Have you ever had a nosebleed or a cut that felt like it just wouldn’t stop bleeding? Von Willebrand disease (vWD) is the most common inherited bleeding disorder that is involved with hemostasis, or the ability to stop blood flow. Von Willebrand disease gets its name from the Von Willebrand factor (VWF), which is a glycoprotein in blood that has implications in platelet aggregation to the subendothelial tissue. More concisely, VWF allows for platelets to collect at the site of an injury, leading to a thrombus which blocks blood flow. VWF also binds to coagulation factor VIII in the blood, which doesn’t allow for factor VIII to be degraded. This helps facilitate clotting. Following an injury, both endothelial cells and platelets secrete VWF, which binds to collagen and initiates a conformational change. This change exposes the A1 binding site to which circulating platelets in the blood bind to and create platelet adhesion. This structure (platelets adhered to VWF) moves along the endothelium until it is able to bind, aggregate, and form a platelet plug which blocks blood flow.
There are three main subtypes of von Willebrand disease – types
1, 2, and 3. The type of vWD is determined by measuring the amount of VWF in
the blood. The less VWF present, the more severe the disease. Type 1 is
characterized by partial deficiency in VWF and is the mildest version. Type 2
has significant defects in VWF, and type 3 has an almost complete deficiency of
VWF. Patients with mild versions of vWD may be asymptomatic and unaware of
their condition. The prevalence of symptomatic von Willebrand disease is much
lower, at about 0.1%. Most patients who have von Willebrand disease have mild/minimal
symptoms, including nosebleeds, gingival bleeding, heavy menstrual bleeding, or
hemorrhage following surgery or childbirth. As you can imagine, some patients
may never be in these situations, thus, VWD may go undiagnosed. Rarer subtypes
of the more severe forms of this disease can cause life-threatening bleeding.
Though VWD can be inherited through a family history of
bleeding disorders, it can also be acquired secondary to underlying conditions.
For example, having hypothyroidism or taking valproic acid can cause reduced
synthesis of VWF. The clinical manifestation of both versions of von Willebrand
disease are virtually identical. It is important for healthcare professionals
to consider the possible downstream effects of any condition or treatment and
look at a patient holistically.
Swami, A. & Kaur, V. (2017). von Willebrand disease: A
concise review and update for the practicing physician. Clinical and Applied
Thrombosis/Hemostasis, 23(8), 900-910. https://doi-org.dml.regis.edu/10.1177/1076029616675969.
Echahdi, H., El Hasbaoui, B., El Khorassani, M., Agadr, A.
& Khattab, M. (2017). Von Willebrand's disease: case report and review of
literature. PanAfrican Medical Journal, 27(147), 1-7. doi:10.11604/pamj.2017.27.147.12248.
Fantastic article! The masters of biomedical students learned a good bit about blood coagulation this semester and the importance of von Willebrand Factor in forming a platelet plug by binding to the sub-endothelial proteins and to a platelet receptor, allowing platelets to adhere and form a plug. Once the platelet receptor binds to the connective tissue of the sub-endothelium, they release chemical mediators from the platelet granules like prostaglandins for vasoconstriction and ADP to recruit additional platelets. Patients with severe COVID-19 often suffer with blood coagulation and fatal thrombosis and can develop acquired von-Willebrand syndrome (Hayakawa et al., 2021). Patients presenting with these symptoms are prescribed cryoprecipitate for treatment as cryo is a highly concentrated source of fibrinogen, a soluble plasma glycoprotein that is converted to fibrin by thrombin, and stabilizes the platelet plug (Hayakawa et al., 2021).
ReplyDeleteHayakawa, M., Takano, K., Kayashima, M., Kasahara, K., Fukushima, H., & Matsumoto, M. (2021). Management of a COVID-19 Patient during ECMO: Paying Attention to Acquired von Willebrand Syndrome. Journal of atherosclerosis and thrombosis, 28(4), 396–401. https://doi.org/10.5551/jat.58362
Such a creative title! I haven't heard of Von Willebrand Disease before probably since only 1% of the population is affected by it. Unlike most inherited disorders, this one has treatments and isn't life threatening! Treatments can include Desmopressin, infusions, and birth control pills. Desmopressin can be used to treat type 1 and type 2 VWD or for acute bleeding by releasing stored VWD factor. This treatment is not given to those who are above 70 or below age 2 since it can cause an imbalance of water to salt resulting in seizures and coma (Sabih et al., 2022).
ReplyDeleteSabih, A., & Babiker, H. M. (2022). Von Willebrand Disease. In StatPearls. StatPearls Publishing.