Postpartum Hemorrhage in Women with Von Willebrand Disease - A Retrospective Observational Study

Igor Govorov, Signe Löfgren, Roza Chaireti, Margareta Holmström, Katarina Bremme, Miriam Mints, Igor Govorov, Signe Löfgren, Roza Chaireti, Margareta Holmström, Katarina Bremme, Miriam Mints

Abstract

Introduction: von Willebrand disease (VWD) is a hereditary bleeding disorder, caused by a deficiency in the levels and/or function of von Willebrand factor (VWF). Women with VWD appear to be at increased risk of experiencing postpartum hemorrhage (PPH), though the levels of VWF increase during pregnancy. There is limited knowledge of how PPH is associated with the subtype of VWD, plasma levels of other coagulations factors than VWF and given hemostatic treatment.

Aims: The aims were to investigate the incidence of PPH in women with VWD and to analyse the correlation between PPH and: (1) type of VWD, (2) laboratory monitoring of VWF and FVIII and (3) hemostatic drug treatment.

Methods: This was a retrospective observational study. The study participants (n = 34) were recruited from the Coagulation Unit, Karolinska University hospital. Fifty-nine deliveries, which occurred in 14 different obstetrics units (years 1995-2012) were included in the study.

Results: The incidence of primary PPH was 44%, severe primary PPH 20% and secondary PPH 12%. VWD type 3 was associated with a higher risk of experiencing severe primary PPH compared to other subtypes. FVIII:C in pregnancy was inversely correlated to blood loss during delivery. There was a significantly higher incidence of secondary PPH when the VWD diagnosis was unknown at time of delivery.

Conclusions: The women with VWD are at higher risk of PPH, especially those with type 3 VWD or when diagnosis is unknown prior to delivery. Identification of pregnant women with undiagnosed VWD may be of importance in order to prevent PPH.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flowchart for inclusion process.
Fig 1. Flowchart for inclusion process.
Fig 2. Distribution of blood loss.
Fig 2. Distribution of blood loss.
Fig 3. Blood loss (ml) in association…
Fig 3. Blood loss (ml) in association with delivery in the different subtypes of von Willebrand disease (VWD).
Fig 4. Total dose of clotting factor…
Fig 4. Total dose of clotting factor concentrate (CFC) in the three different subtypes of von Willebrand disease (VWD).

References

    1. von Willebrand E. Hereditary pseudohaemophilia (historical annotation). Haemophilia. 1999;(5):223–31.
    1. Lak M, Peyvandi F, Mannucci PM. Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von Willebrand disease. Br J Haematol. 2000;111(4):1236–9. .
    1. Schneppenheim R. The pathophysiology of von Willebrand disease: therapeutic implications. Thromb Res. 2011;128:S3–S7. 10.1016/S0049-3848(12)70002-6
    1. Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: a 2004 update. Semin Hematol. 2005;42(1):15–28. .
    1. Biron C, Mahieu B, Rochette A, Capdevila X, Castex A, Amiral J, et al. Preoperative screening for von Willebrand disease type 1: low yield and limited ability to predict bleeding. The Journal of laboratory and clinical medicine. 1999;134(6):605–9. Epub 1999/12/14. .
    1. Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood. 1987;69(2):454–9. .
    1. Sadler JE, Mannucci PM, Berntorp E, Bochkov N, Boulyjenkov V, Ginsburg D, et al. Impact, diagnosis and treatment of von Willebrand disease. Thrombosis and haemostasis. 2000;84(2):160–74. Epub 2000/08/26. .
    1. Berntorp E. Prevalence of von Willebrand disease in the Nordic Region. Haematologica reports. 2005;1(4):4–6.
    1. James AH. Von Willebrand disease in women: awareness and diagnosis. Thromb Res. 2009;124 Suppl 1:S7–10. 10.1016/S0049-3848(09)70151-3 .
    1. Oyelese Y, Ananth CV. Postpartum hemorrhage: epidemiology, risk factors, and causes. Clinical obstetrics and gynecology. 2010;53(1):147–56. Epub 2010/02/10. 10.1097/GRF.0b013e3181cc406d .
    1. Rath WH. Postpartum hemorrhage—update on problems of definitions and diagnosis. Acta obstetricia et gynecologica Scandinavica. 2011;90(5):421–8. Epub 2011/02/22. 10.1111/j.1600-0412.2011.01107.x .
    1. Mehrabadi A, Hutcheon JA, Lee L, Liston RM, Joseph KS. Trends in postpartum hemorrhage from 2000 to 2009: a population-based study. BMC pregnancy and childbirth. 2012;12:108 Epub 2012/10/13. 10.1186/1471-2393-12-108
    1. Bais JM, Eskes M, Pel M, Bonsel GJ, Bleker OP. Postpartum haemorrhage in nulliparous women: incidence and risk factors in low and high risk women. A Dutch population-based cohort study on standard (> or = 500 ml) and severe (> or = 1000 ml) postpartum haemorrhage. European journal of obstetrics, gynecology, and reproductive biology. 2004;115(2):166–72. Epub 2004/07/21. 10.1016/j.ejogrb.2003.12.008 .
    1. Knight M, Callaghan WM, Berg C, Alexander S, Bouvier-Colle MH, Ford JB, et al. Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group. BMC pregnancy and childbirth. 2009;9:55 Epub 2009/12/01. 10.1186/1471-2393-9-55
    1. Mousa HA, Alfirevic Z. Treatment for primary postpartum haemorrhage. Cochrane Database Syst Rev. 2007;(1):CD003249 Epub 2007/01/27. 10.1002/14651858.CD003249.pub2 .
    1. Jangsten E, Mattsson LA, Lyckestam I, Hellstrom AL, Berg M. A comparison of active management and expectant management of the third stage of labour: a Swedish randomised controlled trial. BJOG: an international journal of obstetrics and gynaecology. 2011;118(3):362–9. Epub 2010/12/08. 10.1111/j.1471-0528.2010.02800.x .
    1. Combs CA, Murphy EL, Laros RK Jr. Factors associated with postpartum hemorrhage with vaginal birth. Obstetrics and gynecology. 1991;77(1):69–76. Epub 1991/01/11. .
    1. Siboni SM, Spreafico M, Calo L, Maino A, Santagostino E, Federici AB, et al. Gynaecological and obstetrical problems in women with different bleeding disorders. Haemophilia. 2009;15(6):1291–9. 10.1111/j.1365-2516.2009.02072.x .
    1. 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):1165–9. Epub 2007/04/04. 10.1111/j.1538-7836.2007.02563.x .
    1. Kirtava A, Crudder S, Dilley A, Lally C, Evatt B. Trends in clinical management of women with von Willebrand disease: a survey of 75 women enrolled in haemophilia treatment centres in the United States. Haemophilia. 2004;10(2):158–61. .
    1. Foster PA. The reproductive health of women with von Willebrand Disease unresponsive to DDAVP: results of an international survey. On behalf of the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the ISTH. Thromb Haemost. 1995;74(2):784–90. Epub 1995/08/01. .
    1. Kirtava A, Drews C, Lally C, Dilley A, Evatt B. Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand's disease receiving care in haemophilia treatment centres: a case-control study. Haemophilia. 2003;9(3):292–7. .
    1. Kouides PA, Phatak PD, Burkart P, Braggins C, Cox C, Bernstein Z, et al. Gynaecological and obstetrical morbidity in women with type I von Willebrand disease: results of a patient survey. Haemophilia. 2000;6(6):643–8. .
    1. Ramsahoye BH, Davies SV, Dasani H, Pearson JF. Pregnancy in von Willebrand's disease. J Clin Pathol. 1994;47(6):569–70.
    1. Abdul-Kadir R, McLintock C, Ducloy AS, El-Refaey H, England A, Federici AB, et al. Evaluation and management of postpartum hemorrhage: consensus from an international expert panel. Transfusion (Paris). 2014;54(7):1756–68. 10.1111/trf.12550. WOS:000340600100011.
    1. Mannucci PM. Treatment of von Willebrand's Disease. N Engl J Med. 2004;351(7):683–94. Epub 2004/08/13. 10.1056/NEJMra040403 .
    1. Scott JP, Montgomery RR, Retzinger GS. Dimeric ristocetin flocculates proteins, binds to platelets, and mediates von Willebrand factor-dependent agglutination of platelets. The Journal of biological chemistry. 1991;266(13):8149–55. Epub 1991/05/05. .
    1. Macfarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, McPherson J. Letter: A method for assaying von Willebrand factor (ristocetin cofactor). Thrombosis et diathesis haemorrhagica. 1975;34(1):306–8. Epub 1975/09/30. .
    1. Veyradier A, Fressinaud E, Meyer D. Laboratory diagnosis of von Willebrand disease. International journal of clinical & laboratory research. 1998;28(4):201–10. Epub 1999/01/08. .
    1. Rosen S. Assay of factor VIII:C with a chromogenic substrate. Scandinavian journal of haematology Supplementum. 1984;40:139–45. Epub 1984/01/01. .
    1. Shakur H, Elbourne D, Gulmezoglu M, Alfirevic Z, Ronsmans C, Allen E, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials. 2010;11:40 10.1186/1745-6215-11-40
    1. Pacheco LD, Costantine MM, Saade GR, Mucowski S, Hankins GD, Sciscione AC. von Willebrand disease and pregnancy: a practical approach for the diagnosis and treatment. Am J Obstet Gynecol. 2010;203(3):194–200. Epub 2010/04/27. 10.1016/j.ajog.2010.02.036 .
    1. James AH, Kouides PA, Abdul-Kadir R, Edlund M, Federici AB, Halimeh S, 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):8 10.1016/j.ajog.2009.04.024. WOS:000267599300005.
    1. 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. 10.1016/j.ajog.2010.02.036. WOS:000281602700004.
    1. Bolte A, Bouma L, Van Geijn H, editors. Medical therapies for primary postpartum hemorrhage. International Congress Series; 2005: Elsevier.
    1. Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999;57(6):1005–32. Epub 1999/07/10. .
    1. Holmgren PA. Postpartumblödningar In: Hagberg H, Marsal K., Westgren M., editor. Obstetrik. Lund: Studentlitteratur; 2008.
    1. 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):314–21. .
    1. Stoof SCM, van Steenbergen HW, Zwagemaker A, Sanders YV, Cannegieter SC, Duvekot JJ, et al. Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: a retrospective survey. Haemophilia. 2015;21(4):505–12. 10.1111/hae.12635. WOS:000356875600032.
    1. Larsson C, Saltvedt S, Wiklund I, Pahlen S, Andolf E. Estimation of blood loss after cesarean section and vaginal delivery has low validity with a tendency to exaggeration. Acta obstetricia et gynecologica Scandinavica. 2006;85(12):1448–52. Epub 2007/01/30. 10.1080/00016340600985032 .
    1. Huq FY, Kadir RA. Management of pregnancy, labour and delivery in women with inherited bleeding disorders. Haemophilia. 2011;17:20–30. 10.1111/j.1365-2516.2011.02561.x. WOS:000292103700006.
    1. Chee YL, Townend J, Crowther M, Smith N, Watson HG. Assessment of von Willebrand disease as a risk factor for primary postpartum haemorrhage. Haemophilia. 2012;18(4):593–7. Epub 2012/02/18. 10.1111/j.1365-2516.2012.02750.x .
    1. Lassila R, Holme PA, Landorph A, Petrini P, Onundarson PT, Hillarp A. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease. Semin Thromb Hemost. 2011;37(5):495–502. 10.1055/s-0031-1281034 .
    1. James AH. Diagnosis and management of women with bleeding disorders—international guidelines and consensus from an international expert panel. Haemophilia: the official journal of the World Federation of Hemophilia. 2011;17 Suppl 1:3–5. Epub 2011/07/01. 10.1111/j.1365-2516.2011.02557.x .
    1. Chi C, Kadir RA. Inherited bleeding disorders in pregnancy. Best practice & research Clinical obstetrics & gynaecology. 2012;26(1):103–17. Epub 2011/11/22. 10.1016/j.bpobgyn.2011.10.005 .
    1. 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):140–4. 10.1111/j.1365-2516.1995.tb00056.x
    1. 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):282–5. .
    1. Chediak JR, Alban GM, Maxey B. von Willebrand's disease and pregnancy: management during delivery and outcome of offspring. Am J Obstet Gynecol. 1986;155(3):618–24.

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