Improvement of bleeding manifestations of acquired von Willebrand syndrome after balloon aortic valvoplasty in a child with aortic stenosis

2020 ◽  
pp. 101334
Author(s):  
Maria Carter-Febres ◽  
Kristi J. Smock ◽  
Adam L. Ware ◽  
Zeinab Afify
Keyword(s):  
Aortic Stenosis ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand

Predictors of Acquired Von Willebrand Syndrome in Patients with Aortic Stenosis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3318-3318 ◽  
Author(s):  
Dong Chen ◽  
Colleen S Thomas ◽  
Joseph L Blackshear
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Valve Replacement ◽  
Logistic Regression Analysis ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand ◽  
Time Velocity Integral ◽  
Valve Area

Abstract Abstract 3318 Background: Acquired von Willebrand syndrome (AVWS) due to loss of high molecular weight multimers (HMWM), is a frequent cause of bleeding in aortic stenosis (AS), and is reversed by valve replacement. The goal of this study was to explore predictors of AVWS in patients with AS. Methods: A total of 91 patients (59 men, median age 79 years) with AS (n=64) or heart valve replacement (n=27) were included. We recorded peripheral blood count, vital signs, mean gradient (MG), peak velocity (peak vel), aortic valve time velocity integral (AV-TVI), aortic valve area (AVA) and valve area index (AVAi), time velocity integral ratio (TVI ratio), VWF antigen (VWF:Ag), VWF activity by latex immunoturbidity assay (VWF:Lx), VWF multimer analysis, closure times of platelet function analyzer ADP and epinephrine cartridges (PFA-CADP and –CEPI). HMWM losses were graded as normal, mild or severe when compared to HMWM analyses of pooled plasma samples from normal donors. Potential predictors of HMWM loss were explored using logistic regression analysis. Results: Of the 91 patients, 42 (46%) had loss of HMWM (23 mild and 19 severe). In single variable logistic regression analysis, AVWS was associated with a low AVA (<1.0 cm2; OR=5.08, P<0.001), and low AVAi (<0.60 cm2/m2; OR=5.54, P<0.001), low TVI ratio (<0.25; OR=10.80, P<0.001), prolonged PFA-CADP (≥121 sec; OR=6.76, P<0.001), and low VWF:Lx/Ag (≤0.8; OR=8.06, P=0.008). Moderate peak vel (3–4 m/sec) and high peak vel (>4 m/sec) were associated with loss of HMWM (OR[vs. <3 m/sec]=5.80 and 37.70 respectively, P<0.001) as were moderate MG (25–40 mmHg) and high MG (>40 mmHg), (OR [vs. <25mmHg]=4.50 and 32.50 respectively, P<0.001). In exploratory multivariable analysis, mean gradient remained one of the strongest predictor of loss of HMWM. The estimated sensitivity of MG (≥25mmHg) in diagnosing AVWS was 83% (35/42, 95% CI: 69%-93%) and estimated specificity was 71% (35/49, 95% CI: 57%-83%). Considering the very strong correlation with mean gradient, we also considered the diagnostic utility of peak vel. Peak vel≥ 3 m/sec had a sensitivity of 89% (38/42, 95% CI: 77%-97%) and a specificity of 59% (29/49, 95% CI: 44%-73%) in detecting loss of HMWM. Conclusion: Our data suggest that mean gradient (>25 mmHg) and peak vel (≥ 3 m/sec), both derived from the Doppler aortic valve velocity envelope, are accurate predictors for AS-AVWS, and should be incorporated into algorithmic approaches to laboratory screening for AVWS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Utility of Various Von Willebrant Factor Laboratory Tests in Assessment of Acquired Von Willebrant Syndrome in Patients with Aortic Stenosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1517-1517
Author(s):  
Deepti M. Warad ◽  
Rachel Leger ◽  
Colleen S Thomas ◽  
Ewa M. Wysokinska ◽  
Matthew Auton ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Roc Curve ◽  
Conflicts Of Interest ◽  
Rank Correlation ◽  
Adenosine Diphosphate ◽  
Bleeding Tendency ◽  
Operating Characteristics ◽  
Acquired Von Willebrand Syndrome ◽  
Clinically Significant ◽  
Von Willebrand

Abstract Background: Aortic stenosis-associated acquired von Willebrand syndrome (AS-AVWS) is caused by an accelerated degradation of the highest molecular weight von Willebrand factor (VWF) multimers (HMWM). We recently reported that the severity of the HMWM loss correlates with the severity of AS and patients’ bleeding tendency (Am J Cardiol, 2013;111:374-81). As for the missing HMWM, it is still uncertain if they are cleared from circulation or redistributed with medium-low MWMs, which can be assessed by VWF propeptide (Pro)/antigen (Ag) ratio. Besides the tedious VWF multimer analysis, it is uncertain if VWF activity by immunoturbidic method (Lx)/ Ag ratio or VWF collagen binding activity (CBA)/Ag ratio can be used as a screening test to predict AS-AVWS. It has been speculated in the literature that VWF:CBA is more sensitive than VWF:Lx for detecting a HMWM loss. Our goal was to exam the laboratory characteristics of various VWF tests in evaluating AS-AVWS and the potential mechanism of HMWM loss. Method: Sixty-six patients (between years 2010-2012, 43% male) with varying degrees of AS (16 mild, 20 moderate, and 30 severe) and separate 21 patients who had aortic valve replacement were assessed with VWF:Ag, VWF:Lx, VWF:CBA, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer analysis and multimer ratio by densitometry (Am J Cardiol, 2013;111:374-81) after their echocardiography. The clinical endpoints of this study are AS severity measured by mean gradient (MG) by echocardiography and clinically significant bleeding. Statistical analyses including Spearman rank correlation test, estimation of the area under the receiver operating characteristics (ROC) curve, and Wilcoxon rank sum tests were performed. Results: VWF:Lx and VWF:CBA had strong correlation (Spearman r=0.94, P<0.001), and the correlation of VWF:CBA/Ag and VWF:Ltx/Ag was 0.49, p<0.001). As previously published, in patients with AS, MG correlated with VWF:Lx/Ag (Spearman r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). MG also correlated with VWF:CBA/Ag (r= -0.38, p=0.002), but not with VWF: Pro/Ag (r=-0.20, p=0.12). Among AS and AVR patients, the area under the ROC curve for detection of the loss of HMWM was 0.88 (95% CI: 0.80-0.95) by VWF multimer ratio, 0.76 (95% CI: 0.65-0.86) by PFA-CADP, 0.70 (95% CI: 0.58-0.82) by VWF:CBA/Ag ratio, 0.67 (95% CI: 0.56-0.70) by VWF:Lx/Ag ratio, and 0.53 (95% CI: 0.41-0.65) by VWF:Pro/Ag . In addition to previously published results, clinically significant bleeding, in 14% of AS patients, was not associated with VWF:CBA/Ag (p=0.25) or VWF:Pro/Ag ratio (p=0.83). VWF: CBA/Ag ratio was significantly lower in patients with severe AS (MG > 40 mmHg) compared to AVR patients (median: 0.84 vs. 1.06, p<0.001), while there was no evidence of a difference in VWF:Pro/Ag (p=0.45). Conclusion: HMWM losses are highly prevalent in patients with moderate to severe AS. Of the VWF tests, PFA-CADP and VWF multimer analysis and ratio had the highest predictive ability for AS-AVWS followed by VWF:CBA/Ag and VWF:Lx/Ag. The VWF:CBA is not overly superior than VWF:Lx for predicting a HMWM loss. The normal VWF:Pro/Ag suggests that AS-AVWS is different from other types of AVWS due to accelerated clearance of HMWM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Reappraising the spectrum of bleeding gastrointestinal angioectasia in a degenerative calcific aortic valve stenosis: Heyde’s syndrome

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Nelson Musilanga ◽  
Zhou Hongli ◽  
Cai Hongyu
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Elderly Patients ◽  
Gastrointestinal Bleeding ◽  
Deficiency Anemia ◽  
Management Approach ◽  
Acquired Von Willebrand Syndrome ◽  
Clinical Scenarios ◽  
Heyde’S Syndrome ◽  
Von Willebrand

Abstract Background The occurrence of bleeding gastrointestinal angioectasia in elderly patients with degenerative calcific aortic stenosis is one of the most challenging clinical scenarios. A number of studies have shown that this clinical phenomenon is known as Heyde’s syndrome. Main body of the abstract The pathogenesis of Heyde’s syndrome is mainly due to the loss of high-molecular-weight von Willebrand factor (HMW vWF) multimers, as a consequent fragmentation of HMW vWF multimers as they pass through the stenosed aortic valve leading to acquired von Willebrand syndrome type IIA. Aortic valve replacement has proven to be a more effective management approach in the cessation of recurrent episodes of gastrointestinal bleeding. Short conclusion Physicians should have a high index of suspicion when dealing with elderly patients with established aortic stenosis presenting with iron deficiency anemia or unclear gastrointestinal bleeding. Parallel consultations between different specialties are essential for appropriate management.

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.

scholarly journals Heyde Syndrome: An Unusual Cause of Gastrointestinal Bleeding

2021 ◽  
Vol 9 ◽  
pp. 232470962199727
Author(s):  
Dushyant Singh Dahiya ◽  
Asim Kichloo ◽  
El-Amir Zain ◽  
Jagmeet Singh ◽  
Farah Wani ◽  
...  
Keyword(s):  
Case Report ◽  
Aortic Stenosis ◽  
Severe Aortic Stenosis ◽  
Multisystem Disorder ◽  
Acquired Von Willebrand Syndrome ◽  
Transcatheter Aortic Valve ◽  
Replacement Procedure ◽  
Patient Reported ◽  
History Of ◽  
Von Willebrand

Heyde syndrome is a multisystem disorder characterized by the classical triad of aortic stenosis, gastrointestinal (GI) angiodysplasias, and acquired von Willebrand syndrome. GI angiodysplasias, common in older patients, are tortuous, thin-walled blood vessels seen in the mucosa or submucosa of the GI tract and are highly prone to rupture resulting in GI bleeds. In this case report, we describe an elderly female with a past medical history of end-stage renal disease and chronic anemia who presented to the emergency department (ED) with complaints of dark-tarry stools and associated abdominal cramping. Patient reported a history of dark-tarry stools and multiple blood transfusions in the past, secondary to severe anemia. An inpatient echocardiogram was performed, revealing severe aortic stenosis. Additionally, gastroenterology was consulted for esophagogastroduodenoscopy and colonoscopy, which were negative for active bleeding. About a year ago, the patient underwent capsule endoscopy at an outlying facility, which was positive for angiodysplasia. Therefore, due to high clinical suspicion, presence of aortic stenosis, and GI angiodysplasia, a platelet function assay was ordered. It was found to be abnormal, pointing to the presence of acquired von Willebrand syndrome. Hence, a diagnosis of Heyde syndrome was established. The patient gradually improved and was discharged with a follow-up appointment with the cardiologist for a possible transcatheter aortic valve replacement procedure. The patient underwent the procedure without complications, after which she did not report episodes of GI bleeding. In this case report, we discuss the presentation, pathophysiology, diagnostic approach, and management of patients with Heyde syndrome.

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