Impact of Tranexamic Acid on Postpartum Hemorrhage in Type 1 von Willebrand Disease Treated with Recombinant VWF

Postpartum hemorrhage (PPH) affects up to 44% of women with von Willebrand disease (VWD) despite recombinant VWF (rVWF) treatment. As tranexamic acid (TXA) reduced PPH-related deaths in the WOMAN trial, we assessed whether TXA combined with rVWF versus rVWF alone prevents PPH in VWD. VWD-Woman, a phase 3, open-label, randomized pilot trial, enrolled pregnant women ≥18 years with VWD (VWF:RCo <0.50 IU/mL, bleeding history). Participants received intravenous rVWF 80 IU/kg at delivery and postpartum days 1 and 2, with or without TXA (1g within 3 hours of delivery). The primary outcome was quantitative blood loss (QBL) at delivery. Secondary outcomes included 21-day pictorial blood assessment chart (PBAC) scores, hemoglobin changes, transfusions, hysterectomy, and safety. (NCT04344860) Of 103 screened, 40 were eligible, and 20 were enrolled (10 per group), 100% of whom were iron deficient. Mean QBL was similar (TXA + rVWF: 727·0 mL [95% CI: 434·5, 1019·5] vs. rVWF: 539·7 mL [95% CI: 132·8, 946·6]; p=0·41), as were rates of PPH (30% in both groups). No significant differences were observed in hemoglobin change (-1·90 g/dL vs. -1·42 g/dL, p=0·49) or 21-day cumulative PBAC score (467·1 vs. 344·8, p=0·32). Stratified analyses showed no significant differences by age, BMI, VWF activity, or delivery type. No serious adverse events or thrombosis occurred. TXA plus rVWF is feasible and safe in type 1 VWD, but in this small pilot study, was not associated with a reduction in PPH compared to rVWF alone. Iron deficiency is prevalent but underrecognized. Further studies are needed to improve PPH prevention in VWD.