Introduction
Von Willebrand disease (vWD) can be defined as the most common hereditary coagulation abnormality depicted in humans, even though it can as well be acquired from other medical conditions. It occurs as a result of a quantitative or qualitative deficiency of von Willebrand factor (vWF), which is a multimeric protein needed for adhesion of platelet. It is recognized to affect humans as well as dogs, and on rare occasion cattle, swine, cats, and horses. There exist three types of vWD namely acquired, inherited and platelet or pseudo type.
Symptoms
In several individuals with von Willebrand disease vWD, the symptoms are mild, or they may be absent completely. When symptoms happen, their strength can differ from one individual to another. The disease is often pose challenges during diagnosis of milder cases.
The most common vWD symptom is abnormal bleeding, even though it may exist at just moderate degrees. The abnormal bleeding linked to vWD can happen as:
- Recurring and prolonged nosebleeds,
- Gum bleeding, raised menstrual flow,
- Excessive bleeding when one is cut or after an extraction of tooth or other dental surgery,
- Bloody stool or urine, and bleeding from shaving using a razor
Below (fig 1) are a number of pictures of persons presenting the symptoms of vWD.
Figure 1: A picture of symptoms of Von Willebrand disease1
The Von Willebrand disease affects the gums, lower portion of the digestive system, nose, and reproductive system among others2.
Genetics
The von Willebrand factor (VWF) gene mutations lead to the vWD. The VWF gene offers instructions for production of a blood clotting factor referred to as VWF that is crucial in the formation of blood clots. Following an injury, clots offer protection to the body through sealing off of damaged blood vessels as well as prevention of further loss of blood. VWF serves as a glue to hold clots of blood together and precludes other blood clotting proteins’ breakdown. Abnormal functioning or little availability of the VWF, blood clots are not able to form properly. Abnormally slow clotting of blood leads to the prolonged episodes of bleeding observed in vWD.
The three forms of vWD depend on the produced quantity of VWF. VWF gene mutations, which lower the amount of VWF result in type 1 von Willebrand disease. Individuals with type 1 have, in their bloodstream, differing amounts of VWF. Several individuals with a mild type 1 case never go through a prolonged episode of bleeding. Mutations, which interrupt the von Willebrand factor function, result in the type 2’s four subtypes. Individuals with type 2 von Willebrand disease experience bleeding episodes of different severity based on the degree of dysfunction of the von Willebrand factor, though the episodes of bleeding are characteristically the same as those observed in type 1. Mutations, which lead to an abnormally short, malfunctioning von Willebrand factor usually cause type 3 von Willebrand disease. Since there is no functional protein, individuals with type 3 von Willebrand disease normally have severe episodes of bleeding.
Von Willebrand disease may have varying patterns of inheritance. Type 1, as well as rare instances of type 2 von Willebrand disease, are acquired in an autosomal dominant pattern meaning that one copy of the modified gene in every cell is enough to cause the disease. Type 3 together with most type 2 cases are acquired in an autosomal recessive pattern, meaning that both copies of the gene in every cell have mutations. Most often, each parent of a person with an autosomal recessive condition carries a single copy of the gene that is mutated, although they do not exhibit the conditions’ signs, as well as symptoms.
Von Willebrand disease is named as a rare disease by the National Institutes of Health’s Office of Rare Diseases. This entails that the disease, or a subtype of it, affects below 200,000 individuals in the population of US. It affects males and females in an equal manner. A male or female with the disease has a 50% probability of transmitting the gene to his or her baby. There exist no racial or ethnic links with the disease. A family history of a disorder of bleeding is the basic risk factor3.
Detection/Diagnosis
When surmised, patient’s blood plasma requires to be examined for qualitative and quantitative vWF’s deficiencies. This is attained through measuring of the quantity of vWF in an assay of vWF antigen as well as the vWF functionality with a collagen binding assay, a glycoprotein Ib binding assay, or ristocetin induced platelet agglutination or a ristocetin cofactor activity assays. Factor VIII levels are as well carried out since factor VIII is bonded to vWF that offers protection to the factor VIII from fast breakdown in the blood. vWF Deficiency can, thus, cause a decrease in levels of factor VIII. Normal levels do not omit all types of vWD, especially type 2 that may just be disclosed through investigation of interaction of platelet with sub-endothelium under flow with platelet function assay (PFA), a highly specialized coagulation investigation. An aggregation assay of platelet will demonstrate an abnormal reaction to ristocetin with normal reactions to the other agonists employed. A PFA will produce an abnormal collagen/adrenaline time of closure and in the majority of cases a normal time for collagen/ADP. Type 2N can only be detected through carrying out a factor VIII binding assay. VWD detection is complicated because vWF is an acute phase reactant with levels increasing during pregnancy, stress and infection.
Other tests carried out in any suspected vWD patient are a complete blood count, thrombin and prothrombin time, activated partial thromboplastin time, as well as fibrinogen level. Factor IX testing may also be carried out if hemophilia B is surmised. Individuals with vWD will characteristically show a normal prothrombin time as well as a variable lengthening of partial thromboplastin time4.
Treatments
For vWD type 1 and vWD type 2A patients, desmopressin is prescribed for use in instances of minor trauma, or in readiness for minor surgical or dental procedures. Desmopressin triggers the production of vWF from the endothelial cells’ Weibel Palade bodies, thus raising the vWF levels 3 to 5-fold. For women experiencing heavy menstrual bleeding, oral contraceptive medications containing estrogen are effective in decreasing the rate and duration of the menstrual periods. Estrogen compounds for correction of menorrhagia are Levonorgestel and Ethinyl Estradiol. Ethinyl Estradiol administration decreases the secretion of follicle stimulating hormone and luteinizing hormone from the pituitary, resulting in stabilization of the uterine endometrial surface (Mayo Clinic staff, 2013). For vWD patients scheduled for operation and instances of vWD disease complicated by clinically significant hemorrhage, concentrates of human derived medium purity Factor VIII, which contain VWF, are available for treatment and prophylaxis.
Transfusions of blood are given as required for correction of anemia and hypotension secondary to hypovolemia. Platelet concentrates infusion is can be prescribed for correction of hemorrhage related to platelet-type vWD. The antifibrinolytic agents Tranexamic acid and Epsilon amino caproic acid are important adjuncts in the control of vWD with complications of clinical hemorrhage5.
Cited References
- National Health Service [internet]. von Willebrand disease. [Modified 2012; cited 2013Nov 19]. Available from: http://www.nhs.uk/conditions/von-willebrand-disease/Pages/Introduction.aspx
- National Heart Lung and Blood Institute. The diagnosis, evaluation, and management of von Willebrand disease. Bethesda: NIH; 2007.
- Ginsburg D, Bowie EJ. Molecular genetics of von Willebrand disease. Blood. 1992;79: 2507-2519.
- Favaloro EJ, Bonar R. Kershaw G. Reducing errors in identification of von Willebrand disease: the experience of the Royal College of Pathologists of Australasia quality assurance program. Semin Thromb Hemos. 2006;32(5): 505–513.
- Mayo Clinic staff [internet]. Von Willebrand disease. [Modified 2013; cited 2013 Nov 18]. Available from: http://www.mayoclinic.com/health/von-willebrand-disease/DS00903/DSECTION=treatments-and-drugs.
