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OBJECTIVES Acquired von Willebrand syndrome, characterized by the reduction in von Willebrand factor (vWF) large multimers, has recently been considered as one of the causes of gastrointestinal bleeding (GIB). It remains unclear whether its haematological severity is linked with susceptibility to bleeding because the definition of the haematological severity of acquired von Willebrand syndrome has not been precisely determined. This study sought to establish a quantitative methodology to assess the haematological severity of acquired von Willebrand syndrome and to define the threshold for occurrence of GIB in patients implanted with left ventricular assist devices (LVADs). METHODS In total, 41 patients treated with continuous-flow LVAD implanted between 2011 and 2017 at Tohoku University Hospital were investigated. vWF large multimers were quantitatively evaluated using the 'vWF large multimer index' defined as the ratio of a large multimer proportion in total vWF derived from a patient to that from a normal control. Using this index, the amount of vWF large multimers was expressed as a percentage of its normal control value obtained with a simultaneous analysis of each time measurement. RESULTS Twelve (29%) patients developed GIB events during follow-up periods (median 591 days) after an LVAD implantation. The vWF large multimer index in patients with GIB was significantly lower than that in those without GIB (25.0 ± 10.3% vs 37.5 ± 17.8%, P  = 0.008). Most importantly, all patients experiencing GIB exhibited a vWF large multimer index below 40%. CONCLUSIONS Patients with GIB exhibited a more severe loss of vWF large multimers. The vWF large multimer index may dictate the risk of GIB after an LVAD implantation. Clinical trial registration number UMIN000018135. [ABSTRACT FROM AUTHOR]

Introduction: Acquired von Willebrand syndrome (aVWS), characterized by reduction in von Willebrand factor (vWF) large multimers, have recently been considered as a principal mechanism responsible for bleedings in patients with left ventricular assist device (LVAD). The hematological severity of aVWS varies from case to case even if the identical device is implanted. Hypothesis: We hypothesized that the diversity in hematological severity of aVWS is due to individual variability in vWF fragility in response to incremental shear stress. Methods: Whole blood samples derived from 20 healthy people were sheared at 20,000 to 40,000 s-1 using a custom-made shear stressor that can generate LVAD compatible shear stress. The amount of vWF large multimers was evaluated with our original vWF large multimer index. Results: Significant inverse correlation was observed between the level of vWF large multimer index and LVAD-compatible magnitude of shear stress exhibiting 64.7, 51.6, 31.8, 24.7 and 17.1% (median) of index at 20,000, 25,000, 30,000, 35,000, and 40,000 s-1 of shear stress, respectively. Furthermore, the values of vWF large multimer index were compatible with those derived from clinical implantable LVAD patients (median; 28.9%). With regard to the decrease patterns of vWF large multimer index corresponding to shear stress in each subject, they showed various changes remarkably (Fig). We found that the degradation patterns of the index can be characterized with three parameters, that is, the magnitude of initial drop; degree of reduction in the index at 20,000 s-1, ΔIndex; difference between the indices at 20,000 s-1 and 40,000 s-1, and Degradation slope; slope with a linear regression model. Conclusions: Significant individual variability in vWF fragility can be demonstrated quantitatively. The combined use of the novel high shear-loading device and quantitative evaluation of vWF large multimer may enable us to predict a bleeding risk by taking blood sample from each patient prior to LVAD implantation. [ABSTRACT FROM AUTHOR]

Fibromuscular dysplasia (FMD) is an arterial disease characterized by fibrous arterial wall thickening and irregular proliferation and degeneration of smooth muscle cells in muscular arteries. Abdominal aortic aneurysms (AAA) are rare, with only a few reported cases. A characteristic feature of AAA is an aneurysm protruding forward near the terminal aorta with stenosis. Here, we report a rare case of a 66-year-old woman who underwent abdominal aortic replacement for a fusiform AAA, diagnosed with aortic FMD (without stenotic lesions) on pathological examination., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Background: Severe aortic stenosis (AS) causes acquired von Willebrand syndrome by the excessive shear stress-dependent cleavage of high molecular weight multimers of von Willebrand factor (VWF). While the current standard diagnostic method is so-called VWF multimer analysis that is western blotting under nonreducing conditions, it remains unclear whether a ratio of VWF Ristocetin co-factor activity (VWF:RCo) to VWF antigen levels (VWF:Ag) of <0.7, which can be measured with an automated coagulation analyzer in clinical laboratories and is used for the diagnosis of hereditary von Willebrand disease., Objectives: To evaluated whether the VWF:RCo/VWF:Ag is useful for the diagnosis of AS-induced acquired von Willebrand syndrome., Methods: VWF:RCo and VWF:Ag were evaluated with the VWF large multimer index as a reference, which represents the percentage of a patient's VWF high molecular weight multimer ratio to that of standard plasma in the VWF multimer analysis., Results: We analyzed 382 patients with AS having transaortic valve maximal pressure gradients of >30 mmHg, 27 patients with peripheral artery disease, and 46 control patients free of cardiovascular disease with osteoarthritis, diabetes, and so on. We assumed a large multimer index of <80% as loss of VWF large multimers since 59.0% of patients with severe AS had the indices of <80%, while no control patients or patients with peripheral artery disease, except for 2 patients, exhibited the indices of <80%. The VWF:RCo/VWF:Ag ratios, measured using an automated blood coagulation analyzer, were correlated with the indices (r s  = 0.470, P  < .001). When the ratio of <0.7 was used as a cut-off point, the sensitivity and specificity to VWF large multimer indices of <80% were 0.437 and 0.826, respectively., Conclusion: VWF:RCo/VWF:Ag ratios of <0.7 may indicate loss of VWF large multimers with high specificity, but low sensitivity. VWF:RCo/VWF:Ag ratios in patients with AS having a ratio of <0.7 may be useful for monitoring the loss of VWF large multimers during their clinical courses., (© 2023 The Author(s).)