Replacement Therapy in Patients with Von Willebrand Disease—Indications and Monitoring

Abstract

In patients with von Willebrand disease (VWD), replacement therapy may be indicated in the case of spontaneous bleeding, surgical interventions and injuries/trauma or as a prophylaxis of spontaneous bleeding episodes. The deficient von Willebrand factor (VWF) is replaced with or without factor VIII (FVIII). Dual VWF/FVIII concentrates can be beneficial in the case of low FVIII level, while repeated dosing may lead to very high FVIII levels, with a potential thrombogenic effect in individual VWD patients. An excessive FVIII:C increase can be limited by using a VWF product with a low level of FVIII, achieving a haemostatic adequate FVIII:C increase after 6 to 12 hours. Replacement therapy in patients with VWD shall be individualised considering VWD type, history and risk of bleeding and risk of thrombosis, as well as indication and the individually variable VWF and FVIII increase. Deviations from the dosages and minimum trough levels mentioned in guidelines or recommendations can be considered in justified cases. The objective of this review is to provide recommendations for specific constellations of replacement therapy based on the VWD-specific guidelines available in Europe, the available evidence, own experiences and the consensus of the interdisciplinary German author group.

The Cost of Von Willebrand Disease in Europe: The CVESS Study

“…One such factor may be differences in treatment practice; in several of these countries (such as Italy and Germany), there are no national VWD guidelines to follow. 41 However, the European guidelines state that prophylaxis dosing should be tailored to each patient based on their VWD severity, and risk of and tendency towards bleeding, which may account for some of the variation in bleeds, hospitalisations and treatment costs observed in CVESS. 42 When comparing the direct costs excluding VWF, we still see large differences in burden across countries, for example in the UK compared to France (€159 791 064 vs €39 175 872).…”

Von Willebrand Disease—Specific Aspects in Women

“…The risk of bleeding has been shown to be minimal when the FVIII activity (FVIII:C) and VWF:RCo levels were higher than 50%. 6 16 Therefore, measuring the parameters within the third trimester (∼32–34 weeks) and ahead of the expected date of delivery should be taken into consideration when considering the peripartal recommendations.…”

“…Spinal anesthesia (e.g., peridural anesthesia) should not be performed without adequate replacement therapy in women with antepartum VWF activity levels <50 IU/dL or in those patients with a history of severe bleeding. 16 19 39 43 Furthermore, VWF levels of >50 IU/dL should be maintained for the duration of the catheter placement and prior to the removal of the catheter.…”

“…Therefore, FVIII overload should be avoided, and the administration of VWF products in patients with a low or no FVIII content is prudent. 16…”

“…Since deficiencies of VWF are associated with pathological angiodysplasia and vascular malformations that account for GI angiodysplasia and bleeding, the predisposition for angiodysplasia accounting for recurrent miscarriage has been considered as well. 14 16 17 18 The treatment options for bleeding complications in patients with VWD include desmopressin (DDAVP), the administration of VWF concentrates including both plasma-derived and recombinant products, as well as antifibrinolytic therapy (e.g., tranexamic acid, TxA). 19 After giving DDAVP, the mobilization of stored VWF is achieved within 30 to 60 minutes to reach increased plasma FVIII and VWF levels, which usually last for 6 to 8 hours.…”