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(Circulation. 2000;102:1290.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Proteolysis of von Willebrand Factor and Shear Stress–Induced Platelet Aggregation in Patients With Aortic Valve Stenosis

F. I. Pareti, MD; A. Lattuada, BSc; C. Bressi, BSc; M. Zanobini, MD; A. Sala, MD; A. Steffan, MD; Z. M. Ruggeri, MD

From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Department of Internal Medicine (F.I.P., A.L., C.B.), IRCCS Maggiore Hospital, Milan; Chair of Cardiac Surgery (M.Z.), Fondazione Monzino, Milan; Division of Cardiac Surgery (A. Sala), Ospedale di Circolo, Fondazione Macchi, Varese; and the Departments of Blood Transfusion and Clinical Pathology (A. Steffan), IRCCS-CRO, Aviano, Italy; and the Departments of Molecular and Experimental Medicine and of Vascular Biology (Z.M.R.), The Scripps Research Institute, La Jolla, Calif.

Correspondence to F.I. Pareti, Department of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan, Italy. E-mail Francesco.Pareti{at}unimi.it

Background—Excessive bleeding may complicate congenital cardiac defects. To explain the pathogenesis of this abnormality, we evaluated selected parameters of primary hemostasis in patients with aortic valve stenosis before and after corrective surgery.

Methods and Results—We examined shear-induced platelet aggregation with the filter aggregometer test and von Willebrand factor (vWF) structure by evaluating the multimeric distribution and extent of subunit proteolysis. The platelet count was reduced before corrective surgery, and shear-induced platelet aggregation was impaired. Moreover, vWF multimers of higher molecular mass were decreased, and proteolytic subunit fragments were increased. After correction of the cardiac defect, all of these parameters returned to normal.

Conclusions—Alterations of vWF and platelet function may contribute to the bleeding diathesis in patients with aortic valve stenosis. Improvement after corrective surgery suggests that the passage of blood through a stenosed aortic valve may result in shear forces that induce vWF interaction with platelets in the circulation and, in turn, trigger platelet clearance, vWF degradation, and the impairment of primary hemostasis.

Key Words: von Willebrand factor • platelets • stenosis • valves

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