377
Views
1
CrossRef citations to date
0
Altmetric
Review

The diagnosis, natural history, and management of von Willebrand disease in women in the age of guidelines

ORCID Icon & ORCID Icon
Pages 435-450 | Received 21 Aug 2022, Accepted 06 Jan 2023, Published online: 12 Jan 2023

References

  • Zia A, Jain S, Kouides P, et al. Bleeding disorders in adolescents with heavy menstrual bleeding in a multicenter prospective US cohort. Haematologica. 2020;105(7):1969–1976.
  • Hawke L, Grabell J, Sim W, et al. Obstetric bleeding among women with inherited bleeding disorders: a retrospective study. Haemoph Off J World Fed Hemoph. 2016;22(6):906–911.
  • Shankar M, Lee CA, Sabin CA, et al. von Willebrand disease in women with menorrhagia: a systematic review. BJOG Int J Obstet Gynaecol. 2004;111(7):734–740.
  • Laffan M, Sathar J, Johnsen JM. von Willebrand disease: diagnosis and treatment, treatment of women, and genomic approach to diagnosis. Haemoph Off J World Fed Hemoph. 2021;27(Suppl 3):66–74.
  • Swaminathan N, Sharathkumar A, Dowlut-McElroy T. Reproductive tract bleeding in adolescent and young adult females with inherited bleeding disorders: an underappreciated problem. J Pediatr Adolesc Gynecol. 2022;35(6):614–623.
  • James AH, Myers ER, Cook C, et al. Complications of hysterectomy in women with von Willebrand disease. Haemoph Off J World Fed Hemoph. 2009;15(4):926–931.
  • Zia A, Lau M, Journeycake J, et al. Developing a multidisciplinary young women’s blood disorders program: a single-centre approach with guidance for other centres. Haemoph Off J World Fed Hemoph. 2016;22(2):199–207.
  • Johnson S, Lang A, Sturm M, et al. Iron deficiency without anemia: a common yet under-recognized diagnosis in young women with heavy menstrual bleeding. J Pediatr Adolesc Gynecol. 2016;29(6):628–631.
  • Byrne B, Ryan K, Lavin M. Current challenges in the peripartum management of women with Von Willebrand disease. Semin Thromb Hemost. 2021;47(2):217–228.
  • Werner EJ, Broxson EH, Tucker EL, et al. Prevalence of von Willebrand disease in children: a multiethnic study. J Pediatr. 1993;123(6):893–898.
  • Bowman M, Hopman WM, Rapson D, et al. The prevalence of symptomatic von Willebrand disease in primary care practice. J Thromb Haemost JTH. 2010;8(1):213–216.
  • Haley KM, Sidonio RF, Abraham S, et al. A cross-sectional study of women and girls with congenital bleeding disorders: the American thrombosis and hemostasis network cohort. J Womens Health. 2020;29(5):670–676.
  • Zia A, Stanek J, Christian-Rancy M, et al. Utility of a screening tool for haemostatic defects in a multicentre cohort of adolescents with heavy menstrual bleeding. Haemoph Off J World Fed Hemoph. 2018;24(6):957–963.
  • Philipp CS, Faiz A, Heit JA, et al. Evaluation of a screening tool for bleeding disorders in a US multisite cohort of women with menorrhagia. Am J Obstet Gynecol. 2011;204(3):209.e1–7.
  • Von Willebrand Disease in Women. [cited 2022 Aug 18]. Available from: https://www.acog.org/en/clinical/clinical-guidance/committee-opinion/articles/2013/12/von-willebrand-disease-in-women.
  • Connell NT, Flood VH, Brignardello-Petersen R, et al., ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv. 2021;5(1):301–325.
  • Higham JM, O’Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990;97(8):734–739.
  • Zakherah MS, Sayed GH, El-Nashar SA, et al. Pictorial blood loss assessment chart in the evaluation of heavy menstrual bleeding: diagnostic accuracy compared to alkaline hematin. Gynecol Obstet Invest. 2011;71(4):281–284.
  • Kadir RA, Economides DL, Sabin CA, et al. Assessment of menstrual blood loss and gynaecological problems in patients with inherited bleeding disorders. Haemoph Off J World Fed Hemoph. 1999;5(1):40–48.
  • Jacobson AE, Vesely SK, Koch T, et al. Patterns of von Willebrand disease screening in girls and adolescents with heavy menstrual bleeding. Obstet Gynecol. 2018;131(6):1121–1129.
  • Punt MC, Waning ML, Mauser-Bunschoten EP, et al. Maternal and neonatal bleeding complications in relation to peripartum management in women with Von Willebrand disease: a systematic review. Blood Rev. 2020;39:100633.
  • Veen CSB, van der Reijken IS, Jansen AJG, et al. Severe postpartum haemorrhage as first presenting symptom of an inherited bleeding disorder. Haemoph Off J World Fed Hemoph. 2019;25(6):1051–1058.
  • Srivaths L, Minard CG, O’Brien SH, et al. The spectrum and severity of bleeding in adolescents with low von Willebrand factor-associated heavy menstrual bleeding. Blood Adv. 2020;4(13):3209–3216.
  • Srivaths LV, Zhang QC, Byams VR, et al. Differences in bleeding phenotype and provider interventions in postmenarchal adolescents when compared to adult women with bleeding disorders and heavy menstrual bleeding. Haemoph Off J World Fed Hemoph. 2018;24(1):63–69.
  • Halterman JS, Kaczorowski JM, Aligne CA, et al. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics. 2001;107(6):1381–1386.
  • Bruner AB, Joffe A, Duggan AK, et al. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet Lond Engl. 1996;348(9033):992–996.
  • Parker M, Hannah M, Zia A. “If I wasn’t a girl”: experiences of adolescent girls with heavy menstrual bleeding and inherited bleeding disorders. Res Pract Thromb Haemost. 2022;6(4):e12727.
  • Weyand AC, Fitzgerald KD, McGrath M, et al. Depression in female adolescents with heavy menstrual bleeding. J Pediatr. 2022;240:171–176.
  • Lavin M, Aguila S, Dalton N, et al., Significant gynecological bleeding in women with low von Willebrand factor levels. Blood Adv. 2018;2(14):1784–1791.
  • 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.
  • James AH. More than menorrhagia: a review of the obstetric and gynaecological manifestations of bleeding disorders. Haemoph Off J World Fed Hemoph. 2005;11(4):295–307.
  • Kirtava A, Drews C, Lally C, et al. Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand’s disease receiving care in haemophilia treatment centres: a case-control study. Haemoph Off J World Fed Hemoph. 2003;9(3):292–297.
  • Borzutzky C, Jaffray J. Diagnosis and management of heavy menstrual bleeding and bleeding disorders in adolescents. JAMA Pediatr. 2020;174(2):186–194.
  • Baronciani L, Peyvandi F. How we make an accurate diagnosis of von Willebrand disease. Thromb Res. 2020;196:579–589.
  • Jain S, Zhang S, Acosta M, et al. Prospective evaluation of ISTH-BAT as a predictor of bleeding disorder in adolescents presenting with heavy menstrual bleeding in a multidisciplinary hematology clinic. J Thromb Haemost JTH. 2020;18(10):2542–2550.
  • Lavin M, Christopherson P, Grabell J, et al. Longitudinal bleeding assessment in von Willebrand disease utilizing an interim bleeding score. J Thromb Haemost JTH. 2022;20(10):2246–2254.
  • Nichols WL, Hultin MB, James AH, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) expert panel report (USA). Haemoph Off J World Fed Hemoph. 2008;14:171–232.
  • Cheves TA, DeMarinis S, Sweeney JD. Laboratory methods in the assessment of hereditary hemostatic disorders. Hematol Oncol Clin North Am. 2021;35(6):1051–1068.
  • Seidizadeh O, Peyvandi F, Mannucci PM. Von Willebrand disease type 2N: an update. J Thromb Haemost JTH. 2021;19(4):909–916.
  • Favaloro EJ. Commentary on the ASH ISTH NHF WFH 2021 guidelines on the diagnosis of VWD: reflections based on recent contemporary test data. Blood Adv. 2022;6(2):416–419.
  • Miller CH, Dilley AB, Drews C, et al. Changes in von Willebrand factor and factor VIII levels during the menstrual cycle. Thromb Haemost. 2002;87(6):1082–1083.
  • Kadir RA, Economides DL, Sabin CA, et al. Variations in coagulation factors in women: effects of age, ethnicity, menstrual cycle and combined oral contraceptive. Thromb Haemost. 1999;82(11):1456–1461.
  • Alperin JB. Estrogens and surgery in women with von Willebrand’s disease. Am J Med. 1982;73(3):367–371.
  • Sadler B, Castaman G, O’Donnell JS. von Willebrand disease and von Willebrand factor. Haemoph Off J World Fed Hemoph. 2022;28(Suppl 4):11–17.
  • Jaffray J, Staber JM, Malvar J, et al. Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: a multi-center study. Am J Hematol. 2020;95(9):1022–1029.
  • Brown MC, White MH, Friedberg R, et al. Elevated von Willebrand factor levels during heavy menstrual bleeding episodes limit the diagnostic utility for von Willebrand disease. Res Pract Thromb Haemost. 2021;5(4):e12513.
  • Seaman CD, Ragni MV. The effect of age on von Willebrand factor and bleeding symptoms in von Willebrand disease. Thromb Haemost. 2020;120(8):1159–1165.
  • Abou-Ismail MY, Ogunbayo GO, Secic M, et al., Outgrowing the laboratory diagnosis of type 1 von Willebrand disease: a two decade study. Am J Hematol. 2018;93(2):232–237.
  • Brignardello-Petersen R, El Alayli A, Husainat N, et al., Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature. Blood Adv. 2022;6(1):228–237.
  • Qiu J, Cheng J, Wang Q, et al. Levonorgestrel-releasing intrauterine system versus medical therapy for menorrhagia: a systematic review and meta-analysis. Med Sci Monit Int Med J Exp Clin Res. 2014;20:1700–1713.
  • Chi C, Huq FY, Kadir RA. Levonorgestrel-releasing intrauterine system for the management of heavy menstrual bleeding in women with inherited bleeding disorders: long-term follow-up. Contraception. 2011;83(3):242–247.
  • Huguelet PS, Laurin JL, Thornhill D, et al. Use of the levonorgestrel intrauterine system to treat heavy menstrual bleeding in adolescents and young adults with inherited bleeding disorders and Ehlers-danlos syndrome. J Pediatr Adolesc Gynecol. 2022;35(147–152.e1):147–152.e1.
  • Rimmer E, Jamieson MA, James P. Malposition and expulsion of the levonorgestrel intrauterine system among women with inherited bleeding disorders. Haemoph Off J World Fed Hemoph. 2013;19(6):933–938.
  • O’Flynn O’Brien KL, Wheeler AP, Borzutzky C, et al. Provider attitudes and practices regarding Intrauterine System (IUS) insertion in adolescents with and without bleeding disorders for management of heavy menstrual bleeding. J Pediatr Adolesc Gynecol. 2021;34(4):514–521.
  • Khalighi M, Wheeler AP, Adeyemi-Fowode OA, et al. Does a bleeding disorder lessen the efficacy of the 52-mg levonorgestrel-releasing intrauterine system for heavy menstrual bleeding in adolescents? A retrospective multicenter study. J Adolesc Health Off Publ Soc Adolesc Med. 2022;71(2):204–209.
  • Leebeek FWG, How AF. I manage severe von Willebrand disease. Br J Haematol. 2019;187(4):418–430.
  • Kadir RA, Lee CA, Sabin CA, et al. DDAVP nasal spray for treatment of menorrhagia in women with inherited bleeding disorders: a randomized placebo-controlled crossover study. Haemoph Off J World Fed Hemoph. 2002;8(6):787–793.
  • Edlund M, Blombäck M, Fried G. Desmopressin in the treatment of menorrhagia in women with no common coagulation factor deficiency but with prolonged bleeding time. Blood Coagul Fibrinolysis Int J Haemost Thromb. 2002;13(3):225–231.
  • Kouides PA, Byams VR, Philipp CS, et al. Multisite management study of menorrhagia with abnormal laboratory haemostasis: a prospective crossover study of intranasal desmopressin and oral tranexamic acid. Br J Haematol. 2009;145(2):212–220.
  • Srivaths LV, Dietrich JE, Yee DL, et al. Oral tranexamic acid versus combined oral contraceptives for adolescent heavy menstrual bleeding: a pilot study. J Pediatr Adolesc Gynecol. 2015;28(4):254–257.
  • Ragni MV, Machin N, Malec LM, et al. Von Willebrand factor for menorrhagia: a survey and literature review. Haemoph Off J World Fed Hemoph. 2016;22(3):397–402.
  • Mannucci PM. New therapies for von Willebrand disease. Blood Adv. 2019;3(21):3481–3487.
  • Greenmyer JR, Burd L, Kobrinsky NL. Octreotide for the treatment of abnormal uterine bleeding in women with bleeding and clotting disorders. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet. 2021;153(1):171–174.
  • Committee on Adolescent Health Care, Committee on Gynecologic Practice. Committee opinion No.580: von Willebrand disease in women. Obstet Gynecol. 2013;122(6):1368–1373.
  • Clark P. Changes of hemostasis variables during pregnancy. Semin Vasc Med. 2003;3(1):13–24.
  • James AH, Konkle BA, Kouides P, et al., Postpartum von Willebrand factor levels in women with and without von Willebrand disease and implications for prophylaxis. Haemoph Off J World Fed Hemoph. 2015;21(1):81–87.
  • Ahmadzia HK, Phillips JM, James AH, et al. Predicting peripartum blood transfusion in women undergoing cesarean delivery: a risk prediction model. PloS One. 2018;13(1):e0208417.
  • Stoof SCM, van Steenbergen HW, Zwagemaker A, et al. Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: a retrospective survey. Haemoph Off J World Fed Hemoph. 2015;21(4):505–512.
  • Ragni MV, Machin N, James AH, et al. Feasibility of the Von Willebrand disease PREVENT trial. Thromb Res. 2017;156:8–13.
  • Kouides PA. Preventing postpartum haemorrhage-when guidelines fall short. Haemoph Off J World Fed Hemoph. 2015;21(4):502–504.
  • Ragni MV. Blood volume-based von Willebrand factor to prevent postpartum hemorrhage in von Willebrand disease. Blood Adv. 2017;1(11):703–706.
  • Machin N, Ragni MV. Recombinant vs plasma-derived von Willebrand factor to prevent postpartum hemorrhage in von Willebrand disease. Blood Adv. 2020;4(14):3234–3238.
  • Pavord S, Rayment R, Madan B, etal. Management of inherited bleeding disorders in pregnancy: green-top guideline No. 71 (joint with UKHCDO). BJOG Int J Obstet Gynaecol. 2017;124:e193–e263.
  • Reale SC, Farber MK, Lumbreras-Marquez MI, et al. Anesthetic management of Von Willebrand disease in pregnancy: a retrospective analysis of a large case series. Anesth Analg. 2021;133(5):1244–1250.
  • Hibbs SP, Roberts I, Shakur-Still H, et al., Post-partum haemorrhage and tranexamic acid: a global issue. Br J Haematol. 2018;180(6):799–807.
  • Ahmadzia HK, Luban NLC, Li S, et al. Optimal use of intravenous tranexamic acid for hemorrhage prevention in pregnant women. Am J Obstet Gynecol. 2021;225(1):85.e1–85.e11.
  • Prevention and management of postpartum haemorrhage: green-top guideline No. 52. BJOG Int J Obstet Gynaecol. 2017;124(5):e106–e149.
  • Demers C, Derzko C, David M, et al. No. 163-gynaecological and obstetric management of women with inherited bleeding disorders. J Obstet Gynaecol Can. 2018;40(2):e91–e103.
  • Makhamreh MM, Russo ML, Karl T, et al. Type 2B von Willebrand disease in pregnancy: a systematic literature review. Semin Thromb Hemost. 2021;47(2):201–216.
  • Turan O, Kadir RA. Pregnancy in special populations: challenges and solutions practical aspects of managing von Willebrand disease in pregnancy. Hematol Am Soc Hematol Educ Program. 2021;2021(1):552–558.
  • CDC. Data and statistics on von Willebrand disease | CDC [Internet]. Cent Dis Control Prev. 2020. cited 2022 Aug 13 Available from https://www.cdc.gov/ncbddd/vwd/data.html
  • Konkle BA. Progress toward meeting the needs of adolescent females with bleeding disorders. Haemoph Off J World Fed Hemoph. 2016;22(2):196–198.
  • Weyand AC, James PD. Sexism in the management of bleeding disorders. Res Pract Thromb Haemost. 2021;5(1):51–54.
  • Sholzberg M, James PD. Commentary: surviving sexism in bleeding disorders affecting women. Br J Haematol. 2022;196(1):15–16.
  • van Galen K, Lavin M, Skouw-Rasmussen N, et al. European principles of care for women and girls with inherited bleeding disorders. Haemoph Off J World Fed Hemoph. 2021;27(5):837–847.
  • Kalot MA, Al-Khatib M, Connell NT, et al. An international survey to inform priorities for new guidelines on von Willebrand disease. Haemoph Off J World Fed Hemoph. 2020;26(1):106–116.
  • Mauser-Bunschoten EP, Kadir RA, Laan ETM, et al. Managing women-specific bleeding in inherited bleeding disorders: a multidisciplinary approach. Haemoph Off J World Fed Hemoph. 2021;27(3):463–469.
  • Connell NT, James PD, Brignardello-Petersen R, et al. von Willebrand disease: proposing definitions for future research. Blood Adv. 2021;5(2):565–569.
  • Denis CV, Susen S, Lenting PJ. von Willebrand disease: what does the future hold? Blood. 2021;137(17):2299–2306.
  • Lenting PJ, Kizlik-Manson C, Casari C. Towards novel treatment options in von Willebrand disease. Haemoph Off J World Fed Hemoph. 2022;28(Suppl 4):5–10.
  • Doshi BS, Rogers RS, Whitworth HB, et al. Utility of repeat testing in the evaluation for von Willebrand disease in pediatric patients. J Thromb Haemost JTH. 2019;17(11):1838–1847.
  • Weyand AC, Kouides P, Malvar J, et al. Is ≥ 100% the magic number to rule out the laboratory diagnosis of von W illebrand disease based on initial testing? Am J Hematol. 2021;96(11):E439–E441.
  • Bayer LL, Hillard PJA. Use of levonorgestrel intrauterine system for medical indications in adolescents. J Adolesc Health Off Publ Soc Adolesc Med. 2013;52(4):S54–58.
  • International Perspectives: AD. IUDs and Adolescents. J Pediatr Adolesc Gynecol. 2019;32(5):S36–S42.
  • Lim MY, Olson L, Rajpurkar MA, et al. Concomitant use of combined hormonal contraceptives and antifibrinolytic agents for the management of heavy menstrual bleeding: a practice pattern survey. Thromb Res. 2021;204:95–100.
  • Kouides P, Wawra-Hehenberger K, Sajan A, et al. Safety of a pasteurized plasma-derived factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data. Transfusion (Paris). 2017;57(10):2390–2403.
  • Peyvandi F, Kouides P, Turecek PL, et al. Evolution of replacement therapy for von Willebrand disease: from plasma fraction to recombinant von Willebrand factor. Blood Rev. 2019;38:100572.
  • Krayenbuehl P-A, Battegay E, Breymann C, et al. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood. 2011;118(12):3222–3227.
  • Stoffel NU, Zeder C, Brittenham GM, et al. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020;105(5):1232–1239.
  • Mannucci PM. How I treat patients with von Willebrand disease. Blood. 2001;97(7):1915–1919.
  • Reale SC, Easter SR, Xu X, et al. Trends in postpartum hemorrhage in the United States From 2010 to 2014. Anesth Analg. 2020;130(5):e119–e122.
  • Kazi S, Arusi I, McLeod A, et al. Postpartum hemorrhage in women with von Willebrand disease: consider other etiologies. J Obstet Gynaecol Can. 2022;44(9):972–977.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.