Von Willebrand Disease
Von Willebrand’s disease or vWD is a hereditary deficiency or abnormality of the blood protein von Willebrand factor, which affects platelet function. In simple terms, it is an inherited disorder that affects the blood’s ability to clot properly. “The most frequent defects in homeostasis are a prolonged bleeding time, decreased platelet adhesiveness, and low plasma concentrations of factor VIII and von Willebrand factor” (Wyngaarden, JB, 1992). The von Willebrand factor is found in plasma, platelets, and the walls of blood vessels.
When the factor is missing or defective, platelets cannot adhere to the vessel wall at the site of an injury. As a result, bleeding does not stop as quickly as it should. Credit is given to Dr. Erik von Willebrand, who first described the condition in 1926. As a group, bleeding disorders are rare. Von Willebrand disease is the most common inherited bleeding disorder, affecting as much as 1% of the population or more. Clinical Manifestations The main manifestation of vWD is a mucocutaneous hemorrhagic syndrome; however, vWD is characterized by an important clinical and biological heterogeneity.
Its transmission is autosomal, usually dominant (Boehlen F, 2007). vWD has a broad spectrum of clinical and laboratory features. It can range from a severe hemorrhagic disorder, in which the levels of Factor VIII is low enough and the bleeding problems severe enough that the disease must be differentiated from the classic hemophilia. (Wyngaarden, JB, 1992) Often, a person with von Willebrand’s disease has a parent who has a history of bleeding problems. Typically, a child bruises easily or bleeds excessively after a cut, tooth extraction, or surgery. A woman may have increased menstrual bleeding.
Bleeding may worsen at times. On the other hand, hormonal changes, stress, pregnancy, inflammation, and infections may stimulate the body to increase production of the von Willebrand factor and temporarily improve the capacity of platelets to stick to the blood vessel wall and stop bleeding. In others, epistaxis maybe the presenting illness. Diagnosis Laboratory tests typically show that the bleeding time it takes for blood to clot is abnormally long. Bleeding time is the amount of time that elapses before bleeding stops after a small cut is made on the forearm.
Bleeding time is the amount of time that elapses before bleeding stops after a small cut is made on the forearm. Doctors may order tests that measure the amount of von Willebrand factor in the blood. Because the von Willebrand factor is the protein that carries an important clotting factor (factor VIII) in the blood, the level of factor VIII in the blood may also be decreased. There are three major types of VWD. Type 1 vWD have low level of the von Willebrand factor, and you may have lower levels of factor VIII than normal.
This is the mildest and most common form of the disease. In Type 2 vWD, the von Willebrand factor doesn’t work the way it’s supposed to. Type 2 is divided into subtypes: 2A, and 2B. Different gene mutations cause each type, and each is treated differently. This is why, determination of type 2 is important since the treatment for each is different from each other. In Type 3 vWD, the is no von Willebrand factor and have low levels of factor VIII. Type 3 is the most serious form of VWD, but it’s very rare.
The tests to diagnose vWD may include: bleeding time, factor VIII level test which measures the level of factor VIII and its ability to function, von Willebrand factor antigen test which measures the amount of von Willebrand factor (vWf) ristocetin cofactor activity test which measures how well the von Willebrand factor is working (De Vleeschauwer A 2006), von Willebrand factor multimers test which helps classify the type of vWD, platelet function tests which determine how well the platelets work and help identify the type of vWD or the presence of another disorder (Wyngaarden, JB, 1992).
Treatment Technically, in treating Types 1 and 2 vWD, there should be replacement of the deficient protein at the time of spontaneous bleeding or before any invasive procedures are performed. The main therapy is Desmopressin, a synthetic derivative of antidiuretic hormone that acts through type 2 vasopressin receptors and is nearly devoid of activity through type 1 receptors. This induces secretion of autologous factor VIII and vWf into plasma.
The advantages of using desmopressin as a therapeutic agent are its relatively low cost and unlimited availability and the fact that plasma concentrates can be avoided. The most likely mechanism by which desmopressin increases von Willebrand factor is through cyclic adenosine monophosphate signaling to mediate secretion from Weibel–Palade bodies in endothelial cells into plasma (Mannucci PM, 2004). Another therapy mode is the use of plasma concentrates containing vWf with or without factor VIII. Adjuvant therapies include fibrinolysis inhibitors, oral estrogen-progesteron preparations and platelets.
Prophylaxis should be contemplated in patients with type 3 disease who have had recurrent hemorrhages in the joints or in the gastrointestinal tract. Conclusion Major advances in our understanding of the pathophysiology, molecular basis, and management of von Willebrand’s disease has been accomplished in the last 2 decades of vWD study. “The main options that are available for treatment (desmopressin and plasma concentrates) are effective in controlling bleeding in most patients with the disease.
Even though virus-inactivated products appear to have an acceptable level of safety, it is hoped that the von Willebrand factor that is produced by recombinant DNA techniques will soon undergo clinical trials and become available for replacement therapy” (Mannucci PM, 2004).
Boehlen F, Robert-Ebadi H, de Moerloose P, Von Willebrand disease: a common and unrecognized bleeding disorder, Rev Med Suisse. 2007;3(97):346-50 De Vleeschauwer A, Devreese K.Comparison of a new automated von Willebrand factor activity assay with an aggregation von Willebrand ristocetin cofactor activity assay for the diagnosis of von Willebrand disease, Blood Coagul Fibrinolysis. 2006;17(5):353-8 Mannucci PM. Treatment of von Willebrand’s disease. N Engl J Med. 2004;351:683-94. Free Full Text available at http://content. nejm. org/cgi/content/full/351/7/683? ijkey= 88683ba626d661645e82acef77b20d180b648a14&keytype2=tf_ipsecsha Wyngaarden, JB, Smith LH and Bennett JC, Cecil Textbook of Medicine: Disorders of Blood Coagulation, 19th Ed. , W. B. Saunders, 1992: p1006-7Sample Essay of Eduzaurus.com