Why is Misdiagnosis of von Willebrand Disease Still Prevalent and How Can We Overcome It? A Focus on Clinical Considerations and Recommendations

References

• Bowman M, Hopman WM, Rapson D, Lillicrap D, James P. The prevalence of symptomatic von Willebrand disease in primary care practice. J Thromb Haemost. 2010;8(1):213–216. Epub 2009 Oct 23. PMID: 19874468. doi:10.1111/j.1538-7836.2009.03661
   PubMed Web of Science ®Google Scholar
• Lavin M, O’Donnell JS. How I treat low von Willebrand factor levels. Blood. 2019;133(8):795–804. Epub 2018 Dec 21. PMID: 30578256. doi:10.1182/blood-2018-10-844936
   PubMed Web of Science ®Google Scholar
• von Willebrand EA. Hereditar pseudohemofili. Fin Laekaresaellsk Hand. 1926;68:87–112.
   Google Scholar
• Sadler JE, Budde U, Eikenboom JC, et al.; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the subcommittee on von Willebrand factor. J Thromb Haemost. 2006;4(10):2103–2114. Epub 2006 Aug 2. PMID: 16889557. doi:10.1111/j.1538-7836.2006.02146.x
   PubMed Web of Science ®Google Scholar
• Favaloro EJ. Diagnosing von Willebrand disease: a short history of laboratory milestones and innovations, plus current status, challenges, and solutions. Semin Thromb Hemost. 2014;40(5):551–570. Epub 2014 Jun 30. PMID: 24978322. doi:10.1055/s-0034-1383546
   PubMed Web of Science ®Google Scholar
• Favaloro EJ, Pasalic L, Curnow J. Laboratory tests used to help diagnose von Willebrand disease: an update. Pathology. 2016;48(4):303–318. Epub 2016 May 4. PMID: 27131932. doi:10.1016/j.pathol.2016.03.001
   PubMed Web of Science ®Google Scholar
• Lillicrap D. von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy. Blood. 2013;122(23):3735–3740. Epub 2013 Sep 24. PMID: 24065240; PMCID: PMC3952678. doi:10.1182/blood-2013-06-498303
   PubMed Web of Science ®Google Scholar
• Ng C, Motto DG, Di Paola J. Diagnostic approach to von Willebrand disease. Blood. 2015;125(13):2029–2037. Epub 2015 Feb 23. PMID: 25712990; PMCID: PMC4375103. doi:10.1182/blood-2014-08-528398
   PubMed Web of Science ®Google Scholar
• De Jong A, Eikenboom J. Developments in the diagnostic procedures for von Willebrand disease. J Thromb Haemost. 2016;14(3):449–460. Epub 2016 Feb 12. PMID: 26714181. doi:10.1111/jth.13243
   PubMed Web of Science ®Google Scholar
• Bolton-Maggs PH, Lillicrap D, Goudemand J, Berntorp E. von Willebrand disease update: diagnostic and treatment dilemmas. Haemophilia. 2008;14(Suppl s3):56–61. PMID: 18510523. doi:10.1111/j.1365-2516.2008.01713.x
   Web of Science ®Google Scholar
• Siboni S, Biguzzi E, Caiani V, Mistretta C, Bucciarelli P, Peyvandi F. Baseline factor VIII plasma levels and age at first bleeding in patients with severe forms of von Willebrand disease. Haemophilia. 2016;22(4):564–569. doi:10.1111/hae.12900
   PubMed Web of Science ®Google Scholar
• Sanders YV, Giezenaar MA, Laros-van Gorkom BA, et al.; WiN study group. von Willebrand disease and aging: an evolving phenotype. J Thromb Haemost. 2014;12(7):1066–1075. PMID: 24750783. doi:10.1111/jth.12586
   PubMed Web of Science ®Google Scholar
• Rodeghiero F, Tosetto A, Abshire T, et al.; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost. 2010;8(9):2063–2065. PMID: 20626619. doi:10.1111/j.1538-7836.2010.03975.x
   PubMed Web of Science ®Google Scholar
• Abebe W. Review of herbal medications with the potential to cause bleeding: dental implications, and risk prediction and prevention avenues. EPMA J. 2019;10(1):51–64. PMID: 30984314; PMCID: PMC6459456. doi:10.1007/s13167-018-0158-2
   PubMed Web of Science ®Google Scholar
• Castaman G, Montgomery RR, Meschengieser SS, Haberichter SL, Woods AI, Lazzari MA. von Willebrand’s disease diagnosis and laboratory issues. Haemophilia. 2010;16 Suppl 5(5):67–73. PMID: 20590859; PMCID: PMC4313748. doi:10.1111/j.1365-2516.2010.02296.x
   Web of Science ®Google Scholar
• James PD, Connell NT, Ameer B, et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv. 2021;5(1):280–300. PMID: 33570651; PMCID: PMC7805340. doi:10.1182/bloodadvances.2020003265
   PubMed Web of Science ®Google Scholar
• Sharma R, Haberichter SL. New advances in the diagnosis of von Willebrand disease. Hematology Am Soc Hematol Educ Program. 2019;2019(1):596–600. PMID: 31808831; PMCID: PMC6913428. doi:10.1182/hematology.2019000064
   Google Scholar
• Sztukowska M, Gallinaro L, Cattini MG, et al. Von Willebrand factor propeptide makes it easy to identify the shorter Von Willebrand factor survival in patients with type 1 and type Vicenza von Willebrand disease. Br J Haematol. 2008;143(1):107–114. Epub 2008 Aug 7. PMID: 18691167. doi:10.1111/j.1365-2141.2008.07311.x
   Web of Science ®Google Scholar
• Haberichter SL, Castaman G, Budde U, et al. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD). Blood. 2008;111(10):4979–4985. Epub 2008 Mar 14. PMID: 18344424; PMCID: PMC2384129. doi:10.1182/blood-2007-09-110940
   Web of Science ®Google Scholar
• Koutts J. A short history of diagnostic tests for von Willebrand disease: in memory of Barry Firkin (1930 to 2001) and Ted Zimmerman (1937 to 1988). Semin Thromb Hemost. 2006;32(5):445–455. PMID: 16862517. doi:10.1055/s-2006-947858
   Web of Science ®Google Scholar
• Sadler JE. Von Willebrand disease type 1: a diagnosis in search of a disease. Blood. 2003;101(6):2089–2093. Epub 2002 Oct 31. PMID: 12411289. doi:10.1182/blood-2002-09-2892
   PubMed Web of Science ®Google Scholar
• Favaloro EJ, Lippi G. Preanalytical issues that may cause misdiagnosis in haemophilia and von Willebrand disease. Haemophilia. 2018;24(2):198–210. Epub 2017 Dec 22. PMID: 29271545. doi:10.1111/hae.13396
   PubMed Web of Science ®Google Scholar
• Brodersen J, Schwartz LM, Heneghan C, O’Sullivan JW, Aronson JK, Woloshin S. Overdiagnosis: what it is and what it isn’t. BMJ Evid Based Med. 2018;23(1):1–3. PMID: 29367314. doi:10.1136/ebmed-2017-110886
   PubMedGoogle Scholar
• Magnette A, Chatelain M, Chatelain B, Ten Cate H, Mullier F. Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories. Thromb J. 2016;14(1):49. PMID: 27999475; PMCID: PMC5154122. doi:10.1186/s12959-016-0123-z
   Google Scholar
• Lippi G, Maffulli N. Biological influence of physical exercise on hemostasis. Semin Thromb Hemost. 2009;35(3):269–276. Epub 2009 May 18. PMID: 19452402. doi:10.1055/s-0029-1222605
   PubMed Web of Science ®Google Scholar
• Brenner B. Haemostatic changes in pregnancy. Thromb Res. 2004;114(5–6):409–414. PMID: 15507271. doi:10.1016/j.thromres.2004.08.004
   PubMed Web of Science ®Google Scholar
• Kouides PA, Conard J, Peyvandi F, Lukes A, Kadir R. Hemostasis and menstruation: appropriate investigation for underlying disorders of hemostasis in women with excessive menstrual bleeding. Fertil Steril. 2005;84(5):1345–1351. PMID: 16275228. doi:10.1016/j.fertnstert.2005.05.035
   PubMed Web of Science ®Google Scholar
• Favaloro EJ, Soltani S, McDonald J, Grezchnik E, Easton L, Favaloro JW. Reassessment of ABO blood group, sex, and age on laboratory parameters used to diagnose von Willebrand disorder: potential influence on the diagnosis vs the potential association with risk of thrombosis. Am J Clin Pathol. 2005;124(6):910–917. Erratum in: Am J Clin Pathol. 2006 May;125(5):796.PMID: 16416741. doi:10.1309/W76QF806CE80CL2T
   Web of Science ®Google Scholar
• Favaloro EJ, Bonar RA, Meiring M, et al. Evaluating errors in the laboratory identification of von Willebrand disease in the real world. Thromb Res. 2014;134(2):393–403. Epub 2014 May 21. PMID: 24913998. doi:10.1016/j.thromres.2014.05.020
   Web of Science ®Google Scholar
• Chandler WL, Peerschke EI, Castellone DD, Meijer P; NASCOLA Proficiency Testing Committee. Von Willebrand factor assay proficiency testing. The North American specialized coagulation laboratory association experience. Am J Clin Pathol. 2011;135(6):862–869. PMID: 21571959. doi:10.1309/AJCPH5JK4ONENPAE
   Web of Science ®Google Scholar
• Verfaillie CJ, De Witte E, Devreese KM. Validation of a new panel of automated chemiluminescence assays for von Willebrand factor antigen and activity in the screening for von Willebrand disease. Int J Lab Hematol. 2013;35(5):555–565. Epub 2013 Apr 3. PMID: 23551532. doi:10.1111/ijlh.12087
   Web of Science ®Google Scholar
• Cabrera N, Moret A, Caunedo P, et al. Comparison of a new chemiluminescent immunoassay for von Willebrand factor activity with the ristocetin cofactor-induced platelet agglutination method. Haemophilia. 2013;19(6):920–925. Epub 2013 Jun 4. PMID: 23730809. doi:10.1111/hae.12203
   Web of Science ®Google Scholar
• de Maistre E, Volot F, Mourey G, et al. Performance of two new automated assays for measuring von Willebrand activity: hemosIL AcuStar and innovance. Thromb Haemost. 2014;112(4):825–830. Epub 2014 Aug 7. PMID: 25103956. doi:10.1160/TH14-02-0108
   Web of Science ®Google Scholar
• Tiede A, Rand JH, Budde U, Ganser A, Federici AB. How I treat the acquired von Willebrand syndrome. Blood. 2011;117(25):6777–6785. Epub 2011 May 3. PMID: 21540459. doi:10.1182/blood-2010-11-297580
   PubMed Web of Science ®Google Scholar
• Shetty S, Kasatkar P, Ghosh K. Pathophysiology of acquired von Willebrand disease: a concise review. Eur J Haematol. 2011;87(2):99–106. PMID: 21535159. doi:10.1111/j.1600-0609.2011.01636.x
   Web of Science ®Google Scholar