Download PDF
Semin Thromb Hemost 2016; 42(07): 717-723
DOI: 10.1055/s-0036-1587686
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Von Willebrand Disease and Pregnancy: A Review of Evidence and Expert Opinion

Emily Reynen
1   Department of Medicine, Queen's University, Kingston, Ontario, Canada
,
Paula James
1   Department of Medicine, Queen's University, Kingston, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Publication Date:
20 September 2016 (online)

    Permissions and Reprints

Abstract

von Willebrand disease (VWD) is a common, inherited bleeding disorder. There are three main types of VWD, which result in a quantitative or qualitative deficiency in von Willebrand factor (VWF) and in severe cases, also Factor VIII (FVIII). The severity of bleeding depends on the underlying pathophysiology. Type 1 VWD is usually mild, while types 2 or 3 VWD can be associated with moderate or significant bleeding. Managing pregnant women with VWD requires a multidisciplinary approach. Such patients are at increased risk of postpartum hemorrhage. Whether women with VWD are at increased risk of spontaneous abortion remains unclear. Because of increased risk of bleeding, there are special considerations for delivery and obstetrical analgesia. There is a lack of high-quality evidence supporting monitoring and treatment of VWD in pregnancy. Most experts recommend that FVIII and VWF levels be monitored prior to delivery and treatment initiated when levels remain below 0.50 IU/mL. Some experts consider desmopressin (DDAVP) to be the preferred initial treatment in type 1 and most type 2 VWD. DDAVP is relatively contraindicated in type 2B disease. Plasma-derived FVIII and VWF replacements are the treatment of choice in type 2B and 3 VWD and in type 1 or 2 VWD when patients do not respond to DDAVP.

Keywords

pregnancy - von Willebrand disease - coagulopathy - hemostasis - hemorrhage
 

  • References

  • 1 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
    CrossrefPubMedGoogle Scholar
  • 2 Inocêncio G, Braga A, Azevedo S, Buchner G. Management of von Willebrand disease type 3 during pregnancy - 2 cases reports. Eur Rev Med Pharmacol Sci 2013; 17 (21) 2857-2859
    PubMedGoogle Scholar
  • 3 Lipe BC, Dumas MA, Ornstein DL. Von Willebrand disease in pregnancy. Hematol Oncol Clin North Am 2011; 25 (2) 335-358 , viii
    CrossrefPubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 Woods AI, Sánchez-Luceros A, Meschengieser SS, Kempfer AC, Blanco AN, Lazzari MA. Diagnosis and management of von Willebrand disease in a single institution of Argentina. Semin Thromb Hemost 2011; 37 (5) 568-575
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Kujovich JL. von Willebrand disease and pregnancy. J Thromb Haemost 2005; 3 (2) 246-253
    CrossrefPubMedGoogle Scholar
  • 7 Mannucci PM. Treatment of von Willebrand's disease. N Engl J Med 2004; 351 (7) 683-694
    CrossrefPubMedGoogle Scholar
  • 8 Lee CA, Chi C, Pavord SR , et al; UK Haemophilia Centre Doctors' Organization. The obstetric and gynaecological management of women with inherited bleeding disorders—review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors' Organization. Haemophilia 2006; 12 (4) 301-336
    CrossrefPubMedGoogle Scholar
  • 9 Ranger A, Manning RA, Lyall H, Laffan MA, Millar CM. Pregnancy in type 2B VWD: a case series. Haemophilia 2012; 18 (3) 406-412
    CrossrefPubMedGoogle Scholar
  • 10 Rodeghiero F. von Willebrand disease: still an intriguing disorder in the era of molecular medicine. Haemophilia 2002; 8 (3) 292-300
    CrossrefPubMedGoogle Scholar
  • 11 James AH, Jamison MG. Bleeding events and other complications during pregnancy and childbirth in women with von Willebrand disease. J Thromb Haemost 2007; 5 (6) 1165-1169
    CrossrefPubMedGoogle Scholar
  • 12 Dilley A, Drews C, Lally C, Austin H, Barnhart E, Evatt B. A survey of gynecologists concerning menorrhagia: perceptions of bleeding disorders as a possible cause. J Womens Health Gend Based Med 2002; 11 (1) 39-44
    CrossrefPubMedGoogle Scholar
  • 13 Wickström K, Edelstam G, Löwbeer CH, Hansson LO, Siegbahn A. Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy. Scand J Clin Lab Invest 2004; 64 (1) 31-40
    CrossrefPubMedGoogle Scholar
  • 14 Peyvandi F, Bidlingmaier C, Garagiola I. Management of pregnancy and delivery in women with inherited bleeding disorders. Semin Fetal Neonatal Med 2011; 16 (6) 311-317
    CrossrefPubMedGoogle Scholar
  • 15 Shahbazi S, Moghaddam-Banaem L, Ekhtesari F, Ala FA. Impact of inherited bleeding disorders on pregnancy and postpartum hemorrhage. Blood Coagul Fibrinolysis 2012; 23 (7) 603-607
    CrossrefPubMedGoogle Scholar
  • 16 James AH, Kouides PA, Abdul-Kadir R , et al. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel. Am J Obstet Gynecol 2009; 201 (1) 12.e1-12.e8
    CrossrefPubMedGoogle Scholar
  • 17 Conti M, Mari D, Conti E, Muggiasca ML, Mannucci PM. Pregnancy in women with different types of von Willebrand disease. Obstet Gynecol 1986; 68 (2) 282-285
    PubMedGoogle Scholar
  • 18 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). Haemophilia 2008; 14 (2) 171-232
    CrossrefPubMedGoogle Scholar
  • 19 Rick ME, Williams SB, Sacher RA, McKeown LP. Thrombocytopenia associated with pregnancy in a patient with type IIB von Willebrand's disease. Blood 1987; 69 (3) 786-789
    CrossrefPubMedGoogle Scholar
  • 20 Kadir RA, Lee CA, Sabin CA, Pollard D, Economides DL. Pregnancy in women with von Willebrand's disease or factor XI deficiency. Br J Obstet Gynaecol 1998; 105 (3) 314-321
    CrossrefPubMedGoogle Scholar
  • 21 Rydz N, James PD. The evolution and value of bleeding assessment tools. J Thromb Haemost 2012; 10 (11) 2223-2229
    CrossrefPubMedGoogle Scholar
  • 22 Pacheco LD, Costantine MM, Saade GR, Mucowski S, Hankins GDV, Sciscione AC. von Willebrand disease and pregnancy: a practical approach for the diagnosis and treatment. Am J Obstet Gynecol 2010; 203 (3) 194-200
    CrossrefPubMedGoogle Scholar
  • 23 Favaloro EJ, Thom J, Baker R ; Australasian Society for Thrombosis and Haemostasis (ASTH) Emerging Technologies Group. Assessment of current diagnostic practice and efficacy in testing for von Willebrand's disorder: results from the second Australasian multi-laboratory survey. Blood Coagul Fibrinolysis 2000; 11 (8) 729-737
    CrossrefPubMedGoogle Scholar
  • 24 Favaloro EJ. Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays. Blood Coagul Fibrinolysis 2011; 22 (7) 553-564
    CrossrefPubMedGoogle Scholar
  • 25 Laffan MA, Lester W, O'Donnell JS , et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol 2014; 167 (4) 453-465
    CrossrefPubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Ito M, Yoshimura K, Toyoda N, Wada H. Pregnancy and delivery in patients with von Willebrand's disease. J Obstet Gynaecol Res 1997; 23 (1) 37-43
    CrossrefPubMedGoogle Scholar
  • 28 Komada T, Kawasaki T, Sata T. [Anesthetic management of emergency cesarean section in a patient with acquired von Willebrand syndrome]. Masui 2013; 62 (11) 1368-1371
    PubMedGoogle Scholar
  • 29 Kouides PA. Obstetric and gynaecological aspects of von Willebrand disease. Best Pract Res Clin Haematol 2001; 14 (2) 381-399
    CrossrefPubMedGoogle Scholar
  • 30 Amorde RW, Patel SN, Pagel PS. Management of labor and delivery of a patient with Von Willebrand disease type 2A. Int Anesthesiol Clin 2011; 49 (2) 74-80
    CrossrefPubMedGoogle Scholar
  • 31 Castaman G, Tosetto A, Rodeghiero F. Pregnancy and delivery in women with von Willebrand's disease and different von Willebrand factor mutations. Haematologica 2010; 95 (6) 963-969
    CrossrefPubMedGoogle Scholar
  • 32 Ramsahoye BH, Davies SV, Dasani H, Pearson JF. Obstetric management in von Willebrand's disease: a report of 24 pregnancies and a reivesw of the literature. Haemophilia 1995; 1 (2) 140-144
    CrossrefPubMedGoogle Scholar
  • 33 Greer IA, Lowe GD, Walker JJ, Forbes CD. Haemorrhagic problems in obstetrics and gynaecology in patients with congenital coagulopathies. Br J Obstet Gynaecol 1991; 98 (9) 909-918
    CrossrefPubMedGoogle Scholar
  • 34 Huq FY, Kulkarni A, Agbim EC, Riddell A, Tuddenham E, Kadir RA. Changes in the levels of factor VIII and von Willebrand factor in the puerperium. Haemophilia 2012; 18 (2) 241-245
    CrossrefPubMedGoogle Scholar
  • 35 Mannucci PM. How I treat patients with von Willebrand disease. Blood 2001; 97 (7) 1915-1919
    CrossrefPubMedGoogle Scholar
  • 36 Sánchez-Luceros A, Meschengieser SS, Turdó K , et al. Evaluation of the clinical safety of desmopressin during pregnancy in women with a low plasmatic von Willebrand factor level and bleeding history. Thromb Res 2007; 120 (3) 387-390
    CrossrefPubMedGoogle Scholar
  • 37 Casonato A, Pontara E, Sartorello F , et al. Reduced von Willebrand factor survival in type Vicenza von Willebrand disease. Blood 2002; 99 (1) 180-184
    CrossrefPubMedGoogle Scholar
  • 38 Haberichter SL, Balistreri M, Christopherson P , et al. Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival. Blood 2006; 108 (10) 3344-3351
    CrossrefPubMedGoogle Scholar
  • 39 Haberichter SL. von Willebrand factor propeptide: biology and clinical utility. Blood 2015; 126 (15) 1753-1761
    CrossrefPubMedGoogle Scholar