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

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.