Download PDF
Thromb Haemost 2016; 116(S 01): S18-S25
DOI: 10.1160/TH16-01-0050
5th International Coagulation Meeting 2015 – Barcelona, Spain
Schattauer GmbH

Contemporary issues in the management of von Willebrand disease

Augusto B. Federici
1   Hematology and Transfusion Medicine, L. Sacco University Hospital, Milan, Italy
2   Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy
,
Christoph Königs
3   Department of Paediatrics, Clinical and Molecular Haemostasis, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
,
Andra H. James
4   Department of Obstetrics & Gynecology, Duke University, Durham, North Carolina, USA
› Author Affiliations
Further Information

Publication History

Received: 20 January 2016

Accepted after major revision: 22 June 2016

Publication Date:
15 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Bleeding scores in VWD, focused in particular on mucosal bleeding, can be very useful in the diagnosis and validation of different types of treatment. The results of an extended prospective study with a large amount of information on clinical phenotype and implications in treatment are reviewed in this article. Treatment of mucosal and joint bleeding in severe VWD remains difficult in some patients. Due to the lack of data on the use of prophylaxis in these patients it is difficult to establish optimal treatment regimens. An overview of the literature, with a focus on the ongoing PRO.WILL study, is provided here. Furthermore, understanding the changes in von Willebrand factor (VWF) levels during pregnancy is very important for establishing the optimal management strategy for pregnancy and delivery in women with VWD. A recently published prospective observational cohort study in women with and without VWD during the postpartum period provides important data that should allow the improvement of postpartum treatment protocols.

Keywords

von Willebrand disease - prophylaxis - pregnancy - bleeding score - FVIII/VWF concentrates
 

  • References

  • 1 Federici AB, Bucciarelli P, Castaman G. et al. Management of inherited von Willebrand disease in Italy: results from the retrospective study on 1234 patients. Semin Thromb Hemost 2011; 37: 511-521.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Federici AB, Bucciarelli P, Castaman G. et al. The bleeding score predicts clinical outcomes and replacement therapy in adults with von Willebrand disease. Blood 2014; 123: 4037-4044.
    CrossrefPubMedGoogle Scholar
  • 3 Tosetto A, Rodeghiero F, Castaman G. et al. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). J Thromb Haemost 2006; 04: 766-773.
    CrossrefPubMedGoogle Scholar
  • 4 Type 3 von Willebrand International Registries Inhibitor Prospective Study (3WINTERS-IPS). Available from www.vwd-3winters-ips.com Accessed November 4, 2015.
    PubMedGoogle Scholar
  • 5 Federici AB, Mannucci PM, Castaman G. et al. Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients. Blood 2009; 113: 526-534.
    CrossrefPubMedGoogle Scholar
  • 6 Castaman G, Tosetto A, Federici AB. et al. Bleeding tendency and efficacy of anti-haemorrhagic treatments in patients with type 1 von Willebrand disease and increased von Willebrand factor clearance. Thromb Haemost 2011; 105: 647-654.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Castaman G, Federici AB, Tosetto A. et al. Different bleeding risk in type 2A and 2M von Willebrand disease: a 2-year prospective study in 107 patients. J Thromb Haemost 2012; 10: 632-638.
    CrossrefPubMedGoogle Scholar
  • 8 Nilsson IM, Berntorp E, Löfqvist T. et al. Twenty-five years’ experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 1992; 232: 25-32.
    CrossrefPubMedGoogle Scholar
  • 9 Ljung R, Gretenkort NAndersson. The current status of prophylactic replacement therapy in children and adults with haemophilia. Br J Haematol 2015; 169: 777-786.
    CrossrefPubMedGoogle Scholar
  • 10 Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood 2015; 125: 2038-2044.
    CrossrefPubMedGoogle Scholar
  • 11 Mannucci PM, Ruggeri ZM, Pareti FI. et al. 1-Deamino-8-d-arginine vasopress-in: a new pharmacological approach to the management of haemophilia and von Willebrands’ diseases. Lancet 1977; 01: 869-872.
    PubMedGoogle Scholar
  • 12 Castaman G, Goodeve A, Eikenboom J. et al. Principles of care for the diagnosis and treatment of von Willebrand disease. Haematologica 2013; 98: 667-674.
    CrossrefPubMedGoogle Scholar
  • 13 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: 453-465.
    CrossrefPubMedGoogle Scholar
  • 14 Berntorp E, Abshire T. vWD PN Steering Committee. The von Willebrand disease prophylaxis network (vWD PN): exploring a treatment concept. Thromb Res 2006; 118 (Suppl. 01) S19-S22.
    CrossrefPubMedGoogle Scholar
  • 15 Berntorp E, Petrini P. Long-term prophylaxis in von Willebrand disease. Blood Coagul Fibrinolysis 2005; 16 (Suppl. 01) S23-S26.
    CrossrefPubMedGoogle Scholar
  • 16 Berntorp E. Prophylaxis in von Willebrand disease. Haemophilia 2008; 14 (Suppl. 05) 47-53.
    CrossrefPubMedGoogle Scholar
  • 17 Halimeh S, Krümpel A, Rott H. et al. Long-term secondary prophylaxis in children, adolescents and young adults with von Willebrand disease. Results of a cohort study. Thromb Haemost 2011; 105: 597-604.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Abshire TC, Federici AB, Alvárez MT. et al. Prophylaxis in severe forms of von Willebrand’s disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN). Haemophilia 2013; 19: 76-81.
    CrossrefPubMedGoogle Scholar
  • 19 Abshire T, Cox-Gill J, Kempton CL. et al. Prophylaxis escalation in severe von Willebrand disease: a prospective study from the von Willebrand Disease Prophylaxis Network. J Thromb Haemost 2015; 13: 1585-1589.
    CrossrefPubMedGoogle Scholar
  • 20 Holm E, Abshire TC, Bowen J. et al. Changes in bleeding patterns in von Wille-brand disease after institution of long-term replacement therapy: results from the von Willebrand Disease Prophylaxis Network. Blood Coagul Fibrinolysis 2015; 26: 383-388.
    CrossrefPubMedGoogle Scholar
  • 21 Kavakli K, Yang R, Rusen L. et al. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II). J Thromb Haemost 2015; 13: 360-369.
    CrossrefPubMedGoogle Scholar
  • 22 Federici AB. Highly purified VWF/FVIII concentrates in the treatment and prophylaxis of von Willebrand disease: the PRO. WILL Study. Haemophilia 2007; 13 (Suppl. 05) 15-24.
    CrossrefPubMedGoogle Scholar
  • 23 Peyvandi F, Federici AB. Secondary prophylaxis in von Willebrand disease with highly purified VWF/FVIII concentrates: interim results of the PRO.WILL study [abstract VWF25]. J Thromb Haemost 2014; 12 (Suppl. 01) 98.
    PubMedGoogle Scholar
  • 24 Kouides PA. Obstetric and gynaecological aspects of von Willebrand disease. Best Pract Res Clin Haematol 2001; 14: 381-399.
    CrossrefPubMedGoogle Scholar
  • 25 Kujovich JL. von Willebrand disease and pregnancy. J Thromb Haemost 2005; 03: 246-253.
    CrossrefPubMedGoogle Scholar
  • 26 James AH, Jamison MG. Bleeding events and other complications during pregnancy and childbirth in women with von Willebrand disease. J Thromb Haemost 2007; 05: 1165-1169.
    CrossrefPubMedGoogle Scholar
  • 27 Al-Zirqi I, Vangen S, Forsen L. et al. Prevalence and risk factors of severe obstetric haemorrhage. Br J Obstet Gynecol 2008; 115: 1265-1272.
    CrossrefPubMedGoogle Scholar
  • 28 Shahbazi S, Moghaddam-Banaem L, Ekhtesari F. et al. Impact of inherited bleeding disorders on pregnancy and postpartum hemorrhage. Blood Coagul Fibrinolysis 2012; 23: 603-607.
    CrossrefPubMedGoogle Scholar
  • 29 US National Institute of Health/National Heart, Lung, and Blood Institute. Management of von Willebrand disease. Available from: www.nhlbi.nih.gov/health-pro/guidelines/current/von-willebrand-guidelines/full-report/4-management-of-vwd Accessed November 10, 2015.
    PubMedGoogle Scholar
  • 30 Sanchez-Luceros A, Meschengieser SS, Marchese C. et al. Factor VIII and von Willebrand factor changes during normal pregnancy and puerperium. Blood Coagul Fibrinolysis 2003; 14: 647-651.
    CrossrefPubMedGoogle Scholar
  • 31 Wickstrom K, Edelstam G, Lowbeer CH. et al. 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: 31-40.
    CrossrefPubMedGoogle Scholar
  • 32 Huq FY, Kulkarni A, Agbim EC. et al. Changes in the levels of factor VIII and von Willebrand factor in the puerperium. Haemophilia 2012; 18: 241-245.
    CrossrefPubMedGoogle Scholar
  • 33 Caliezi C, Tsakiris DA, Behringer H. et al. Two consecutive pregnancies and deliveries in a patient with von Willebrand’s disease type 3. Haemophilia 1998; 04: 845-849.
    CrossrefPubMedGoogle Scholar
  • 34 U. S. Department of Health and Human Services. National Institutes of Health, National Heart, Lung and Blood Institute. The diagnosis, evaluation, and management of von Willebrand disease. Available from: www.nhlbi.nih.gov/files/docs/guidelines/vwd.pdf Accessed November 12, 2015.
    PubMedGoogle Scholar
  • 35 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. Haemophilia 2015; 21: 81-87.
    CrossrefPubMedGoogle Scholar