Enhanced peripartum hemostatic management does not decrease postpartum hemorrhage incidence in hemophilia carriers: the Pregnancy and Inherited Bleeding Disorders study

Journal of Thrombosis and Haemostasis, vol. 24, pp. 2061–2070

Abstract

BACKGROUND: Pregnant hemophilia carriers receive prophylactic factor [F]VIII or FIX concentrate based on third trimester FVIII/FIX activity to reduce the risk of severe postpartum hemorrhage (PPH, ≥ 1000 mL). Due to persistently high severe PPH rates, Dutch guidelines were revised in 2018. Consensus was reached to increase the third trimester threshold for prophylaxis from < 50 to < 80 IU/dL and peak target levels during childbirth from ≥ 100 to ≥ 150 IU/dL. OBJECTIVES: To assess the severe PPH incidence after guideline revision. METHODS: Pregnant hemophilia carriers were prospectively enrolled (2018-2024) in Dutch hemophilia treatment centers to assess the severe PPH incidence after implementation of the revised guideline. FVIII/FIX activity and hematologic and obstetric outcomes were recorded and compared with a historical cohort (2012-2017). Statistics included descriptives and logistic regression to correct for confounders. RESULTS: Severe PPH occurred in 12.4% of 170 deliveries. No thrombosis was recorded. Prophylaxis in the subgroup with third trimester levels of < 80 IU/dL led to similar PPH rates to those with spontaneous rises of > 80 IU/dL. Compared with the historic cohort with the third trimester cutoff of < 50 IU/dL, the severe PPH incidence did not decrease (n = 170 vs n = 197; odds ratio, 1.16; 95% CI, 0.46-2.93), neither in the third trimester of the 50- to 80-IU/dL subgroup (n = 28/170 vs n = 21/197; odds ratio, 1.0; 95% CI, 0.20-2.90). CONCLUSION: Increasing the third trimester cutoff to < 80 IU/dL and aiming for ≥ 150 IU/dL at delivery did not decrease the risk for severe PPH in hemophilia carriers. More research is needed on optimal clotting factor levels during delivery to prevent severe PPH.

Authors 16

1. Anne de Vaan corresponding

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Division of Internal Medicine and Dermatology, Center for Benign Haematology, Thrombosis and Haemostasis, van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: a.devaan-2@umcutrecht.nl

2. MJHA Kruip

   Erasmus MC · Erasmus University Rotterdam

   Affiliation as printed

   Department of Hematology, Department of Quality and Patient Care, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands

3. Jeroen C.J. Eikenboom Aachen Department of Internal Medicine Division of Thrombosis and Hemostasis

   Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands

4. Marieke C. Punt

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Division of Internal Medicine and Dermatology, Center for Benign Haematology, Thrombosis and Haemostasis, van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

5. Michiel Coppens

   Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam

   Affiliation as printed

   Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands

6. Laurens Nieuwenhuizen

   Máxima Medisch Centrum

   Affiliation as printed

   Department of Haematology, Maxima Medisch Centrum, Eindhoven, the Netherlands

7. Saskia E.M. Schols

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Hematology, Radboud University Medical Center and Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, the Netherlands

8. Anja Mäkelburg

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

9. Floor C. J. I. Heubel-Moenen

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Hematology-Internal Medicine, Maastricht University Medical Center+ and Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht and CARIM, Maastricht University, Maastricht, the Netherlands

10. J.J. Duvekot

    Erasmus MC

    Affiliation as printed

    Department of Obstetrics, Erasmus MC, Erasmus University Medical Center, Rotterdam, the Netherlands

11. Marjolein Peters

    Emma Kinderziekenhuis · Amsterdam University Medical Centers

    Affiliation as printed

    Department of Pediatric Hematology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands

12. Annemieke Middeldorp Aachen Department of Obstetrics, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Obstetrics, Leiden University Medical Center, Leiden, the Netherlands

13. Kitty W.M. Bloemenkamp

    University Medical Center Utrecht · Wilhelmina Children's Hospital

    Affiliation as printed

    Department of Woman and Baby, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands

14. Roger E. G. Schutgens

    Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Division of Internal Medicine and Dermatology, Center for Benign Haematology, Thrombosis and Haemostasis, van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

15. dr. A.T. Lely

    University Medical Center Utrecht · Wilhelmina Children's Hospital

    Affiliation as printed

    Department of Woman and Baby, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands

16. Karin P. M. van Galen

    Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Division of Internal Medicine and Dermatology, Center for Benign Haematology, Thrombosis and Haemostasis, van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: k.p.m.vangalen@umcutrecht.nl