Acquired von Willebrand Syndrome in Continuous-Flow Ventricular Assist Device Recipients

Abstract

Consistent survival benefits and reduced adverse events have established the left ventricular assist device (LVAD) as a valuable tool in the management of congestive heart failure. However, bleeding complications unrelated to the implant procedure are a major cause of morbidity and mortality in recipients of continuous-flow left ventricular assist devices (CF-LVAD) [ 1 x 1 John, R., Kamdar, F., Liao, K. et al. Improved survival and decreasing incidence of adverse events with the HeartMate left ventricular assist device as bridge-to-transplant therapy. Ann Thorac Surg. 2008; 86: 1227–1235 Abstract | Full Text | Full Text PDF | PubMed | Scopus (196) | Google Scholar See all References 1 ]. Two recent reviews of CF-LVAD recipients demonstrated bleeding event rates as high as 65% within the first year after LVAD placement [ 2 x 2 Slaughter, M.S., Rogers, J.G., Milano, C.A. et al. Advanced heart failure treated with continuous flow left ventricular assist device. N Engl J Med. 2009; 361: 2241–2251 Crossref | PubMed | Scopus (1678) | Google Scholar See all References , 3 x 3 Crow, S., John, R., Boyle, A. et al. Gastrointestinal bleeding rates in recipients of continuous flow and pulsatile left ventricular assist devices. J Thorac Cardiovasc Surg. 2009; 137: 208–215 Abstract | Full Text | Full Text PDF | PubMed | Scopus (266) | Google Scholar See all References ]. The majority of these events appear to be gastrointestinal (GI) or nasal mucosal bleeds. This bleeding pattern is very similar to that observed in patients with aortic stenosis and secondary acquired von Willebrand syndrome (AVWS) [ 4 x 4 Pedrotty DM, Welsby I, Daneshmand MA, et al. Bleeding and thromboembolic complications with the HeartMate XVE and HeartMate II. Paper presented at the 29th Annual Meeting of the International Society for Heart and Lung Transplantation, April 22–25, 2009, Paris, France. Google Scholar See all References , 5 x 5 Warkentin, T.E., Moore, J.C., and Morgan, D.G. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link?. Lancet. 1992; 340: 35–37 Abstract | PubMed | Scopus (194) | Google Scholar See all References ]. In aortic stenosis, proteolytic cleavage or accelerated clearance of high molecular weight (HMW) von Willebrand factor (vWF) multimers are believed to occur after conformational changes in vWF. These changes are induced by the high shear across the calcific aortic valve. The result is a reduction in HMW vWF multimers believed to be essential for promoting platelet adhesion in high shear stress areas such as GI arteriovenous malformations [ 6 x 6 Vincentelli, A., Susen, S., Le Tourneau, T. et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003; 349: 343–349 Crossref | PubMed | Scopus (466) | Google Scholar See all References , 7 x 7 Veyradier, A., Balian, A., Wolf, M. et al. Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract. Gastroenterology. 2001; 120: 346–353 Abstract | Full Text | Full Text PDF | PubMed | Scopus (118) | Google Scholar See all References , 8 x 8 Lopez, J.A. and Dong, J. Shear stress and the role of high molecular weight von Willebrand factor multimers in thrombus formation. Blood Coag Fibrinol. 2005; 16: 11–16 Crossref | Google Scholar See all References ].