von Willebrand factor abnormalities in aortic valve stenosis: Pathophysiology and impact on bleeding

2011 ◽  
Vol 106 (07) ◽  
pp. 58-66 ◽  
Author(s):  
Sandro Sponga ◽  
Elena Pontara ◽  
Maria Grazia Cattini ◽  
Cristina Basso ◽  
Gaetano Thiene ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Von Willebrand Factor ◽  
Severe Aortic Stenosis ◽  
Valve Disease ◽  
Minor Bleeding ◽  
Acquired Von Willebrand Syndrome ◽  
Rheumatic Valve Disease ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryAcquired von Willebrand syndrome (AVWS) may complicate severe aortic valve stenosis, due to a reduction in the haemostatically more efficient large von Willebrand factor (VWF) multimers. This study was designed to analyse the relevance of VWF abnormalities and haemorrhagic diathesis in severe aortic valve stenosis. Forty-one consecutive patients undergoing valve replacement were investigated: seven had minor bleeding symptoms in their recent history; 10 (24.3%) had a reduced VWF collagen binding (VWF:CB) to VWF antigen ratio, and 33 (80.5%) had a decrease in large VWF multimers. The shortage of large multimers was not associated with any accumulation of small VWF multimers (apparently ruling out any increased VWF proteolysis), nor was there any increase in VWF propeptide, which excludes a shorter VWF survival. The risk of developing VWF abnormalities was higher in patients with rheumatic valve disease than in degenerative cases (p=0.025) and in valves with <50% of residual endothelial cells (p=0.004). Bleeders differed from non-bleeders in that they had a higher mean transvalvular gradient and a more marked decrease in large VWF multimers. VWF abnormalities did not exacerbate peri-operative blood loss, however – a finding consistent with the full correction of these VWF abnormalities, seen already on the first postoperative day and persisting for up to six months after surgery. According to the data obtained in our cohort of patients VWF abnormalities are common in severe aortic stenosis, particularly in cases of rheumatic valve disease, but loss of the largest multimers does not seem to cause clinical bleeding in most patients.

scholarly journals Severe Aortic Valve Stenosis

2016 ◽  
Vol 23 (3) ◽  
pp. 229-234 ◽  
Author(s):  
Rolf Dario Frank ◽  
Regina Lanzmich ◽  
Philipp K. Haager ◽  
Ulrich Budde
Keyword(s):  
Aortic Valve ◽  
Valve Replacement ◽  
Aortic Valve Stenosis ◽  
Binding Capacity ◽  
Valve Disease ◽  
Coagulation Activity ◽  
Acquired Von Willebrand Syndrome ◽  
Permanent Cure ◽  
Von Willebrand

Aortic valve stenosis (AVS) is the most common valve disease in adults. Severe forms are associated with acquired von Willebrand syndrome (aVWS) with loss of the largest von Willebrand factor (VWF) multimers. Diagnostic gold standard is the VWF multimer analysis. Valve replacement rapidly restores the VWF structure. Uncertainty exists if this effect is permanent and how functional VWF assays perform compared with multimer analysis. We studied 21 consecutive patients with severe AVS before and 6 to 18 months after valve surgery and compared them with 14 controls without valve disease referred for coronary angiography. The VWF multimers, VWF antigen (VWF:Ag), VWF collagen binding capacity (VWF:CB), VWF:CB/VWF:Ag ratio, in vitro bleeding time (PFA-100), factor VIII coagulation activity (FVIII:C), and VWF ristocetin cofactor activity (VWF:RCo) were determined. In all patients with AVS, the large VWF multimers were strongly reduced (56 ± 13% of normal plasma); all controls had normal multimers. The PFA-100 collagen/ADP closure times (coll/ADP CT) were prolonged in patients with AVS compared with the controls (175 ± 56 seconds vs 86 ± 14 seconds, P < .001). The VWF:CB/VWF:Ag ratio was pathological in 20 of the 21 patients but normal in controls. After surgery, the multimers normalized in all patients and coll/ADP CT shortened (pre 184 ± 65 seconds vs post 102 ± 22 seconds; P < .001). The VWF:CB/VWF:Ag ratio strongly improved ( P < .001) and normalized in 14 of 17 patients. In conclusion, all consecutive patients with severe AVS had an aVWS. The combination of coll/ADP CT and VWF:CB/VWF:Ag ratio detected the aVWS in all patients. More than 6 months after valve replacement, the VWF multimers were still normalized in all patients indicating a permanent cure of the aVWS.

scholarly journals Characterization of Von Willebrand Factor Multimer Structure in Patients With Severe Aortic Stenosis

2017 ◽  
Vol 24 (3) ◽  
pp. 496-501 ◽  
Author(s):  
Joerg Kellermair ◽  
Helmut W. Ott ◽  
Michael Spannagl ◽  
Josef Tomasits ◽  
Juergen Kammler ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Aortic Stenosis ◽  
Von Willebrand Factor ◽  
Severe Aortic Stenosis ◽  
Von Willebrand Disease ◽  
Acquired Von Willebrand Syndrome ◽  
Triplet Structure ◽  
Von Willebrand ◽  
Willebrand Factor

Acquired von Willebrand syndrome (AVWS) associated with severe aortic stenosis (AS) has been frequently subclassified into a subtype 2A based on the deficiency of high-molecular-weight (HMW) multimers as it is seen in inherited von Willebrand disease (VWD) type 2A. However, the multimeric phenotype of VWD type 2A does not only include an HMW deficiency but also a decrease in intermediate-molecular-weight (IMW) multimers and an abnormal inner triplet band pattern. These additional characteristics have not been evaluated in AVWS associated with severe AS. Therefore, we recruited N = 31 consecutive patients with severe AS and performed a high-resolution Western blot with densitometrical band quantification to characterize the von Willebrand factor (VWF) multimeric structure and reevaluate the AVWS subtype classification. Study patients showed an isolated HMW VWF multimer deficiency without additional abnormalities of the IMW portions and the inner triplet structure in 65%. In conclusion, the multimeric pattern of AVWS associated with severe AS does neither resemble that seen in AVWS type 2A nor that seen in inherited VWD type 2A. Therefore, a subclassification into a type 2A should not be used.

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

2012 ◽  
Vol 108 (07) ◽  
pp. 86-93 ◽  
Author(s):  
Sammy Elmariah ◽  
Louis Aledort ◽  
Jeffrey Dlott ◽  
Paul Stelzer ◽  
Jonathan Halperin ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Von Willebrand Factor ◽  
Multivariable Analysis ◽  
Acquired Von Willebrand Syndrome ◽  
Postoperative Changes ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIt 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.

The von Willebrand factor ratio and perioperative bleeding in patients with aortic valve stenosis

2019 ◽  
Vol 60 (1) ◽  
Author(s):  
Christina Brandenburger ◽  
Victoria Unislawski ◽  
Ulrich Budde ◽  
Armin Zittermann ◽  
Jan Gummert ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Von Willebrand Factor ◽  
Perioperative Bleeding ◽  
Factor Ratio ◽  
Von Willebrand ◽  
Willebrand Factor

Transcatheter aortic valve implantation in a patient with suspected hereditary von Willebrand disease and severe gastrointestinal bleeding – a case report

2019 ◽  
Vol 64 (4) ◽  
pp. 142-147 ◽  
Author(s):  
Moritz Mirna ◽  
Michael Lichtenauer ◽  
Thomas Theurl ◽  
Mathias Ausserwinkler ◽  
Albert Topf ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Gastrointestinal Bleeding ◽  
Aortic Valve Stenosis ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Transcatheter Aortic Valve ◽  
Aortic Valve Implantation ◽  
Valve Implantation ◽  
Von Willebrand ◽  
Willebrand Factor

Introduction von Willebrand disease is the most common hereditary coagulopathy and is characterised by a deficiency in the quantity or quality of the von Willebrand factor. Heyde Syndrome, in contrast, is an acquired form of von Willebrand syndrome (AVWS) due to calcific aortic valve stenosis, characterised by gastrointestinal bleeding from angiodysplasia. Case presentation A 73-year-old patient presented with severe gastrointestinal bleeding and stated that she suffered from hereditary von Willebrand disease. Upon echocardiography, a severe aortic valve stenosis was found, and hence the suspicion of additional AVWS was raised. Since endoscopic interventions and conservative therapeutic approaches did not result in a cessation of the bleeding, transcatheter aortic valve implantation (TAVI) was performed to stop the additional shear stress on von Willebrand factor. This resulted in cessation of the bleeding. Conclusion Retrospectively, this life-threatening gastrointestinal bleeding was a result of severe Heyde Syndrome, which could be alleviated by TAVI. Whether the patient had suffered from inherited von Willebrand disease in the past, remains uncertain. AVWS should be considered in patients with suspected inherited von Willebrand disease and concomitant severe aortic valve stenosis, since it constitutes a treatable cause of a potentially severe bleeding disorder.

Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis

2010 ◽  
Vol 103 (02) ◽  
pp. 408-414 ◽  
Author(s):  
Roza Badr Eslam ◽  
Alexandra Schneller ◽  
Alexandra Kaider ◽  
Daniela Koren ◽  
Beate Eichelberger ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Aortic Stenosis ◽  
Valve Replacement ◽  
Platelet Function ◽  
Von Willebrand Factor ◽  
Severe Aortic Stenosis ◽  
High Shear ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor

SummarySevere 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.

Von Willebrand factor multimers during non-invasive ultrasound therapy for aortic valve stenosis

Angiogenesis ◽  
2021 ◽  
Author(s):  
David M. Smadja ◽  
Guillaume Goudot ◽  
Nicolas Gendron ◽  
Samuel Zarka ◽  
Etienne Puymirat ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Von Willebrand Factor ◽  
Ultrasound Therapy ◽  
Non Invasive ◽  
Von Willebrand ◽  
Willebrand Factor
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