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Prospective, observational study of antiplatelet and coagulation biomarkers as predictors of thromboembolic events after implantation of ventricular assist devices

Nature Clinical Practice Cardiovascular Medicine volume 6, pages 147–157 (2009)Cite this article

Abstract

Background Long-term success in ventricular assist device (VAD) recipients is limited by thromboembolic events, the prediction of which remains elusive. We evaluated the predictive value of aspirin hyporesponsiveness and markers of coagulation and fibrinolysis.

Methods We prospectively enrolled patients scheduled to undergo VAD implantation between June 2004 and March 2006. Once before surgery, daily during hospitalization, and weekly after discharge we assessed platelet function, measured prothrombin activation fragment 1.2 (F1.2) and plasminogen activator inhibitor-1 (PAI-1) concentrations, and evaluated aspirin hyporesponsiveness by whole-blood aggregometry and thromboelastography. All patients received 325 mg oral aspirin daily from at least 7 days before VAD implantation. Follow-up continued until heart transplantation, death or closure of the database.

Results We included 26 patients (median follow-up 315 days, range 9–833 days). In eight (31%) patients, 14 thromboembolic events occurred at a median of 42 (interquartile range 26–131) days. Only six (43%) events based on whole-blood aggregometry and one (7%) based on thromboelastography coincided with aspirin hyporesponsiveness. Within-patient variability was high for both tests (59% and 567%, respectively). Compared with levels before surgery, PAI-1 concentrations were raised for up to 45 days (P <0.0001) and those of F1.2 for up to 3 days (P = 0.0001) after VAD implantation. PAI-1 and F1.2 levels did not rise significantly further before thromboembolic events.

Conclusions Aspirin hyporesponsiveness was not associated with raised risk of future clinical thromboembolic events after VAD implantation. Impaired fibrinolysis, demonstrated by raised PAI-1 concentrations, might, however, indicate a predisposition to such events early after surgery.

Key Points

  • Biological aspirin hyporesponsiveness is common in patients with end-stage systolic heart failure before and after implantation of ventricular assist devices

  • Thromboembolic events occur at a high rate—nearly one-third—in patients with ventricular assist devices

  • No significant association was observed between the presence of aspirin hyporesponsiveness, based on whole-blood aggregometry and thromboelastography assays, and thromboembolic events in patients with ventricular assist devices

  • Plasminogen activator inhibitor-1 values early after ventricular assist device implantation suggest impaired fibrinolysis predisposes patients to thromboembolic events

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Figure 1: Changes in platelet aggregation activity in patients experiencing thromboembolic events.
Figure 2: Variability of whole-blood aggregometry values in eight patients with thromboembolic events.
Figure 3: Levels of PAI-1 in relation to VAD placement and incidence of thromboembolic events during follow-up.

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Authors and Affiliations

  1. Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD, USA

    Farhan Majeed, Willem J Kop & Mandeep R Mehra

  2. Division of Cardiothoracic Surgery, Boston Medical Center, Boston University, Boston, MA, USA

    Robert S Poston & Seeta Kallam

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  1. Farhan Majeed
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Correspondence to Mandeep R Mehra.

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Competing interests

F Majeed, WJ Kop, RS Poston and S Kallam declared no competing interests.

MR Mehra has served as a consultant to Ventracor and Thoratec with regard to their mechanical circulatory assist devices.

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Majeed, F., Kop, W., Poston, R. et al. Prospective, observational study of antiplatelet and coagulation biomarkers as predictors of thromboembolic events after implantation of ventricular assist devices. Nat Rev Cardiol 6, 147–157 (2009). https://doi.org/10.1038/ncpcardio1441

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