Comparative Analysis of von Willebrand Factor Profiles in Pulsatile and Continuous Left Ventricular Assist Device Recipients

Abstract

A higher rate of nonsurgical bleeding has been observed in nonpulsatile left ventricular assist device (LVAD) recipients. von Willebrand factor (vWF) profiles were compared for nonpulsatile and pulsatile LVAD recipients to explore mechanisms that may contribute to the development of postimplant nonsurgical bleeding. The nonpulsatile mechanism may impair vWF function by creating a deficiency in vWF high molecular weight multimers (HMWMs), essential for hemostasis. High molecular weight multimer deficiency should result in low ristocetin cofactor (RCo) to vWF antigen ratios (vWF:RCo/vWF:Ag) because of impaired platelet (plt)-binding ability. von Willebrand factor profiles and HMWM were measured pre- and post-LVAD placement in 11 nonpulsatile (HeartMate II [HM II[) and 3 pulsatile (HeartMate XVE [HM XVE]) recipients. All the nonpulsatile LVAD recipients exhibited loss of HMWM 30 days postimplant. The vWF:RCo/vWF:Ag ratio was significantly lower after LVAD placement in the nonpulsatile group when compared with the pulsatile group. In addition, the vWF:RCo/vWF:Ag ratio decreased significantly from baseline 30 days postimplant within the nonpulsatile recipients. All nonpulsatile LVAD recipients had low vWF:RCo/vWF:Ag ratios 30 days post-LVAD even if the values were normal at baseline. These data suggest that nonpulsatile HM II recipients develop HMWM loss and impaired vWF platelet (plt)-binding ability after LVAD placement. Similar results were not observed in our small series of pulsatile HM XVE recipients. This finding could suggest a contributing factor to the increase in nonsurgical bleeding observed in nonpulsatile LVAD patients. Further investigation is ongoing to identify specific causes of vWF impairment.

Pulsatility and the Risk of Nonsurgical Bleeding in Patients Supported With the Continuous-Flow Left Ventricular Assist Device HeartMate II

“…In addition, bleeding events occurred even in the absence of supratherapeutic anticoagulation, 30,32 a fact also seen in our study where 82% of the patients with bleeding had an INR within the desired therapeutic range. Other factors have been implicated in the increased incidence of bleeding in CF-LVADs, including the development of acquired von Willebrand syndrome, 14,16,17,33,34 impairment in platelet aggregation, 15 and the lack of pulsatility. The potential role of the first 2 factors in the bleeding diathesis observed in patients with CF-LVADs has been investigated; however, the role of pulsatility in this setting is less clear.…”

Pilot investigation of a novel testing strategy for bleeding in ventricular assist device recipients

“…4 We previously reported a universal loss of the HMWM in continuous-flow LVAD recipients. 5 This abnormality may be associated with an increased bleeding risk during the peri-operative and post-operative device support period. Bleeding complications, when present, often require a modification in anticoagulation strategy for some patients.…”

Mechanisms of Bleeding and Approach to Patients With Axial-Flow Left Ventricular Assist Devices

“…As the shear stress rate increases, the molecule is prone to unfolding, resulting in greater cleavage rates and smaller vWF multimers. 27 Multiple studies 16,17,28 have shown that most patients who undergo implantation with an axial-flow LVAD will develop some degree of acquired von Willebrand disease. In a retrospective review 16 of 79 patients with a HeartMate II LVAD, all patients had decreased or absent HMW vWF multimers that normalized after heart transplantation.…”