Pregnant women with von Willebrand Disease (VWD) receive prophylactic von Willebrand factor (VWF) concentrate based on third-trimester VWF/FVIII 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 IU/dL to <80 IU/dL, and peak target levels during childbirth from ≥100 IU/dL to ≥150 IU/dL.

Pregnant Dutch women with VWD were prospectively enrolled (2018-2024) to assess the severe PPH incidence after guideline revision. VWF/FVIII activity levels, hematologic and obstetric outcomes were compared to a historical cohort (2012-2017). Statistics included descriptives and logistic regression to correct for confounders.

Severe PPH occurred in 18.1% (n=29/160)without thrombosis or exsanguinations. Prophylaxis in those with third trimester levels <80 IU/dL led to PPH rates similar to those with spontaneous a rise >80 IU/dL. Compared to the historical cohort (prophylaxis cut-off <50 IU/dL), severe PPH incidence did not decrease (n=20/151 vs. n=29/160, OR 1.45 95%CI 0.78-2.69). Also in the third-trimester 50-80 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.

Increasing the third-trimester VWF and FVIII cut-off 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.