Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement

Gragnano, Felice; Crisci, Mario; Bigazzi, Maurizio Cappelli; Bianchi, Renatomaria; Sperlongano, Simona; Natale, Francesco; Fimiani, Fabio; Concilio, Claudia; Cesaro, Arturo; Pariggiano, Ivana; Diana, Vincenzo; Limongelli, Giuseppe; Cirillo, Plinio; Russo, Maria Giovanna; Golia, Enrica; Calabrò, Paolo

doi:10.1177/0003319717708070

Cited by 11 publications

(10 citation statements)

References 76 publications

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“…Interestingly, our distinctly larger RETORT‐MR trial could not confirm these results. Besides the considerably different sample sizes, which could have biased the results preferentially in smaller trials, the main reason for this finding could be the time when vWFAct and vWFAg were measured: Gragnano et al analyzed vWFAct and vWFAg levels already 24 hours after percutaneous mitral valve repair, 1 whereas our study presents the levels of vWFAct and vWFAg not earlier than 4 weeks after MitraClip implantation. We deliberately chose this point of time to avoid the influence of the TMVR procedure and general anesthesia on hemostasis as it is known that stress may cause fluctuation of vWF levels 23 with unclear functional relevance.…”

Section: Discussionmentioning

confidence: 83%

“…Similarly, the presence of AvWS has been described in patients with moderate to severe mitral valve dysfunction 1 . Blackshear et al investigated a population of 53 patients with mild to severe mitral regurgitation and reported that more severe mitral valve regurgitation was associated with progressive worsening of vWF activity and bleeding tendency 17 .…”

Section: Introductionmentioning

confidence: 93%

“…Von Willebrand factor (vWF) is produced in megakaryocytes and endothelial cells and functions as a large human adhesive glycoprotein 1,2 …”

Section: Introductionmentioning

confidence: 99%

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Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Meindl

Paulus

Koller

et al. 2020

Clinical Cardiology

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Background and Hypothesis The acquired von Willebrand syndrome (AvWS), which predisposes to bleeding events, is often related to valvular heart diseases. We investigated possible implications of AvWS and factor VIII levels in patients with moderate to severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR). Methods and Results 123 patients with moderate to severe MR were prospectively enrolled. Complete measurements of von Willebrand Factor activity (vWFAct), von Willebrand Factor antigen (vWFAg), and factor VIII expression before and 4 weeks after TMVR were available in 85 patients. At baseline, seven patients had a history of gastrointestinal bleeding, two patients suffered bleeding events during their hospital stay, and one patient had a bleeding 4 weeks after TMVR. Even though vWFAct, vWFAct/vWFAg ratio and vWFAg values did not change after TMVR, we observed a significantly lower vWFAct/vWFAg ratio in patients with primary MR as compared to patients with secondary MR both at baseline (p = 0.022) and 4 weeks following the TMVR procedure (p = 0.003). Additionally, patients with a mean mitral valve gradient ≥4 mmHg after TMVR had significantly lower vWFAct/vWFAg ratios as compared to patients with a mean mitral valve gradient <4 mmHg (p = 0.001). Conclusions MR of primary etiology was associated with lower vWFAct/vWFAg ratio, hinting toward HMWM loss due to shear stress caused by eccentric regurgitation jets. In addition, morphological changes leading to postprocedural transmitral gradients ≥4 mmHg were related to lower vWFAct/vWFAg ratio 4 weeks after the procedure. Alterations of the vWFAct/vWFAg ratio in turn did not translate into a greater risk for bleeding events.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 93%

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Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Meindl

Paulus

Koller

et al. 2020

Clinical Cardiology

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“…Approximately 21% of patients with aVWS will have shear-induced activation of ADAMTS13 such as AS, hypertrophic cardiomyopathy, ventricular septal defect, left ventricular assist device, or pulmonary hypertension [ 3 ]. With regard to laboratory findings, an average of 20%-70% of moderate to severe AS patients will have increased removal of high molecular weight vWF [ 4 ]. There are a wide variety of GI pathologies that affect the elderly.…”

Section: Discussionmentioning

confidence: 99%

Aortic Stenosis Complicated by Gastrointestinal Arteriovenous Malformations: It is not Always Heyde Syndrome

Thakker¹,

Suthar²,

Kline³

et al. 2020

Cureus

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Aortic stenosis (AS) and arteriovenous malformations (AVM) are a common coexisting pathology in the elderly. When both pathologies are combined, Heyde syndrome is a differential that is widely explored among clinicians. Unfortunately, this may not always be the case. We present a case of an 82-year-old female admitted for acute gastrointestinal (GI) bleeding with a history of AVMs and AS, as well as, an algorithm in diagnosing elderly patients with both pathologies.

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“…20 Otherwise, an excessive clearance of VWF multimers by ADAMTS-13 under high shear stress (i.e., congenital heart disease, aortic stenosis, and mitral regurgitation) may result in bleeding diathesis and an acquired von Willebrand syndrome. 21 An imbalance in VWF/ADAMTS-13 axis is also involved in common thrombotic disorders, such as stroke, coronary artery disease, and venous thromboembolism (VTE). 22…”

Section: Vwf Activity Modulation: the Role Of Adamts-13mentioning

confidence: 99%

von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

Calabrò

Gragnano

Golia

et al. 2017

Semin Thromb Hemost

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Venous thromboembolism (VTE) is a frequent cause of disability and mortality worldwide. Von Willebrand factor (VWF) is a major determinant of hemostasis and clot formation, in both arteries and veins. Although VWF is mainly known for its role in arterial thrombosis, several studies suggest a pathogenic role for VWF and its regulator ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in venous thrombosis. Nongenetic and genetic factors, including gene mutations and polymorphisms, aging, hormone status, ABO blood groups, and systemic inflammation, have been involved in the modulation of both VTE predisposition and plasma levels of VWF. In several clinical settings, including inflammatory disease and cancer, VWF and ADAMTS-13 are currently investigated as possible determinants of vein thrombosis. These data indicate VWF as a potential therapeutic target in the management of VTE. Several studies report unselective antagonism of VWF for drugs used in daily clinical practice, including heparin and statins. Selective inhibition of VWF pathway has recently been tested in animal models of arterial and venous thrombosis as a novel therapeutic strategy to prevent platelet aggregation and thrombosis, promote vein lumen recanalization, and improve vein valve competency with excellent safety profile. In this review, we summarize the role of VWF in VTE, focusing on clinical and potential therapeutic implications.

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Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement

Cited by 11 publications

References 76 publications

Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Aortic Stenosis Complicated by Gastrointestinal Arteriovenous Malformations: It is not Always Heyde Syndrome

von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

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