Acquired von Willebrand Syndrome with Mechanical Circulatory Support

2019 ◽  
pp. 269-276
Author(s):  
Evan C. Klein ◽  
Lisa Baumann Kreuziger
Keyword(s):  
Molecular Weight ◽  
Von Willebrand Factor ◽  
Mechanical Circulatory Support ◽  
Axial Flow ◽  
Circulatory Support ◽  
Severe Bleeding ◽  
Acquired Von Willebrand Syndrome ◽  
Mechanical Circulatory Support Devices ◽  
Von Willebrand ◽  
Willebrand Factor

Acquired von Willebrand syndrome occurs in the setting of mechanical circulatory support from device-associated sheer stress, which changes the quaternary structure of high-molecular-weight von Willebrand factor multimers, exposing the cleavage site for ADAMTS-13. Once cleaved, lower-molecular-weight multimers lose their affinity for binding platelets, increasing the susceptibility to bleeding complications. Acquired von Willebrand syndrome has been described in all the currently approved continuous-flow mechanical circulatory support devices. Although theoretically the risk of von Willebrand factor multimer degradation is increased at the higher rotational speeds of axial-flow pumps, disease severity does not differ greatly between axial- and centrifugal-flow devices. Disease-specific therapies for acquired von Willebrand syndrome have not been well studied in patients supported by mechanical circulatory devices. Case reports and case series have noted beneficial effects from octreotide, doxycycline, desmopressin, or Humate-P treatment for patients with recurrent severe bleeding.

The influence of surface roughness on the damage of von Willebrand Factor under shear flow condition

2021 ◽  
pp. 039139882110569
Author(s):  
Xu Mei ◽  
Bin Lu ◽  
Min Zhong ◽  
Yuxin Zhu ◽  
Liudi Zhang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Surface Roughness ◽  
Flow Condition ◽  
Mechanical Circulatory Support ◽  
Circulatory Support ◽  
Blood Damage ◽  
Mechanical Circulatory Support Devices ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Support Devices

Despite technological advances in mechanical circulatory support devices to treat end-stage heart failure, blood damage induced by non-physiological shear stress in operation often triggered clinical hemocompatibility complications. The loss of high molecular weight von Willebrand Factor (HMW-VWF) has been considered as an essential cause of gastrointestinal bleeding. In addition to the mechanics factors, interface factors may also affect blood damage, especially the surface characteristics. In this study, the effect of surface roughness on VWF damage under flow condition was investigated. A roller pump circulation experimental platform with a roughness embedded sample chamber was constructed to provide blood shearing flow condition. VWF molecular weight analysis, VWF antigen (VWF-Ag) concentration assay, and VWF ristocetin cofactor activity (VWF-Rico) assay were performed on the sheared blood samples. These variables are the main functional indicators of VWF. It was found that the surface roughness induced VWF damage is mainly caused by the loss of HMW-VWF rather than reducing the total amount of VWF. The threshold value of surface roughness for a rapid increase in the degradation of HMW-VWF under low flow rate was obtained between Ra 0.4 and 0.6 μm, which was smaller than the threshold for hemolysis. Our findings indicated that VWF is more sensitive to the interface factor of surface roughness than red blood cells, thus has a higher requirement for blood pump design. It could provide reference for the material design and processing in developing mechanical circulatory support devices.

scholarly journals Clinical Significance of Inhibitors in Acquired von Willebrand Syndrome

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3623-3629 ◽  
Author(s):  
Hiroshi Mohri ◽  
Shigeki Motomura ◽  
Heiwa Kanamori ◽  
Michio Matsuzaki ◽  
Shin-ichiro Watanabe ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Immunoglobulin Therapy ◽  
High Dose ◽  
Severe Bleeding ◽  
Bleeding Tendency ◽  
Intravenous Immunoglobulin Therapy ◽  
Acquired Von Willebrand Syndrome ◽  
Underlying Diseases ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Of 260 patients enrolled, 25 patients (9.6%) were associated with acquired von Willebrand syndrome (AvWS). We studied 25 patients with AvWS, retrospectively. AvWS was diagnosed by reduced levels of von Willebrand factor (vWF) (decrease of von Willebrand factor antigen [vWF:Ag] and von Willebrand ristocetin cofactor [vWF:RCoF]), a decrease of ristocetin-induced platelet agglutination (RIPA), sometimes decreased high-molecular-weight multimers, and prolonged bleeding time with neither prior nor family histories of bleeding problems and the evidence of normal vWF:RCoF in their families. The inhibitor of vWF was determined by mixing patient plasma with pooled normal plasma. Eight patients in this study had the inhibitors to vWF that were of the IgG class; the subclasses were IgG1 (7 cases) and IgG2 (1 case). Multimeric analysis of vWF showed selective loss of large multimers in most patients with AvWS similar to that of congenital type-2 von Willebrand disease (vWD). All inhibitors blocked ristocetin-mediated vWF binding to platelets. Five out of 6 IgGs evaluated here recognized the 39/34-kD fragment (residues 480/481-718) and Fragment III (residues 1-1365) that implied binding domain of glycoprotein Ib (GPIb), whereas 1 recognized Fragment I (residues 911-1365). A close relationship was found between the presence of the inhibitor and bleeding tendency. Of the 7 patients with inhibitors, 6 patients (86%) had a bleeding tendency, as well as 1 of the 15 patients without inhibitors (6%). The efficacy of treatment of underlying diseases and/or therapy with deamino D-arginine vasopressin (DDAVP) for the treatment of AvWS also depends on the presence of an inhibitor. Four of 8 patients with inhibitors (50%) had poor response to treatment of the underlying disease and/or therapy with DDAVP, as well as 1 of the 16 patients without inhibitors (6%). These results indicate that patients with AvWS developing inhibitors to vWF are likely to have bleeding problems and might be resistant to treatment of underlying diseases and/or therapy with DDAVP for bleeding to AvWS. We also showed evidence that intravenous immunoglobulin therapy (0.3 g/kg, 3 days) was effective to correct a hemostatic defect and manage severe bleeding in a patient with AvWS developing inhibitors. We might consider an additional treatment including expensive high-dose immunoglobulin therapy when uncontrollable bleeding is continued after the treatment of the underlying diseases and/or therapy with DDAVP.

scholarly journals Von Willebrand factor in patients on mechanical circulatory support – a double-edged sword between bleeding and thrombosis

2015 ◽  
Vol 3 ◽  
pp. 233-237 ◽  
Author(s):  
Bartosz Hudzik ◽  
Jacek Kaczmarski ◽  
Jerzy Pacholewicz ◽  
Michal Zakliczynski ◽  
Mariusz Gasior ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Mechanical Circulatory Support ◽  
Circulatory Support ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Clinical Significance of Inhibitors in Acquired von Willebrand Syndrome

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3623-3629
Author(s):  
Hiroshi Mohri ◽  
Shigeki Motomura ◽  
Heiwa Kanamori ◽  
Michio Matsuzaki ◽  
Shin-ichiro Watanabe ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Immunoglobulin Therapy ◽  
High Dose ◽  
Severe Bleeding ◽  
Bleeding Tendency ◽  
Intravenous Immunoglobulin Therapy ◽  
Acquired Von Willebrand Syndrome ◽  
Underlying Diseases ◽  
Von Willebrand ◽  
Willebrand Factor

Of 260 patients enrolled, 25 patients (9.6%) were associated with acquired von Willebrand syndrome (AvWS). We studied 25 patients with AvWS, retrospectively. AvWS was diagnosed by reduced levels of von Willebrand factor (vWF) (decrease of von Willebrand factor antigen [vWF:Ag] and von Willebrand ristocetin cofactor [vWF:RCoF]), a decrease of ristocetin-induced platelet agglutination (RIPA), sometimes decreased high-molecular-weight multimers, and prolonged bleeding time with neither prior nor family histories of bleeding problems and the evidence of normal vWF:RCoF in their families. The inhibitor of vWF was determined by mixing patient plasma with pooled normal plasma. Eight patients in this study had the inhibitors to vWF that were of the IgG class; the subclasses were IgG1 (7 cases) and IgG2 (1 case). Multimeric analysis of vWF showed selective loss of large multimers in most patients with AvWS similar to that of congenital type-2 von Willebrand disease (vWD). All inhibitors blocked ristocetin-mediated vWF binding to platelets. Five out of 6 IgGs evaluated here recognized the 39/34-kD fragment (residues 480/481-718) and Fragment III (residues 1-1365) that implied binding domain of glycoprotein Ib (GPIb), whereas 1 recognized Fragment I (residues 911-1365). A close relationship was found between the presence of the inhibitor and bleeding tendency. Of the 7 patients with inhibitors, 6 patients (86%) had a bleeding tendency, as well as 1 of the 15 patients without inhibitors (6%). The efficacy of treatment of underlying diseases and/or therapy with deamino D-arginine vasopressin (DDAVP) for the treatment of AvWS also depends on the presence of an inhibitor. Four of 8 patients with inhibitors (50%) had poor response to treatment of the underlying disease and/or therapy with DDAVP, as well as 1 of the 16 patients without inhibitors (6%). These results indicate that patients with AvWS developing inhibitors to vWF are likely to have bleeding problems and might be resistant to treatment of underlying diseases and/or therapy with DDAVP for bleeding to AvWS. We also showed evidence that intravenous immunoglobulin therapy (0.3 g/kg, 3 days) was effective to correct a hemostatic defect and manage severe bleeding in a patient with AvWS developing inhibitors. We might consider an additional treatment including expensive high-dose immunoglobulin therapy when uncontrollable bleeding is continued after the treatment of the underlying diseases and/or therapy with DDAVP.

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 Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support

2018 ◽  
Vol 71 (19) ◽  
pp. 2106-2118 ◽  
Author(s):  
Flavien Vincent ◽  
Antoine Rauch ◽  
Valentin Loobuyck ◽  
Emmanuel Robin ◽  
Christoph Nix ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Mechanical Circulatory Support ◽  
Circulatory Support ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow

Fluids ◽  
2021 ◽  
Vol 6 (2) ◽  
pp. 67
Author(s):  
Alireza Sharifi ◽  
David Bark
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Von Willebrand Factor ◽  
Circulatory Support ◽  
Acquired Von Willebrand Syndrome ◽  
Tensile Forces ◽  
Constant Shear Stress ◽  
Valve Diseases ◽  
Von Willebrand ◽  
Willebrand Factor

Von Willebrand factor (VWF) is a large multimeric hemostatic protein. VWF is critical in arresting platelets in regions of high shear stress found in blood circulation. Excessive cleavage of VWF that leads to reduced VWF multimer size in plasma can cause acquired von Willebrand syndrome, which is a bleeding disorder found in some heart valve diseases and in patients receiving mechanical circulatory support. It has been proposed that hemodynamics (blood flow) found in these environments ultimately leads to VWF cleavage. In the context of experiments reported in the literature, scission theory, developed for polymers, is applied here to provide insight into flow that can produce strong extensional forces on VWF that leads to domain unfolding and exposure of a cryptic site for cleavage through a metalloproteinase. Based on theoretical tensile forces, laminar flow only enables VWF cleavage when shear rate is large enough (>2800 s−1) or when VWF is exposed to constant shear stress for nonphysiological exposure times (>20 min). Predicted forces increase in turbulence, increasing the chance for VWF cleavage. These findings can be used when designing blood-contacting medical devices by providing hemodynamic limits to these devices that can otherwise lead to acquired von Willebrand syndrome.

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.

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