Von Willebrand disease (VWD) is relative to an abnormality, either quantitative or qualitative, of von Willebrand factor (VWF). Among patients with severe VWD, pregnant women are at increased risk of bleeding especially for the peripartum period both for vaginal delivery and Caesarean section. In patients with type 3 VWD and in patients with a functional defect, the treatment with VWF is required for the prevention of bleeding during the delivery. Predisposition towards an increased risk of thrombosis in pregnant women is well establish and this predisposition to thrombosis results from the hypercoagulable state of pregnancy with increased factor VIII and VWF levels. As endogenous factor VIII production in patients with VWD is intact, the treatment with a VWF concentrate with a low factor VIII content provides hemostatic levels of factor VIII, by stabilization of endogenous factor VIII, while providing efficient primary hemostasis. We report the efficacy and safety of Wilfactin, a triple-secured VWF concentrate almost devoid of factor VIII, for the preventive treatment of bleeding during the delivery period.
Data from 4 prospective multicenter studies including one fully monitored post-marketing study were pooled. As recommended in the protocols, if needed, the unscheduled childbirth was managed by VWF with the coadministration of factor VIII at the first infusion. When time permitted, two infusions of Wilfactin were administered: one at 12–24 hours and one 30 minutes-1 hour prior to childbirth. The investigators were asked to evaluate the efficacy on a 4-point scale (Excellent, Good, Moderate, None) at the end of treatment.
Across all studies, 22 VWD women delivered 24 children. Wilfactin was used to prevent bleeding in 9 vaginal deliveries in 9 women (3 type 1, 5 type 2 and 1 type) and 15 Cesarean deliveries in 13 women (3 type 1, 9 type 2 and 3 type 3). There were no notable differences in the evaluation of efficacy between vaginal and Caesarean deliveries. The efficacy was rated as ‘good/excellent’ in 20 of 21 (95%) evaluated deliveries and ‘moderate’ in one cesarean due to a moderate, but controlled bleeding. Blood transfusion was required for a retroplacental hematoma in one Cesarean section but the efficacy of the product was rated as excellent by the investigator. Over the total course of therapy for childbirth, the median dose per infusion was higher for vaginal delivery (42 IU/kg) than for Cesarean section (27 IU/kg). Women received more infusions for Cesarean section than for vaginal delivery (15 vs 8) and more treatment days (10 vs 6, respectively) but, the total dose per type of treatment was quite similar (374 vs 272 IU/kg). A priming dose of factor VIII at the first infusion of Wilfactin was given to ensure rapid coagulation before starting 5 Cesarean sections and 4 vaginal deliveries. For 4 other Cesarean sections, the hemostatic level of factor VIII was achieved by an initial infusion of Wilfactin 12 to 24 hours before the procedure. No special measures to increase factor VIII were required for the other 11 deliveries. The overall tolerability was very good; neither VWF inhibitor nor thrombotic complications were reported. An additional data is to note that 2 patients were treated with long-term prophylaxis regimen during pregnancy because of placental hematoma.
Good hemostatic efficacy, absence of thrombotic or other severe complications shown in the clinical trials with Wilfactin are encouraging for its use in the management of pregnant VWD women for vaginal delivery or Cesarean section.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.