Acquired von Willebrand syndrome in haematologic malignancies – how the clinical‐laboratory correlation improves a challenging diagnosis – a case series

Fidalgo, Teresa; Ferreira, Gisela; Oliveira, Alexandra; Pinto, Carla; Martinho, Patrícia; Mendes, Maria José; Duarte, Marta M.M.F.; Salvado, Ramón; Ribeiro, Maria Letı́cia

doi:10.1111/hae.13243

Cited by 3 publications

(4 citation statements)

References 10 publications

(28 reference statements)

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“…The immunochemotherapy used in some disseminated indolent lymphomas, such as bendamustine‐rituximab, CVP‐rituximab and CHOP‐rituximab was associated with AWS‐ORRs of 66.7% (4/6) 44–49 , 66.7% (2/3) 50,51 and 75% (3/4), respectively 44,46,52,53 . Older drugs, such as chlorambucil, provided an AWS‐ORR of 50% (2/4), 14,54,55 and more recent drugs, such as, showed an AWS‐ORR of 75% (3/4),47 , 51 including one inefficient combination with rituximab 47 .…”

Section: Resultsmentioning

confidence: 99%

Acquired von Willebrand syndrome and lymphoid neoplasms: A review of malignancy management, and propositions of practical recommendations

2022

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Introduction Acquired von Willebrand syndrome (AWS) is a rare and potentially life‐threatening bleeding disorder. AWS is primarily associated with lymphocyte‐related disorders (AWS‐LRD), such as lymphoma and IgM monoclonal gammopathy of undetermined significance (MGUS), and plasmocyte‐related disorders (AWS‐PRD), such as non‐IgM MGUS and myeloma. Symptomatic treatments are important to control and prevent bleeding, but AWS‐LRD and AWS‐PRD can only be cured by targeting the responsible clonal cell. No reviews exist on this specific subgroup of AWS. Aim We performed a literature review to help manage these rare cases. Method Thirty‐two AWS‐PRD and 43 AWS‐LRD cases with data on malignancy treatment were reported in 56 articles from the Medline database. Results LRDs were exclusively indolent and primarily associated with IgM monoclonal compounds. LRDs and PRDs may be treated because of severe bleeding symptoms, but severe VWF deficiency did not necessarily correlate with severe bleeding. Immunosuppressive drugs in AWS‐PRD, including rituximab, provided an overall response rate of AWS (AWS‐ORR) of 30% (3/10), including short responses. Anti‐myeloma drugs provided an AWS‐ORR of 71.4% (20/28), with long‐lasting remissions. Bortezomib was the most commonly used drug and provided an AWS‐ORR of 66.7% (6/9), including therapeutic associations with other anti‐myeloma drugs. Autologous and allogeneic stem cell transplantation was performed in eight and two patients, respectively, and some details on the management of AWS during these procedures were provided. Rituximab in AWS‐LRD provided an AWS‐ORR of 60% (3/5), and a chemotherapy + rituximab regimen increased the AWS‐ORR to above 50%. Bleeding syndrome in AWS‐PRD and AWS‐LRD generally improved prior to AWS biological improvement. Conclusion Long term remission of AWS due to lymphoid neoplasms is attainable by treating the underlying clonal cell. Some data and recommendations are provided to help answer difficult questions, including treatment timing, choice of drug, and the timing of evaluations and treatment changes.

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Section: Resultsmentioning

confidence: 99%

Acquired von Willebrand syndrome and lymphoid neoplasms: A review of malignancy management, and propositions of practical recommendations

2022

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“…Diagnosis of AVWS in the setting of hematological malignancies as WM is a rare and very challenging situation where an accurate clinical suspicion needs to be supported by a well-recommended laboratory workup that must include a VWF analysis. 1,[10][11][12] The ISTH (International Society of Haemostasis and Thrombosis) and others have provided recommendations for a laboratory workup algorithm where the screening tests should be followed by specific tests of VWF. It is important to perform laboratory workup based on this algorithm in order to detect AVWS that can be underdiagnosed in several hematological settings as well as to do a differential diagnosis of AVWS with inherited VWD.…”

Section: Discussionmentioning

confidence: 99%

<p>Good Profile of Efficacy/Tolerance of Bortezomib or Idelalisib in Waldenström Macroglobulinemia Associated with Acquired Von Willebrand Syndrome</p>

Ojeda-Uribe¹,

Rimelen²,

Marzullo³

2020

JBM

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Acquired von Willebrand syndrome (AVWS) in the setting of Waldenström macroglobulinemia (WM) is a challenging condition. No real standard of care is recommended for these patients, although the therapeutic strategy should include a rapid approach to the emergency bleeding events and to the underlying malignant lymphoid disorder. We report here our experience treating three elderly patients with these concomitant hematologic entities. The use of a bortezomib-based chemotherapy regimen showed a good profile of tolerance and efficacy even in a long-term follow-up period. These patients were treated for several years before switching their therapy to idelalisib, a targeted oral therapy that inhibits phosphatidylinositol 3-kinase isoform-delta (PI3KD), which is part of the signaling pathway downstream B-cell receptor. This approach was well tolerated and efficacious, although some adverse effects were observed, particularly at hepatic levels, but were all reversible. The same profile of tolerance/efficacy was observed in one very old patient who received idelalisib as a first-line therapy. We think that bortezomib-based therapy could be considered in refractory patients with AVWS associated with WM.

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“…Additional lymphoproliferative disorders have been described, including Waldenstrom’s macroglobulinemia (WM) which responded to chemotherapy and plasmapheresis, and marginal zone lymphoma, which responds to chemotherapy 91. In WM, the IgM paraprotein binds VWF and clears it from circulation.…”

Section: Acquired Avws and Agingmentioning

confidence: 99%

“…In essential thrombocythemia, characterized by an excess of platelets, high molecular weight multimers (HMWM) adsorb onto the surface of activated platelets removing VWF from circulation. Cytoreduction with hydroxyurea has been shown to reverse this deficit in some cases 91. Chronic myeloid leukemia has also been associated with AVWS and loss of HMWMs.…”

Section: Acquired Avws and Agingmentioning

confidence: 99%

Von Willebrand Disease in the elderly: clinical perspectives

Chapin

2018

CIA

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Von Willebrand disease (VWD) is an inherited bleeding disorder that affects up to 1% of the population. In most cases, VWD results from a mutation in the von Willebrand Factor (VWF) gene, which alters the amount and function of VWF, a key glycoprotein in both primary and secondary hemostasis. A comprehensive analysis of patients with VWD should include VWF activity, antigen levels, platelet function, and a careful bleeding history. Treatment options include antifibrinolytics, desmopressin, and VWF replacement therapy. VWF levels fluctuate due to age, stress, environmental exposures, and pharmacologic treatment. Treatment guidelines exist to treat and prevent bleeding for patients undergoing surgery and medical procedures, but often these must be reevaluated in the setting of age-related comorbidities including cardiovascular events, venous thrombosis, and malignancy. In addition, many age-related complications are associated with a secondary acquired von Willebrand syndrome (AVWS), including malignancies, hypothyroidism, cardiovascular diseases, and cardiac replacement devices. The current literature is limited by a lack of older patients in clinical trials. Larger studies are needed to determine if age-related comorbidities affect VWD patients at different frequencies than the general elderly population. There is also a significant need for registry-based studies to evaluate many age-related comorbidities in VWD patients.

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Acquired von Willebrand syndrome in haematologic malignancies – how the clinical‐laboratory correlation improves a challenging diagnosis – a case series

Cited by 3 publications

References 10 publications

Acquired von Willebrand syndrome and lymphoid neoplasms: A review of malignancy management, and propositions of practical recommendations

Acquired von Willebrand syndrome and lymphoid neoplasms: A review of malignancy management, and propositions of practical recommendations

<p>Good Profile of Efficacy/Tolerance of Bortezomib or Idelalisib in Waldenström Macroglobulinemia Associated with Acquired Von Willebrand Syndrome</p>

Von Willebrand Disease in the elderly: clinical perspectives

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