Substitution Treatment of von Willebrand Disease with vWF and FVIII Concentrates

Substitution Treatment with Factor Concentrates and Its Indications

Substitution therapy in patients with vWD is based on the intravenous administration of concentrates containing coagulation factor VIII and von Willebrand factor or just vWF. FVIII concentrates without vWF are not effective in congenital vWD (perhaps with the exception of some cases with the presence of anti-vWF alloantibodies). vWF and FVIII concentrates differ in the quantitative ratio of vWF to FVIII and also in the amount of large multimers of vWF. Their dosage and clinical effect are therefore not identical.

These concentrates can be used both in the treatment and prevention of bleeding – spontaneous and traumatic. They can be administered regardless of age, in severe forms of vWD (especially type 3), but also in some patients with vWD type 2 or in cases of prolonged need for effective hemostasis in patients with vWD type 1. They are also used in this group of patients in case of an inadequate response to the administration of the synthetic analogue of antidiuretic hormone, i.e., desmopressin (DDAVP).

Dosage of Concentrates

The dosage of FVIII/vWD concentrates is based on the content of vWF:RCo and FVIII:C per unit (IU). The application of 1 IU vWF:RCo per 1 kg of body weight increases vWF activity by an average of 1.5%. Similarly, the administration of 1 IU FVIII per 1 kg of body weight increases its activity by 2%. The dosage and frequency of administration depend on the type of bleeding and the time required for wound healing. Substitution therapy usually continues until the wound heals, although some invasive procedures only require a single dose of concentrate before the procedure (see table). 

Table. Average doses of FVIII/vWF concentrates for prophylaxis and treatment in patients with severe factor deficiency (vWF activity < 10 IU/dl and/or FVIII:C < 20 IU/dl)

Monitoring Efficacy and Safety in Treatment Management

The efficacy of treatment should be monitored by measuring vWF and FVIII activities (although factor activity checks are not necessary for single-dose administration). Before surgery, it is advisable to measure FVIII and vWF levels approximately 30 minutes after concentrate administration. Prolonged administration of vWF/FVIII concentrates leads to FVIII accumulation in the plasma, as its half-life gradually extends.

Thromboembolic events associated with high FVIII activity have been described. Therefore, it is recommended to avoid prolonged levels of vWF:RCo and FVIII:C > 150%, especially in patients with a higher risk of thrombosis. Additionally, the consideration of antithrombotic prophylaxis is necessary.

The excessive rise in FVIII levels can be limited by administering concentrates with a vWF: FVIII ratio > 2:1. The gold standard for all types of vWD is a concentrate with a ratio of 2.4:1. The content of high molecular weight vWF multimers is comparable to that in plasma.

Recombinant vWF

A recombinant vWF concentrate is also available in Europe, approved for the treatment of bleeding and perioperative prophylaxis in adult patients with vWD. This preparation rapidly increases vWF activity in the plasma, followed by a slow rise in vWF activity. For this reason, urgent surgical procedures are usually ensured by administering the recombinant vWF concentrate alongside FVIII concentrate.

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Source: Zdziarska J., Chojnowski K., Klukowska A. et al. Management of von Willebrand disease. Recommendations of the Hemostasis Group of the Polish Society of Hematology and Transfusiology. J Transfus Med 2022; 15 (2): 75–99, doi: 10.5603/JTM.2022.0009.