Changes in von Willebrand factor-cleaving protease (ADAMTS-13) in patients with aortic stenosis undergoing valve replacement or balloon valvuloplasty

Jeffrey Bander; Sammy Elmariah; Louis M. Aledort; Jeffrey Dlott; Paul Stelzer; Jonathan L. Halperin; Annapoorna S. Kini; Samin K. Sharma

doi:10.1160/TH11-12-0803

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 108(01): 86-93
DOI: 10.1160/TH11-12-0803

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Changes in von Willebrand factor-cleaving protease (ADAMTS-13) in patients with aortic stenosis undergoing valve replacement or balloon valvuloplasty

Jeffrey Bander^*

¹Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York, USA

,

Sammy Elmariah^*

¹Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York, USA

²Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

,

Louis M. Aledort

³Department of Medicine – Hematology, The Mount Sinai School of Medicine, New York, New York, USA

,

Jeffrey Dlott

⁴Quest Diagnostics Nichols Institute, Chantilly, Virginia; USA

,

Paul Stelzer

¹Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York, USA

,

Jonathan L. Halperin

¹Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York, USA

,

Annapoorna S. Kini

¹Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York, USA

,

Samin K. Sharma

¹Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York, USA

› Author Affiliations

Abstract

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Summary

It was the objective of this study to determine whether reduced cleavage of von Willebrand factor (VWF) multimers following aortic valve replacement (AVR) is a consequence of reduced shear stress or postoperative changes in VWF cleavage protease (ADAMTS-13) activity. Aortic stenosis (AS) may be complicated by acquired von Willebrand disease. Aortic valve replacement (AVR) corrects the associated haematologic abnormalities. We enrolled 114 patients with severe AS scheduled for either balloon aortic valvuloplasty (BAV; n=64) or AVR (n=50). Haematologic assessments of VWF levels and activity and ADAMTS-13 were performed before and 24 hours after valve intervention. The VWF:RCo to VWF:Ag ratio, a surrogate for large VWF multimer activity, increased by 37% (p < 0.0001) after AVR and by 10% (p = 0.0002) after BAV. ADAMTS-13 activity significantly decreased after AVR (579 ± 127 to 468 ± 135 ng/ml; p<0.0001), but not after BAV (484 ± 153 to 529 ± 185 ng/ml; p = 0.10). By multivariable analysis, the change in VWF:RCo ratio after AVR was more strongly associated with the fall in ADAMTS-13 than with reduction of valve gradient; whereas the change in gradient better predicted the rise in VWF:RCo after BAV. In conclusion, both BAV and AVR reverse the haematological abnormalities of the acquired von Willebrand syndrome of AS and ADAMTS-13 levels decrease after AVR. These findings suggest that a portion of the haematologic benefit of AVR may be due to a postoperative decline in ADAMTS-13 rather than solely to relief of AS as previously thought.

Keywords

Acquired coagulation disorders - ADAMTS-13 - aortic valve stenosis - balloon aortic valvuloplasty - von Willebrand factor

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References

References
1 Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link?. Lancet 1992; 340: 35-37.
2 Gill JC, Wilson AD, Endres-Brooks J. et al. Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood 1986; 67: 758-761.
3 Weinstein M, Ware JA, Troll J. et al. Changes in von Willebrand factor during cardiac surgery: effect of desmopressin acetate. Blood 1988; 71: 1648-1655.
4 Undas A, Windyga J, Bykowska K. et al. Heyde's syndrome without a decrease in large von Willebrand factor multimers: a case of intestinal bleedings reversed by valve replacement in a patient with aortic stenosis. Thromb Haemost 2009; 101: 773-774.
5 Casonato A, Sponga S, Pontara E. et al. von Willebrand factor abnormalities in aortic valve stenosis: Pathophysiology and impact on bleeding. Thromb Haemost 2011; 106: 58-66.
6 Warkentin TE, Moore JC. Heyde's syndrome: From controversy to mainstream. Thromb Haemost 2010; 103: 251-253.
7 Panzer S, Badr-Eslam R, Schneller A. et al. Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis. Thromb Haemost 2010; 103: 408-414.
8 Vincentelli A, Susen S, Le Tourneau T. et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349: 343-349.
9 Pareti FI, Lattuada A, Bressi C. et al. Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation 2000; 102: 1290-1295.
10 Tsai HM. Shear stress and von Willebrand factor in health and disease. Semin Thromb Hemost 2003; 29: 479-488.
11 Dent JA, Berkowitz SD, Ware J. et al. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Wille-brand factor. Proc Natl Acad Sci USA 1990; 87: 6306-6310.
12 Zhang X, Halvorsen K, Zhang CZ. et al. Mechanoenzymatic cleavage of the ultra-large vascular protein von Willebrand factor. Science 2009; 324: 1330-1334.
13 Steinl e c, hner B, Zeidler P, Base E. etal Patients with severe aortic valve stenosis and impaired platelet function benefit from preoperative desmopressin infusion. Ann Thorac Surg 2011; 91: 1420-1426.
14 Yoshida K, Tobe S, Kawata M. et al. Acquired and reversible von Willebrand disease with high shear stress aortic valve stenosis. Ann Thorac Surg 2006; 81: 490-494.
15 Feys HB, Deckmyn H, Vanhoorelbeke K. ADAMTS13 in health and disease. Acta Haematol 2009; 121: 183-185.
16 Reiter RA, Knobl P, Varadi K. et al. Changes in von Willebrand factor-cleaving protease (ADAMTS13) activity after infusion of desmopressin. Blood 2003; 101: 946-948.
17 Reiter RA, Varadi K, Turecek PL. et al. Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammation. Thromb Haemost 2005; 93: 554-558.
18 van den Born BJ, van der Hoeven NV, Groot E. et al. Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension. Hypertension 2008; 51: 862-866.
19 Zhou Z, Han H, Cruz MA. et al. Haemoglobin blocks von Willebrand factor proteolysis by ADAMTS-13: a mechanism associated with sickle cell disease. Thromb Haemost 2009; 101: 1070-1077.
20 Mannucci PM, Parolari A, Canciani MT. et al. Opposite changes of ADAMTS-13 and von Willebrand factor after cardiac surgery. J Thromb Haemost 2005; 03: 397-399.
21 Lo B, Nierich AP, Kalkman CJ. et al. Relatively increased von Willebrand factor activity after off-pump coronary artery bypass graft surgery. Thromb Haemost 2007; 97: 21-26.
22 Bonow RO, Carabello BA, Chatterjee K. et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008; 118: e523-661.
23 Kokame K, Nobe Y, Kokubo Y. et al. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol 2005; 129: 93-100.
24 Budde U, Schneppenheim R, Plendl H. et al. Luminographic detection of von Willebrand factor multimers in agarose gels and on nitrocellulose membranes. Thromb Haemost 1990; 63: 312-315.
25 Studt JD, Budde U, Schneppenheim R. et al. Quantification and facilitated comparison of von Willebrand factor multimer patterns by densitometry. Am J Clin Pathol 2001; 116: 567-574.
26 Ruggeri ZM, Zimmerman TS. The complex multimeric composition of factor VIII/von Willebrand factor. Blood 1981; 57: 1140-1143.
27 Skjaerpe T, Hegrenaes L, Hatle L. Noninvasive estimation of valve area in patients with aortic stenosis by Doppler ultrasound and two-dimensional echocardiography. Circulation 1985; 72: 810-818.
28 Hatle L, Angelsen BA, Tromsdal A. Non-invasive assessment of aortic stenosis by Doppler ultrasound. Br Heart J 1980; 43: 284-292.
29 Gorlin R, Gorlin SG. Hydraulic formula for calculation of the area of the stenotic mitral valve, other cardiac valves, and central circulatory shunts. I. Am Heart J 1951; 41: 1-29.
30 Heilmann C, Geisen U, Beyersdorf F. et al. Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart. Thromb Haemost 2010; 103: 962-967.