valerio, Lorenzo; Tran, Phat L.; Sheriff, Jawaad; Brengle, William; Ghosh, Ram; Chiu, Wei Che; Redaelli, Alberto; Fiore, Gianfranco B.; Pappalardo, Federico; Bluestein, Danny; Slepian, Marvin J.

In: Thrombosis Research, Vol. 140, 01.04.2016, p. 110-117.

Research output: Contribution to journalArticle

Valerio, L, Tran, PL, Sheriff, J, Brengle, W, Ghosh, R, Chiu, WC, Redaelli, A, Fiore, GB, Pappalardo, F, Bluestein, D & Slepian, MJ 2016, 'Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices', Thrombosis Research, vol. 140, pp. 110-117. https://doi.org/10.1016/j.thromres.2016.01.026
Valerio, Lorenzo ; Tran, Phat L. ; Sheriff, Jawaad ; Brengle, William ; Ghosh, Ram ; Chiu, Wei Che ; Redaelli, Alberto ; Fiore, Gianfranco B. ; Pappalardo, Federico ; Bluestein, Danny ; Slepian, Marvin J. / Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices. In: Thrombosis Research. 2016 ; Vol. 140. pp. 110-117.
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AU - Ghosh, Ram

AU - Chiu, Wei Che

AU - Redaelli, Alberto

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