Longitudinal changes in hemostatic parameters and reduced pulsatility contribute to non-surgical bleeding in patients with centrifugal continuous-flow left ventricular assist devices

Kavitha Muthiah; David Connor; Ken Ly; Elizabeth E Gardiner; Robert K Andrews; Jianlin Qiao; Darren Rutgers; Desiree Robson; Joyce Low; Susan Jarvis; Peter Macdonald; Kumud Dhital; Paul Jansz; Joanne Joseph; Christopher S Hayward

doi:10.1016/j.healun.2015.12.024

Longitudinal changes in hemostatic parameters and reduced pulsatility contribute to non-surgical bleeding in patients with centrifugal continuous-flow left ventricular assist devices

J Heart Lung Transplant. 2016 Jun;35(6):743-51. doi: 10.1016/j.healun.2015.12.024. Epub 2016 Jan 7.

Authors

Affiliations

¹ Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia;; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
² Department of Haematology, St. Vincent's Hospital, Sydney, New South Wales, Australia.
³ Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
⁴ Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia;
⁵ Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia;; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁶ Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; Department of Haematology, St. Vincent's Hospital, Sydney, New South Wales, Australia.
⁷ Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia;; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia. Electronic address: cshayward@stvincents.com.au.

PMID: 26987598
DOI: 10.1016/j.healun.2015.12.024

Abstract

Background: Bleeding and thromboembolic events are identified complications in patients supported with newer centrifugal continuous-flow left ventricular assist devices (cfLVADs). Bleeding events have been associated with acquired von Willebrand syndrome (vWS) in these patients, though longitudinal changes and the effect of pulsatility remain unquantified. We evaluated longitudinal effects of third-generation cfLVADs on hemostatic biomarkers, non-surgical bleeding, and thromboembolic events. We investigated the association between pulsatility (as defined by aortic valve opening) on von Willebrand Factor (VWF) profile and bleeding.

Methods: We prospectively studied 28 patients implanted with the HeartWare (HeartWare International, Framingham, MA) cfLVAD for up to 360 days. We performed bleeding and coagulation assays 8 times from pre-implant to Day 360 (D360) post-implant, including platelet aggregometry, VWF collagen binding activity-to-antigen (CBA/Ag) ratio, thromboelastography, soluble P-selectin, platelet-specific marker soluble glycoprotein VI (sGPVI), and platelet microparticles. Aortic valve opening was assessed by echocardiography at each assessment. Bleeding and thromboembolic events were documented.

Results: Bleeding events occurred in 14 patients (50%). Maximal platelet inhibition occurred by D30. VWF profile impairment (VWF CBA/Ag < 0.8) was demonstrated in 89% of patients at D30, with subsequent recovery but further deterioration after D180. Bleeding was associated with elevated pre-implant sGPVI (p = 0.008). Pulsatility was associated with higher VWF CBA/Ag (p = 0.02) and a trend to less bleeding.

Conclusions: Third-generation cfLVADs were associated with longitudinal changes in hemostatic markers, and bleeding was associated with elevated pre-implant plasma sGPVI. Further, pulsatility may contribute to recovery of the VWF profile and potentially lower bleeding risk.

Keywords: acquired von Willebrand syndrome; bleeding; continuous flow; hemostatic biomarkers; left ventricular assist device.

MeSH terms

Heart-Assist Devices
Hemorrhage*
Hemostatics
Humans
Prospective Studies
von Willebrand Diseases
von Willebrand Factor

Substances

Hemostatics
von Willebrand Factor