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Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis.
Thromb Haemost 2010; 103(2):408-14TH

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+Show Affiliations

Department for Blood Group Serology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. simon.panzer@meduniwien.ac.atNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20024494

Citation

Panzer, S, et al. "Loss of High-molecular-weight Von Willebrand Factor Multimers Mainly Affects Platelet Aggregation in Patients With Aortic Stenosis." Thrombosis and Haemostasis, vol. 103, no. 2, 2010, pp. 408-14.
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(2):408-14.
Panzer, S., Badr Eslam, R., Schneller, A., Kaider, A., Koren, D., Eichelberger, B., ... Lang, I. M. (2010). Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis. Thrombosis and Haemostasis, 103(2), pp. 408-14. doi:10.1160/TH09-06-0391.
Panzer S, et al. Loss of High-molecular-weight Von Willebrand Factor Multimers Mainly Affects Platelet Aggregation in Patients With Aortic Stenosis. Thromb Haemost. 2010;103(2):408-14. PubMed PMID: 20024494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis. AU - Panzer,S, AU - Badr Eslam,R, AU - Schneller,A, AU - Kaider,A, AU - Koren,D, AU - Eichelberger,B, AU - Rosenhek,R, AU - Budde,U, AU - Lang,I M, Y1 - 2009/12/18/ PY - 2009/06/22/received PY - 2009/11/06/accepted PY - 2009/12/22/entrez PY - 2009/12/22/pubmed PY - 2010/5/21/medline SP - 408 EP - 14 JF - Thrombosis and haemostasis JO - Thromb. Haemost. VL - 103 IS - 2 N2 - 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. SN - 2567-689X UR - https://www.unboundmedicine.com/medline/citation/20024494/Loss_of_high_molecular_weight_von_Willebrand_factor_multimers_mainly_affects_platelet_aggregation_in_patients_with_aortic_stenosis_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1160/TH09-06-0391 DB - PRIME DP - Unbound Medicine ER -