title: Longitudinal changes in hemostatic parameters and reduced pulsatility contribute to non-surgical bleeding in patients with centrifugal continuous-flow left ventricular assist devices.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Muthiah
authors.affiliation: Department of Haematology, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Connor
authors.affiliation: Department of Haematology, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Ly
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Gardiner
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Andrews
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia;
authors.forename: Darren
authors.initials: D
authors.lastname: Rutgers
authors.affiliation: Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia;
authors.forename: Desiree
authors.initials: D
authors.lastname: Robson
authors.affiliation: Department of Haematology, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Joyce
authors.initials: J
authors.lastname: Low
authors.affiliation: Department of Haematology, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Jarvis
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Macdonald
authors.affiliation: 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.
authors.forename: Kumud
authors.initials: K
authors.lastname: Dhital
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Jansz
authors.affiliation: 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.
authors.forename: Joanne
authors.initials: J
authors.lastname: Joseph
authors.affiliation: 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.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hayward
mesh_terms: D006353:Heart-Assist Devices; D006470:Hemorrhage; D006490:Hemostatics; D006801:Humans; D011446:Prospective Studies; D014842:von Willebrand Diseases; D014841:von Willebrand Factor
chemical_list: D006490:Hemostatics; D014841:von Willebrand Factor
keywords: acquired von Willebrand syndrome; bleeding; continuous flow; hemostatic biomarkers; left ventricular assist device