Clinical Use of a Von Willebrand Factor with a Low FVIII Content in Von Willebrand Disease Patients Undergoing Surgical Procedures or Deliveries: Results From 5 Prospective Multicenter Studies

Von Willebrand disease (VWD), the inherited bleeding disorder is related to a quantitative or functional defect of von Willebrand factor (VWF). As VWF serves as a carrier for factor VIII (FVIII) in plasma, some VWD types involve low FVIII binding and thus low FVIII levels. International consensus confirms that VWF:RCo is the main predictor in controlling bleeding from mucous membranes in VWD patients. On the other hand, it is recognized that FVIII is the main factor involved in surgical hemostasis. Conversely, high levels of FVIII may increase thrombogenic risk. Thus, the management of surgical procedures in all VWD types needs to be evaluated in terms of coadministration of exogenous FVIII. We report the efficacy and safety of a high purity plasma-derived, triple-secured, VWF concentrate with a low FVIII content (WILFACTIN/ WILLFACT) in preventive treatment of bleeding during surgical procedure and delivery in patients when desmopressin treatment alone is ineffective or contra-indicated.

Five prospective multicenter studies including one post-marketing study were conducted between January 1999 and July 2009. Data from 4 completed prospective multicenter studies and data from one interim analysis were pooled and analyzed. The investigators were asked to assess efficacy according to the clinical response at time of hospital discharge.

One hundred and forty one patients (51 males, 90 females) with a mean age of 35 years (1–84) and body weight of 66 kg (10–120) underwent 215 procedures (206 surgeries and 9 deliveries by natural route). A total of 52 (37%) patients had basal FVIII:C levels <20% whereas 43 (30%) had >40%: 29 patients (21%) had type 1 VWD; 81 (57%), type 2; 27 (19%), type 3; and 4 (3%), unspecified. Dental procedures (54) represented a quarter of the procedures. Others were gyneco-obstetrical (45), orthopedic (37), digestive (35), general (28) and other location (16). As shown in Table 1, baseline FVIII levels were corrected before surgery if necessary, in 155/214* (72 %) of the procedures, either by capturing natural FVIII activity after a 12–24 h lag-time post VWF infusion (83 procedures) or by FVIII concentrate co-administered with WILFACTIN/ WILLFACT (72 procedures). The VWF concentrate was always administered alone after the procedure, due to enhanced stabilization of endogenous FVIII.

For type 3, the median daily dose and mean number of infusions, including post-surgical prophylaxis, were 55 IU/kg and 6.0 respectively, while for type 1 and 2, the median daily dose was 47 and 53 IU/kg respectively and 4 infusions. Hemostatic efficacy was rated as excellent (114) or good (29) in 99% of evaluated procedures (n=144). Fifteen patients received packed red cells in addition to the concentrate. The overall tolerability was very good; neither VWF inhibitor nor thrombotic complications were reported.

Based on prospective studies conducted in a large cohort of European patients (N=141), a VWF with a low FVIII content (WILFACTIN/WILLFACT) was shown to be effective and safe for the clinical management of patients with various types of VWD administered for surgical prophylaxis and delivery.

No relevant conflicts of interest to declare.