Children with Severe Von Willebrand Disease May Benefit from Treatments with Plasma Factors

Researchers reviewed the use of high-purity concentrates containing two plasma molecules that are lacking in patients with Von Willebrand disease (VWD), a hemorrhagic disorder. These products may be a good strategy for managing pediatric patients with VWD and hemophilia A (HA) who do not respond to other treatments.

The study, “Human Von Willebrand Factor/Factor VIII Concentrates In The Management Of Pediatric Patients With Von Willebrand Disease/Hemophilia A,” published in the journal Therapeutics and Clinical Risk Management, was conducted by Giancarlo Castaman and Silvia Linari with Careggi University Hospital in Florence, Italy.

Von Willebrand (VWD) disease is a common, inherited hemorrhagic disorder that results from a mutation in the gene that codifies a protein called von Willebrand factor (VWF). Normally, this protein circulates in the blood and serves two purposes: helping platelets adhere to sites where the blood vessel has been injured, and acting to bind and stabilize the procoagulant protein factor VIII (FVIII). Mutated VWF, however, impairs the proper interaction between platelets and the vessel wall, interfering with hemostasis (the process that causes bleeding to stop).

To date, two main therapies are available for patients with this disorder. One consists in the administration of desmopressin (DDAVP), which promotes the release of VWF from endothelial cells. The other is the administration of VWF/FVIII concentrates, providing the two factors that help regulate hemostasis in the patients.

DDAVP is free of risk of viral transmission and inexpensive, and works to increase FVIII and VWF blood levels by three to five times by releasing these factors from storage sites in the cells of the vessel wall. It is indicated for the treatment of patients with type 1 VWD, in which VWF and FVIII levels are higher than 10 U/dL, provided these factors are available in storage in normal levels. Patients with a more severe form of VWF disease (type 3 VWD) lack these factors in storage compartments, making DDAVP treatment useless.

Most VWF/FVIII concentrates available are plasma-derived and depend on plasma donor availability. Because they are given from one person to the other, there is some possibility of transmission of blood infection. However, a recombinant (produced in a laboratory) VWF concentrate has been approved by the FDA with the brand name Vonvendi (vonicog alfa, marketed by Baxalta US) for the treatment and control of bleeding episodes in adults with VWD. The production of this concentrate involves several different steps that, together, contribute to the safety of the final product.

“The VWF/FVIII concentrates play a key role in the management of pediatric patients,” the authors concluded. “They are the treatment of choice for patients with type 3 and type 2B VWD and severe/intermediate patients in whom [DDAVP] does not work or is contraindicated.”

“Although recombinant concentrates may represent the treatment of choice in children with HA, the VWF/FVIII concentrates may offer an advantage in the success of previously failed ITI [immune tolerance induction] with recombinant FVIII,” they added.