Singularities of haemorrhagic syndrome in children with native and acquired deficiencies of von Willebrand factor

2013 ◽  
Vol 4 (1) ◽  
pp. 78-85
Author(s):  
Kseniya Ivanovna Pshenichnaya ◽  
Yegor Viktorovich Lyugayev ◽  
Olga Georgiyevna Golovina
Keyword(s):  
Clinical Manifestation ◽  
Von Willebrand Factor ◽  
Clinical Studies ◽  
Clinical Manifestations ◽  
Underlying Disease ◽  
Von Willebrand Disease ◽  
Acquired Von Willebrand Syndrome ◽  
Different Types ◽  
Von Willebrand ◽  
Willebrand Factor

Deficiencies of content in blood and activity of von Willebrand factor can be inborn or acquired with diseases of different nature. Acquired deficiencies of von Willebrand factor or acquired von Willebrand syndrome in children have been described in several clinical studies. This research paper contains data on clinical manifestation and dynamics of haemorrhagic syndrome in 30 children between 13 months and 18 years of age with acquired von Willebrand factor, suffering from different types of pathology. Similarly, clinical manifestations and dynamics of angiostaxis have been studied in 33 children with von Willebrand disease. It has been determined that clinical manifestations of microcirculatory angiostaxis are the same for children from both groups; however, children with acquired von Willebrand syndrome showed dominating limited numbers of haemorrhagical symptoms that were shorter in duration and less intense. Besides, hematomic component of haemorrhagic syndrome was absent. Eventually, accompanied by positive dynamic of the underlying disease, relapses of haemorrhagic syndrome cease, which does not happen in case of the patients with von Willebrand disease.

Quantitative Analysis of von Willebrand Factor and Its Propeptide in Plasma in Acquired von Willebrand Syndrome

1998 ◽  
Vol 80 (09) ◽  
pp. 495-498 ◽  
Author(s):  
Ria Boertjes ◽  
Jan van Mourik ◽  
Perry van Genderen
Keyword(s):  
Quantitative Analysis ◽  
Von Willebrand Factor ◽  
Intravenous Immunoglobulins ◽  
Von Willebrand Disease ◽  
High Dose ◽  
Type I ◽  
Acquired Von Willebrand Syndrome ◽  
Normal Individuals ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryMeasurement of the von Willebrand factor (vWF) propeptide, also known as von Willebrand antigen II, has been suggested to be helpful in the discrimination of congenital von Willebrand disease type I from type 2 and in assessing the extent of activation of the endothelium. We performed a quantitative analysis of mature vWF and its propeptide in plasma in 8 patients with acquired von Willebrand syndrome (AvWS) and in 20 normal individuals. Mature vWF levels were significantly lower in AvWS as compared with normal individuals (13.4 ± 3.5 vs 35.6 ± 3.3 nM, p <0.001). In contrast, propeptide levels were significantly higher in AvWS (11.4 ± 1.1 vs 4.7 ± 0.2 nM, p < 0.001), probably reflecting a compensatory increase in vWF synthesis or increased perturbation of the endothelium in AvWS. After treatment with DDAVP, propeptide and mature vWF levels rose 5-fold in AvWS, whereas propeptide levels were not altered by the infusion of a vWF concentrate or treatment with high dose intravenous immunoglobulins, indicating that plasma propeptide levels are a reliable reflection of vWF synthesis. Measurement of propeptide levels may provide additional information in AvWS as to whether decreased levels of mature vWF in the circulation are due to a decrease in synthesis or due to an accelerated removal of vWF from the circulation.

Diagnosis and Management of Acquired von Willebrand Disease in Heart Disease: A Review of the Literature

2018 ◽  
Vol 68 (03) ◽  
pp. 200-211
Author(s):  
Mate Petricevic ◽  
Jadranka Knezevic ◽  
Gordan Samoukovic ◽  
Bozena Bradaric ◽  
Ivica Safradin ◽  
...  
Keyword(s):  
Heart Disease ◽  
Von Willebrand Factor ◽  
Structural Heart Disease ◽  
Von Willebrand Disease ◽  
Circulatory Support ◽  
Mechanical Destruction ◽  
Acquired Von Willebrand Syndrome ◽  
Acquired Von Willebrand Disease ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe incidence of acquired von Willebrand syndrome (AvWS) in patients with heart disease is commonly perceived as rare. However, its occurrence is underestimated and underdiagnosed, potentially leading to inadequate treatment resulting in increased morbidity and mortality.In patients with cardiac disease, AvWS frequently occurs in patients with structural heart disease and in those undergoing mechanical circulatory support (MCS).The clinical manifestation of an AvWS is usually characterized by apparent or occult gastrointestinal (GI) or mucocutaneous hemorrhage frequently accompanied by signs of anemia and/or increased bleeding during surgical procedures. The primary change is loss of high-molecular weight von Willebrand factor multimers (HMWM). Whereas the loss of HMWM in patients with structural heart disease is caused by increased HMWM cleavage by von Willebrand factor (vWF)-cleaving protease, ADAMTS13, AvWS in MCS patients is predominantly a result of a high shear stress coupled with mechanical destruction of vWF itself.This manuscript provides a comprehensive review of the evidence regarding both diagnosis and contemporary management of AVWS in patients with heart disease.

Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura

2014 ◽  
Vol 34 (03) ◽  
pp. 215-225 ◽  
Author(s):  
R. Schneppenheim ◽  
U. Budde
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Active Phase ◽  
Von Willebrand Disease ◽  
Bleeding Tendency ◽  
Thrombocytopenic Purpura ◽  
Acquired Von Willebrand Syndrome ◽  
Key Factor ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weight multimers (VWF-HMWM) or their pathologically enhanced degradation under - lies a particular type of von Willebrand disease, VWD type 2A with a significant bleeding tendency, and may also be observed in acquired von Willebrand syndrome due to cardiovascular disease. In these conditions multimer analysis is an obligatory and powerful tool for diagnosis of VWD. The opposite condition, the persistence of ultralarge VWF (UL-VWF) multimers may cause the microangiopathic life-threatening disorder thrombotic thrombocytopenic purpura (TTP). During the course of active TTP, UL-VWF is consumed in the hyaline thrombi formed in the microvasculature which will ultimately result in the loss of UL-VWF and VWF-HMWM. Therefore, VWF multimer analysis is not a valid tool to diagnose TTP in the active phase of disease but may be helpful for the diagnosis of TTP patients in remission.

Treatment of Acquired von Willebrand Syndrome in Patients With Monoclonal Gammopathy of Uncertain Significance: Comparison of Three Different Therapeutic Approaches

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2707-2711 ◽  
Author(s):  
Augusto B. Federici ◽  
Federica Stabile ◽  
Giancarlo Castaman ◽  
Maria Teresa Canciani ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Term Therapy ◽  
High Dose ◽  
Therapeutic Approaches ◽  
Acquired Von Willebrand Syndrome ◽  
Uncertain Significance ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Patients with monoclonal gammopathies of uncertain significance (MGUS) may develop an acquired bleeding disorder similar to congenital von Willebrand disease, called acquired von Willebrand syndrome (AvWS). In these patients, measures to improve hemostasis are required to prevent or treat bleeding episodes. We diagnosed 10 patients with MGUS and AvWS: 8 had IgGκ (3) or λ (5) MGUS and 2 IgM-κ MGUS. Three therapeutic approaches were compared in them: (1) desmopressin (DDAVP), (2) factor VIII/von Willebrand factor (FVIII/vWF) concentrate, and (3) high-dose (1 g/kg/d for 2 days) intravenous Ig (IVIg). In patients with IgG-MGUS, DDAVP and FVIII/vWF concentrate increased factor VIII and von Willebrand factor in plasma, but only transiently. IVIg determined a more sustained improvement of the laboratory abnormalities and prevented bleeding during surgery (short-term therapy). In addition to the standard 2-day infusion protocol, a long-term IVIg therapy was performed in 2 patients with IgG-MGUS: repeated (every 21 days) single infusions of IVIg did improve laboratory abnormalities and stopped chronic gastrointestinal bleeding. On the other hand, IVIg failed to correct laboratories abnormalities in patients with IgM-MGUS. These comparative data obtained in a relative large and homogeneous group of patients with AvWS and MGUS confirm that DDAVP and FVIII/vWF concentrates improve the bleeding time (BT) and FVIII/vWF measurements only transiently, whereas IVIg provides a sustained treatment of AvWS associated with IgG-MGUS, but not with IgM-MGUS. © 1998 by The American Society of Hematology.

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.

Treatment of Acquired von Willebrand Syndrome in Patients With Monoclonal Gammopathy of Uncertain Significance: Comparison of Three Different Therapeutic Approaches

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2707-2711
Author(s):  
Augusto B. Federici ◽  
Federica Stabile ◽  
Giancarlo Castaman ◽  
Maria Teresa Canciani ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Term Therapy ◽  
High Dose ◽  
Therapeutic Approaches ◽  
Acquired Von Willebrand Syndrome ◽  
Uncertain Significance ◽  
Von Willebrand ◽  
Willebrand Factor

Patients with monoclonal gammopathies of uncertain significance (MGUS) may develop an acquired bleeding disorder similar to congenital von Willebrand disease, called acquired von Willebrand syndrome (AvWS). In these patients, measures to improve hemostasis are required to prevent or treat bleeding episodes. We diagnosed 10 patients with MGUS and AvWS: 8 had IgGκ (3) or λ (5) MGUS and 2 IgM-κ MGUS. Three therapeutic approaches were compared in them: (1) desmopressin (DDAVP), (2) factor VIII/von Willebrand factor (FVIII/vWF) concentrate, and (3) high-dose (1 g/kg/d for 2 days) intravenous Ig (IVIg). In patients with IgG-MGUS, DDAVP and FVIII/vWF concentrate increased factor VIII and von Willebrand factor in plasma, but only transiently. IVIg determined a more sustained improvement of the laboratory abnormalities and prevented bleeding during surgery (short-term therapy). In addition to the standard 2-day infusion protocol, a long-term IVIg therapy was performed in 2 patients with IgG-MGUS: repeated (every 21 days) single infusions of IVIg did improve laboratory abnormalities and stopped chronic gastrointestinal bleeding. On the other hand, IVIg failed to correct laboratories abnormalities in patients with IgM-MGUS. These comparative data obtained in a relative large and homogeneous group of patients with AvWS and MGUS confirm that DDAVP and FVIII/vWF concentrates improve the bleeding time (BT) and FVIII/vWF measurements only transiently, whereas IVIg provides a sustained treatment of AvWS associated with IgG-MGUS, but not with IgM-MGUS. © 1998 by The American Society of Hematology.

scholarly journals Evaluation of the Utility of von Willebrand Factor Propeptide in the Differential Diagnosis of von Willebrand Disease and Acquired von Willebrand Syndrome

2018 ◽  
Vol 45 (01) ◽  
pp. 036-042 ◽  
Author(s):  
Francesca Stufano ◽  
Marco Boscarino ◽  
Paolo Bucciarelli ◽  
Luciano Baronciani ◽  
Alberto Maino ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Von Willebrand Factor ◽  
Characteristic Curve ◽  
Von Willebrand Disease ◽  
Cross Sectional ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Von Willebrand Factor Propeptide

AbstractAn increased von Willebrand factor propeptide (VWFpp) to VWF antigen (VWF:Ag) ratio (VWFpp/VWF:Ag) indicates an enhanced clearance of VWF. This finding has been described in von Willebrand disease (VWD) and in acquired von Willebrand syndrome (AVWS). A distinction between these two diseases, one congenital and the other acquired, is primarily based on family and personal history of bleeding. However, if this information is scanty, the diagnosis might be challenging due to the lack of an effective diagnostic biomarker. In this cross-sectional study, we assessed the ability of VWFpp/VWF:Ag for the differential diagnosis between VWD and AVWS. VWFpp/VWF:Ag was measured in a group of 153 patients (125 with VWD and 28 with AVWS). Most patients with AVWS and VWD showed an increased VWFpp/VWF:Ag, although to variable degrees. A marked increase of VWFpp/VWF:Ag was mainly associated with the diagnosis of AVWS and VWD type 1 Vicenza. A receiver operating characteristic curve was used to identify the optimal cutoff of VWFpp/VWF:Ag for discrimination of patients with a modestly increased (most VWD cases) versus those with a markedly increased clearance (AVWS and VWD type 1 Vicenza), and this cutoff was identified at the value of 3.9 (sensitivity: 0.70, specificity: 0.97). The ROC curve sorting from a logistic model containing VWFpp/VWF:Ag, age, and sex had an area under the curve (AUC) of 0.88 (95% confidence interval: 0.80–0.95). A subsequent molecular evaluation discriminated VWD type 1 Vicenza from AVWS. In conclusion, VWFpp/VWF:Ag appears helpful to discriminate patients with a markedly increase VWF clearance (AVWS or VWD type 1 Vicenza) from those with a modestly increased clearance (most VWD patients).

scholarly journals von Willebrand factor regulation of blood vessel formation

Blood ◽  
2018 ◽  
Vol 132 (2) ◽  
pp. 132-140 ◽  
Author(s):  
Anna M. Randi ◽  
Koval E. Smith ◽  
Giancarlo Castaman
Keyword(s):  
Blood Vessel ◽  
Von Willebrand Factor ◽  
Critical Role ◽  
Von Willebrand Disease ◽  
In Vivo Studies ◽  
Acquired Von Willebrand Syndrome ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractSeveral important physiological processes, from permeability to inflammation to hemostasis, take place at the vessel wall and are regulated by endothelial cells (ECs). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for von Willebrand factor (VWF), a large glycoprotein best known for its critical role in hemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularization, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth EC (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel-Palade bodies, such as angiopoietin-2 and galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor signaling. Recent studies suggest that the roles of VWF may be tissue specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding resulting from vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high-molecular-weight multimers in regulating angiogenesis, and review the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome.

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