title: Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis.
abstract: Severe aortic stenosis is associated with a haemostatic abnormality that resembles acquired von Willebrand syndrome type 2. It is assumed that high shear conditions render large von Willebrand factor (VWF) multimers accessible to cleavage by ADAMTS-13. However, whether loss of these large multimers affects platelet function by impairing adhesion, aggregate formation, or both has not been evaluated in clinical studies. We prospectively enrolled 47 patients with severe aortic stenosis, and studied them prior to aortic valve surgery and at a median of six months after valve replacement. We investigated levels of large VWF multimers, platelet function under high shear conditions, and residual response to suboptimal concentrations of ADP to express P-selectin. As expected, there was a significant reduction of VWF large multimers before surgery that resolved thereafter in most patients (p<0.0001). The closure time of the ADP cartridge of the PFA-100 was also corrected in most patients after the operation (p<0.0001). We used the cone and plate(let) analyser Impact-R to differentiate between adhesion and aggregation. Both adhesion (p=0.03) and ADP-inducible platelet aggregation (p=0.002) improved considerably after valve replacement. Consequently, ADP-inducible expression of P-selectin was higher after valve replacement (p=0.001). We conclude that reduced levels of large VWF multimers associated with aortic stenosis lead to impairment of both adhesion and, especially, ADP-inducible platelet aggregation.
authors.affiliation: Department for Blood Group Serology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. simon.panzer@meduniwien.ac.at
authors.forename: S
authors.initials: S
authors.lastname: Panzer
authors.forename: R
authors.initials: R
authors.lastname: Badr Eslam
authors.forename: A
authors.initials: A
authors.lastname: Schneller
authors.forename: A
authors.initials: A
authors.lastname: Kaider
authors.forename: D
authors.initials: D
authors.lastname: Koren
authors.forename: B
authors.initials: B
authors.lastname: Eichelberger
authors.forename: R
authors.initials: R
authors.lastname: Rosenhek
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: I M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000097:blood*; D005260:Female; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D055503:Protein Multimerization; D014841:von Willebrand Factor / Q000737:chemistry / Q000502:physiology*
chemical_list: D019007:P-Selectin; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate