Von Willebrand factor is a protein that plays a critical role in blood clotting. Deficiency of the clotting factor results in unstoppable bleeding.
What is von Willebrand factor?
Von Willebrand factor was named after the Finnish internist Erik Adolf von Willebrand. He described in his Swedish paper Heredität pseudohemofili the clinical picture of a hereditary blood clotting disorder. This was later named after him Von Willebrand syndrome. It was not until the 1950s that it was discovered that a deficiency in a protein that shortens bleeding time was the cause of Von Willebrand syndrome. Subsequently, this protein was named Von Willebrand factor. Von Willebrand factor has a direct effect in hemostasis. Although its direct effect is limited exclusively to cellular hemostasis, plasmatic coagulation is also affected. When Von Willebrand factor is deficient, hemostasis is impaired. Von Willebrand disease, often referred to as Willebrand-Jürgens syndrome, is the most common inherited hemophilia worldwide. An estimated 800 out of 100000 people are affected. However, only two percent have significant symptoms.
Function, effects, and roles
Von Willebrand factor is the carrier protein of blood clotting factor VIII. Clotting factor VIII is the antihemophilic globulin A. Together with factor VIII, Von Willebrand factor circulates in the blood. By forming a complex, the coagulation factor is protected from proteolysis, i.e. the degradation of proteins. In the body, Von Willebrand factor can bind to the Von Willebrand receptor. This receptor, which consists of glycoprotein Ib/IB, is located on the surfaces of blood platelets (thrombocytes). Von Willebrand factor can also attach to the proteins of the so-called subendothelial matrix. The subendothelial matrix is located just below the half of the uppermost layer of the inner lining of the blood vessel. In case of injury, the Von Willebrand factor can thus adhere to the proteins or to the platelets. Thus, it acts as an adhesive protein and creates a link between the platelets and the injury. Thus, Von Willebrand factor activates primary hemostasis. The platelets adhere to the fibers of the injured vessel wall, forming a thin mesh over the wound. Subsequently, the platelets release various substances that attract further platelets by means of chemotaxis. At the same time, these substances cause the affected blood vessel to constrict and allow less blood to escape. The activated platelets aggregate and form a plug that temporarily closes the wound. This process of initial hemostasis is called cellular or primary hemostasis.
Formation, occurrence, properties, and optimal values
Von Willebrand factor is produced by megakaryocytes and by endothelial cells of the inner wall of blood vessels. Megakaryocytes are giant cells found primarily in bone marrow. They are the precursor cells of platelets. The platelets are stubs of the megakaryocytes. They contain the Von Willebrand factor in their α-granules. The Von Willebrand factor system is measured in the blood with different values together with the values of factor VIII. Thus, the term vWF:Ag refers to the large-molecule and multimeric portion of the system. This fraction can be understood as the actual Von Willebrand factor. In addition, the vWF activity, for example, can be determined. The differentiation of the individual components plays a role in the diagnosis of diseases in which parts of the von Willebrand factor system are impaired. The reference value is 70-150% of the norm. The value depends on the blood group. Plasma concentration should be between 5 and 10 micrograms per liter.
Diseases and disorders
Elevated levels of Von Willebrand factor can be found in inflammation. The factor is a so-called acute-phase protein. These proteins localize inflammation, prevent it from spreading, and assist the body’s defense system in remediation. The Von Willebrand factor in the blood can also be elevated in rheumatic diseases, autoimmune diseases and cancer. Furthermore, taking the “contraceptive pill” can drive the value up. Decreased values are an indication of the presence of Von Willebrand-Jürgens syndrome.This common disorder of blood coagulation is associated with an increased tendency to bleed. Therefore, Von Willebrand-Jürgens syndrome belongs to the hemorrhagic diatheses. In the majority of cases, the cause of the disease is a hereditary disorder of the Von Willebrand factor system. The disease can be divided into different types. In type 1, there is a quantitative factor deficiency. 80 percent of those affected belong to this group. They usually show rather mild symptoms. However, long-lasting bleeding may occur, especially after surgery. In women, menstruation is increased and large hematomas form in the event of impact injuries. In type 2, although sufficient Von Willebrand factor is present, it is not fully functional. It is therefore a qualitative defect. Type 3 is the rarest form. However, type 3 patients also show the most severe course. The Von Willebrand factor is completely absent in type 3 or is reduced to less than 5 percent. The increased bleeding tendency results in frequent nosebleeds (epistaxis), extensive “bruising,” prolonged bleeding even after minor surgery, increased menstrual bleeding, and joint hemorrhage (hemarthrosis). In most patients with Von Willebrand-Jürgens syndrome, permanent therapy is not required. However, patients should avoid drugs containing acetylsalicylic acid. These further inhibit platelet function. Vasoconstrictive nasal sprays can be used for frequent nosebleeds. Increased menstruation can be treated with hormonal contraceptives with a higher progestin content. In type 3, these measures are not sufficient. Here, in most cases, factor is substituted for trauma. Prophylactic substitution at intervals of two to five days is also possible.
