Higher-Dosed Clotting Factor Prophylaxis Fails to Reduce Postpartum Hemorrhage in Women With von Willebrand Disease: findings from the observational PRegnancy and Inherited bleeding DisordErS study

Abstract

Background Pregnant women with von Willebrand disease (VWD) receive prophylactic von Willebrand factor (VWF) concentrate based on third trimester VWF/factor (F)VIII levels to reduce the risk of severe postpartum hemorrhage (PPH, ≥ 1000 mL). Due to 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 Dutch women with VWD were prospectively enrolled (2018-2024). VWF/FVIII activity levels and hematologic and obstetric outcomes were compared with those of a historical cohort (2012-2017). Statistics included descriptives and logistic regression to correct for confounders. Results Severe PPH occurred in 18.1% (n = 29/160) without thrombosis or exsanguinations. Prophylaxis in those with third trimester levels of ' 80 IU/dL led to PPH rates similar to those with spontaneous a rise ' 80 IU/dL. Compared with the historical cohort (prophylaxis cutoff, ' 50 IU/dL), severe PPH incidence did not decrease (n = 20/151 vs n = 29/160; odds ratio [OR], 1.45; 95% CI, 0.78-2.69). Moreover, in the third trimester 50- to 80-IU/dL subgroup and third trimester ' 50-IU/dL subgroup, the risk for severe PPH was similar (n = 31/160 vs n = 23/151; OR, 0.86; 95% CI, 0.23-3.28; and n = 64/160 vs n = 48/151; OR, 2.59; 95% CI, 0.78-8.60, respectively), despite increased peak target levels of 150 IU/dL. Conclusion Increasing the third trimester VWF and FVIII cutoff to ' 80 IU/dL and aiming for ≥ 150 IU/dL at delivery did not decrease severe PPH. More research is needed on optimal peripartum hemostatic prophylaxis in VWD.