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.

scholarly journals Acquired von Willebrand disease caused by an autoantibody selectively inhibiting the binding of von Willebrand factor to collagen

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3378-3384 ◽  
Author(s):  
PJ van Genderen ◽  
T Vink ◽  
JJ Michiels ◽  
MB van 't Veer ◽  
JJ Sixma ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Binding Activity ◽  
Von Willebrand Disease ◽  
Low Grade ◽  
Bleeding Tendency ◽  
Glycoprotein Ib ◽  
Acquired Von Willebrand Disease ◽  
Recurrent Epistaxis ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract An 82-year-old man with a low-grade malignant non-Hodgkin lymphoma and an IgG3 lambda monoclonal gammopathy presented a recently acquired bleeding tendency, characterized by recurrent epistaxis, easy bruising, and episodes of melena, requiring packed red blood cell transfusions. Coagulation studies showed a von Willebrand factor (vWF) defect (Ivy bleeding time, > 15 minutes; vWF antigen [vWF:Ag], 0.08 U/mL; ristocetin cofactor activity [vWF:RCoF], < 0.05 U/mL; collagen binding activity [vWF:CBA], 0.01 U/mL; absence of the high molecular weight multimers of vWF on multimeric analysis). Mixing experiments suggested the presence of an inhibitor directed against the vWF:CBA activity of vWF without significantly inhibiting the FVIII:C, vWF:Ag, and vWF:RCoF activities. The inhibitor was identified as an antibody of the IgM class by immunoabsorption of vWF and inhibitor-vWF complexes from the plasma of the patient. Subsequent immunoprecipitation experiments using recombinant fragments of vWF showed that the inhibitor reacted with both the glycoprotein Ib binding domain (amino acids [aa] 422–826) and the A3 (aa 909–1112) domain of vWF, but not with the A2 (aa 716–908) or D4 (aa 1183–1535) domains. We conclude that the IgM autoantibody inhibits the vWF:CBA activity by reacting with an epitope present on both the glycoprotein Ib and A3 domains of vWF.

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.

A novel ELISA-based diagnosis of acquired von Willebrand disease with increased VWF proteolysis

2016 ◽  
Vol 115 (05) ◽  
pp. 950-959 ◽  
Author(s):  
Antoine Rauch ◽  
Claudine Caron ◽  
Flavien Vincent ◽  
Emmanuelle Jeanpierre ◽  
Catherine Ternisien ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Von Willebrand Disease ◽  
Ventricular Assist ◽  
Acquired Von Willebrand Syndrome ◽  
Acquired Von Willebrand Disease ◽  
Medical Need ◽  
Reliable Assessment ◽  
Left Ventricular Assist ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand disease-type 2A (VWD-2A) and acquired von Willebrand syndrome (AVWS) due to aortic stenosis (AS) or left ventricular assist device (LVAD) are associated with an increased proteolysis of von Willebrand factor (VWF). Analysis of VWF multimeric profile is the most sensitive way to assess such increased VWF-proteolysis. However, several technical aspects hamper a large diffusion among routine diagnosis laboratories. This makes early diagnosis and early appropriate care of increased proteolysis challenging. In this context of unmet medical need, we developed a new ELISA aiming a quick, easy and reliable assessment of VWF-proteolysis. This ELISA was assessed successively in a LVAD-model, healthy subjects (n=39), acquired TTP-patients (n=4), VWD-patients (including VWD-2A(IIA), n=22; VWD-2B, n=26; VWD-2A(IIE), n=21; and VWD-1C, n=8) and in AVWS-patients (AS, n=9; LVAD, n=9; and MGUS, n=8). A standard of VWF-proteolysis was specifically developed. Extent of VWF-proteolysis was expressed as relative percentage and as VWF proteolysis/VWF:Ag ratio. A speeddependent increase in VWF-proteolysis was assessed in the LVAD model whereas no proteolysis was observed in TTP-patients. In VWDpatients, VWF-proteolysis was significantly increased in VWD-2A(IIA) and VWD-2B and significantly decreased in VWD-2A(IIE) versus controls (p< 0.0001). In AVWS-patients, VWF-proteolysis was significantly increased in AS- and LVAD-patients compared to controls (p< 0.0001) and not detectable in MGUS-patients. A significant increase in VWFproteolysis was detected as soon as three hours after LVAD implantation (p< 0.01). In conclusion, we describe a new ELISA allowing a rapid and accurate diagnosis of VWF-proteolysis validated in three different clinical situations. This assay represents a helpful alternative to electrophoresis-based assay in the diagnosis and management of AVWS with increased VWF-proteolysis.Supplementary Material to this article is available online at www.thrombosis-online.com.

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.

Acquired von willebrand disease in multiple myeloma secondary to absorption of von willebrand factor by plasma cells

1990 ◽  
Vol 35 (2) ◽  
pp. 114-117 ◽  
Author(s):  
C. Richard ◽  
M. A. Cuadrado ◽  
M. Prieto ◽  
J. Batlle ◽  
M. Flópez Fernández ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Von Willebrand Factor ◽  
Plasma Cells ◽  
Von Willebrand Disease ◽  
Acquired Von Willebrand Disease ◽  
Von Willebrand ◽  
Willebrand Factor

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.

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