Acquired von Willebrand syndrome: von Willebrand factor propeptide to von Willebrand factor antigen ratio predicts remission status

Lee, Adrienne; Sinclair, Gary D.; Valentine, Karen; James, Paula D.; Poon, Man‐Chiu

doi:10.1182/blood-2014-02-557132

Cited by 10 publications

(9 citation statements)

References 21 publications

(17 reference statements)

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“…By following up the patient over time, a decrease in the VWFpp/VWF:Ag was observed, along with the normalization of VWF measurements that occurred one month after the beginning of the immunosuppressive therapy. The baseline results of the VWFpp/VWF:Ag measurement facilitated the differential diagnosis between VWD and AVWS, and evaluation over time confirmed the efficacy of the immunological treatment and the remission of the underlying disease, previously undiagnosed 12. It has been already reported that the eradication of the autoantibodies with an aggressive immunosuppression therapy is critical for the treatment of underlying autoimmune disorders, 1 as confirmed herewith.…”

supporting

confidence: 76%

Severe acquired von Willebrand syndrome secondary to systemic lupus erythematosus

et al. 2018

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supporting

confidence: 76%

Severe acquired von Willebrand syndrome secondary to systemic lupus erythematosus

et al. 2018

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“…after administration of VWF concentrate. The presence of anti-VWF antibodies is confirmed by VWFpp and VWFpp/ /VWF: Ag ratio [53].…”

Section: Discussionmentioning

confidence: 87%

“…In 2014, Lee et al [53] described changes in VWFpp/VWF: Ag ratio during the course of treatment of a patient with anti-VWF inhibitor antibodies. At first diagnosis, VWF: RCo, VWF: Ag ratio and FVIII were indeterminate, VWFpp/ /VWF: Ag ratio markedly increased.…”

Section: Discussionmentioning

confidence: 99%

“…Differences in VWFpp and VWF half-life that reflect the clearance rate of VWF from plasma have been used in diagnostics of VWD [24-27, 30, 51] and AVWS [52][53][54][55]. VWFpp concentration, the VWFpp/ /VWF: Ag ratio as well as the VIII: C/VWF: Ag ratio are already recognized biomarkers of VWF synthesis, release and clearance [47,56].…”

Section: Von Willebrand Factor Propetidementioning

confidence: 99%

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Von Willebrand factor propeptide (VWFpp) — potential biomarker in inherited von Willebrand disease and acquired von Willebrand syndrome

Bykowska

Ceglarek²,

Gwozdowska³

et al. 2019

Journal of Transfusion Medicine

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Von Willebrand factor propeptide (VWFpp) is a fragment of a new synthesized VWF molecule that plays an important part in the biosynthesis of this protein. After completion of multimerisation of von Willebrand factor (VWF) dimers in the Golgi apparatus, as result of furin proteolysis VWFpp is truncated/disconnected from the mature VWF molecule to form a non-covalent complex with VWF. The VWFpp-VWF complex is stored in endothelial and platelet storage granules and released into the bloodstream where it dissociates into VWFpp and VWF. Plasma VWFpp level and ratio of plasma VWF propeptide (VWFpp) to VWF antigen (VWF:Ag) i.e VWFpp /VWF:Ag ratio are important biomarkers of VWF synthesis/release/clearance. These biomarkers have distinct therapeutic utility as they help to identify patients with von Willebrand disease (VWD) in whom DDAVP (desmopressin 1-desamino-8-D-arginine vasopressin) is ineffective due to rapid VWF clearance. They also have significant diagnostic value because they help to differentiate between congenital VWD subtypes as well as between congenital VWD and acquired von Willebrand Syndrome (AVWS). The purpose of the study was to determine the VWFpp level and the VWFpp/VWF: Ag ratio in patients with VWD and AVWS and to assess the significance of these biomarkers for diagnosis and management of congenital and acquired von Willebrand disease. Our study involved 120 VWD patients; 21 with AVWS and 111 healthy controls. Study results confirm that VWFpp level and the VWFpp/VWF: Ag ratio have significant value for discrimination between severe type 1 VWD and type 3 VWD as well as between acquired and congenital VWD which has serious implications for therapy. The biomarkers are also useful for identification of patients in whom DDAVP treatment may prove ineffective. In type 1 VWD (< 30 IU/ml) the VWFpp/VWF: Ag ratio was elevated in 57% of patients while in the group of patients with threshold VWF values ('Low VWF', 30-50 IU/dL) the ratio was within normal, which may be suggestive of other underlying causes of VWF deficiency. Assays in patients with non-neutralizing anti-VWF antibodies (AVWS) have shown that the VWFpp/VWF: Ag ratio www.jtm.viamedica.pl Ksenia Bykowska et al., Von Willebrand factor propeptide (VWFpp) can have significant impact on monitoring therapy and assessment of remission in patients with anti VWF antibodies.

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“…VWFpp is cleaved in the trans-Golgi but remains stored together with mature VWF in platelet α-granules and endothelial cell Weibel-Palade bodies in equimolar amounts. After release, VWFpp dissociates from the mature VWF subunit, circulates with a steady-state half-life, and serves as a marker of VWF secretion 10. A high VWF:pp/Ag ratio has been proposed by Scott et al,11 as a simple method to distinguish AVWS due to decreased VWF synthesis from that due to increased clearance.…”

Section: Discussionmentioning

confidence: 99%

Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

Qamar

Lee²,

Valentine³

et al. 2017

Mediterr J Hematol Infect Dis

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Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

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Acquired von Willebrand syndrome: von Willebrand factor propeptide to von Willebrand factor antigen ratio predicts remission status

Abstract: Key Points• Remission status in relapsingremitting AVWS depends on the balance of VWF clearance by anti-VWF antibody and VWF secretion.

Cited by 10 publications

References 21 publications

Severe acquired von Willebrand syndrome secondary to systemic lupus erythematosus

Severe acquired von Willebrand syndrome secondary to systemic lupus erythematosus

Von Willebrand factor propeptide (VWFpp) — potential biomarker in inherited von Willebrand disease and acquired von Willebrand syndrome

Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

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