Response to “Parathyroid Adenoma in a Young Girl with Type 3 von Willebrand Disease”

We thank Dasdemir and Kaya for their letter[1] regarding our survey from the Italian Association of Hemophilia Centers on cancers in patients with congenital von Willebrand disease (VWD) published in Seminars in Thrombosis and Hemostasis.[2] The authors reported the case of a parathyroid adenoma in a 20-year-old woman with type 3 VWD. No similar cases were reported in our series of VWD patients.[2] However, the more important question is whether the association between this type (or other types) of tumor(s) and congenital VWD is incidental or if there is a causal association, based on the pathogenic role played by von Willebrand factor (VWF) in cancer cell biology.[3] [4] The issue is, however, restricted to the inherited forms of VWD, being well known that some types of tumors, especially hematological cancers, may cause acquired VWF defects.[5] There is growing body of evidence from experimental studies documenting significantly increased VWF plasma levels in a variety of cancer patient cohorts.[6] Such elevated VWF levels not only contribute to cancer-associated coagulopathy, in particular venous thromboembolism, but may also mediate cancer progression and metastasis. Studies have indeed shown that VWF can enhance expression of proinflammatory cytokines, regulate angiogenesis and vascular permeability, which in turn may facilitate tumor cell growth and extravasation across the vessel wall.[6] In this context, increased VWF levels appear to be a potent marker of advanced disease stage and worse prognosis. In keeping with these data, VWF inhibition results in metastasis attenuation.[7] The clinical correlation of these findings is, however, still unclear. It is indeed currently unknown if patients with a congenital qualitative or quantitative defect of VWF have an increased or, according to the above concepts more likely, a reduced predisposition to cancer development and/or progression than people without this hemorrhagic disorder. Unfortunately, epidemiological clinical data are lacking and the only published study is our survey documenting 106 cancers occurring in 92 VWD patients.[2]

Therefore, our conclusions remain the same of Dasdemir and Kaya[1]: additional data from studies or international registries are required and VWD patients should be closely followed for the possible onset of malignant diseases.

Publication History

Article published online:
09 February 2022

• References

• 1 Dasdemir S, Kaya Z. Parathyroid adenoma in a young girl with type 3 von Willebrand disease: comment on “Cancers in patients with von Willebrand disease”. Semin Thromb Hemost 2016; 42 (01) 36-41
• 2 Franchini M, Di Perna C, Santoro C. et al; Italian Association of Haemophilia Centres. Cancers in patients with von Willebrand disease: a survey from the Italian Association of Haemophilia Centres. Semin Thromb Hemost 2016; 42 (01) 36-41
• 3 O'Sullivan JM, Preston RJS, Robson T, O'Donnell JS. Emerging roles for von Willebrand factor in cancer cell biology. Semin Thromb Hemost 2018; 44 (02) 159-166
• 4 Franchini M, Frattini F, Crestani S, Bonfanti C, Lippi G. von Willebrand factor and cancer: a renewed interest. Thromb Res 2013; 131 (04) 290-292
• 5 Franchini M, Mannucci PM. Acquired von Willebrand syndrome: focused for hematologists. Haematologica 2020; 105 (08) 2032-2037
• 6 Patmore S, Dhami SPS, O'Sullivan JM. Von Willebrand factor and cancer; metastasis and coagulopathies. J Thromb Haemost 2020; 18 (10) 2444-2456
• 7 Karpatkin S, Pearlstein E, Ambrogio C, Coller BS. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest 1988; 81 (04) 1012-1019