Insights into the mechanism(s) of von Willebrand factor degradation during mechanical circulatory support

Carlo R. Bartoli, Sujith Dassanayaka, Kenneth R. Brittian, Andrew Luckett, Srinivas Sithu, Thorsten Siess, Daniel H. Raess, Paul A. Spence, Steven C. Koenig, Robert Dowling, Stanley E. D'Souza

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Abstract

Objective: Left ventricular assist device support produces a bleeding diathesis. Evidence suggests a major role for von Willebrand factor (vWF). We examined vWF metabolism in a preclinical model of short-term mechanical circulatory support. Methods: In 25 calves (weight, 80-110 kg), the inflow/outflow graft of the Symphony Heart Assist System was sewn end-to-side to the carotid artery. Support was initiated (acute, n = 4; 1 week, n = 16; 2 weeks, n = 5). Acutely, carotid artery pressure and flow were measured to evaluate the hemodynamic changes near the anastomosis. At baseline and after ≤2 weeks of support, platelet aggregometry with adenosine 5′-diphosphate, collagen, and ristocetin was performed. Gel electrophoresis and wet immunoblotting qualitatively evaluated vWF multimers and quantified plasma ADAMTS-13, the vWF-cleaving protease. Carotid arterial rings near the anastomosis were studied with immunohistochemical staining for ADAMTS-13 and were cultured to quantify endothelial ADAMTS-13 production. Fluorescent resonance energy transfer was used to evaluate the enzymatic activity of ADAMTS-13 in the plasma and in supernatant from cultured carotid arterial rings. Plasma interleukin-6, which inhibits ADAMTS-13 activity, was measured using an enzyme-linked immunosorbent assay. Results: During support, statistically significant (P <.05) changes in the carotid endothelium arterial hemodynamics were observed. The highest molecular weight vWF multimers were absent, and the vWF-ristocetin platelet aggregation pathway was significantly impaired. A modest but significant increase in plasma ADAMTS-13 protein and activity was observed. ADAMTS-13 decreased significantly in the carotid near the anastomosis but increased significantly in supernatant from cultured carotid arterial rings. The plasma interleukin-6 levels did not change significantly. Conclusions: Hemodynamic activation of vWF and increased plasma ADAMTS-13 activity may have reduced high-molecular-weight vWF multimers and thereby impaired the vWF-platelet aggregation pathway. Additional delineation of these pathways may improve management of left ventricular assist device-Associated bleeding.

Original languageEnglish (US)
Pages (from-to)1634-1643
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Volume147
Issue number5
DOIs
Publication statusPublished - Jan 1 2014

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All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Bartoli, C. R., Dassanayaka, S., Brittian, K. R., Luckett, A., Sithu, S., Siess, T., ... D'Souza, S. E. (2014). Insights into the mechanism(s) of von Willebrand factor degradation during mechanical circulatory support. Journal of Thoracic and Cardiovascular Surgery, 147(5), 1634-1643. https://doi.org/10.1016/j.jtcvs.2013.08.043