Replacement therapy in pregnant women with von Willebrand disease during delivery: Factor levels and pharmacokinetics

Limited data are available on VWF activity (VWF:Act) and factor VIII (FVIII:C) levels during delivery after VWF/FVIII concentrate administration in women with von Willebrand disease (VWD). We aimed to evaluate treatment with a specific VWF/FVIII concentrate on factor levels in women with VWD during delivery and the postpartum period. A retrospective single-center study was conducted between January 1, 2008, and August 1, 2022. Pregnant women treated with Haemate®P during delivery were included if they had ≥2 consecutive VWF:Act and FVIII:C measurements post-infusion. VWF:Act/FVIII:C levels were compared to predefined target levels. A population pharmacokinetic (PopPK) model was developed, estimating VWF and FVIII pharmacokinetics after Haemate®P administration. Nineteen women were included. Targeted VWF:Act/FVIII:C peak levels were achieved after the first infusion (≥1.00 IU/mL, n = 12; ≥1.50 IU/mL, n = 5), and all VWF:Act/FVIII:C trough levels remained ≥0.50 IU/mL during first 72 h of treatment. All women had pretreatment FVIII:C levels ≥1.00 IU/mL, except one woman with type 2N, which was significantly higher than FVIII:C levels during the third trimester (median increase: 0.42 IU/mL, interquartile range: [0.12–0.92]). FVIII:C trough levels increased during treatment, median 2.05 IU/mL [1.65–2.71]. Nine women (47%) experienced postpartum hemorrhage and no thrombosis occurred. A one-compartment PopPK model adequately described VWF:Act/FVIII:C levels. Targeted VWF:Act/FVIII:C peak levels were achieved with the prescribed dosing regimens. VWF clearance was similar to that in nonpregnant individuals. Both pretreatment and FVIIIC trough levels during treatment were high with reduced FVIII clearance. Monitoring VWF:Act/FVIII:C levels is recommended for optimizing target levels and enriching the current PopPK model, improving VWF:Act/FVIII:C level predictions, and achieving more effective dosing.