Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Most cases are transmitted as an autosomal dominant trait, although with variable penetrance.
There are three major types of VWD disease. Type 1, the most frequent form, is characterised by a partial quantitative deficiency in von Willebrand factor (VWF). Type 2 is a qualitative deficiency, and type 3 is a virtually complete deficiency. Type 2 VWD is divided into four subtypes. Type 2A includes variants with decreased platelet adhesion caused by a selective deficiency in high-molecular weight VWF multimers (HMWM). Type 2B includes qualitative VWF variants with an increased affinity to platelet glycoprotein Ib. Type 2M includes variants with decreased platelet adhesion, but without HMWM deficiency, and type 2N includes variants with markedly decreased affinity for factor VIII. This categorisation correlates with therapeutic requirements.
VWF is a plasma glycoprotein produced in megakariocytes and endothelial cells. It plays an important role in primary haemostasis through the mediation of initial platelet adhesion to sites of vascular injury. It also binds and stabilises factor VIII (FVIII) in the blood.
VWD diagnosis, especially type 1, may be difficult. In mild cases, VWF levels may overlap with those of normal subjects. The clinical manifestations of the disease may vary from minimal to severe. However, the bleeding risk generally parallels VWF levels. Given that a mild decrease of VWF levels is relatively common, the prevalence of the disease varies among studies and can be as high as 1% in the general population. As a consequence, only a fraction of patients come to medical attention because of bleeding symptoms. A definite diagnosis of VWD type 1 is performed when VWF:Ag is < 30 IU/dL, in association with bleeding symptoms. Persons with VWF:Ag levels of 30-50 IU/dL are considered to have a low VWF level, but not a VWD. They may also be at risk of bleeding. During the pre-operative evaluation of those patients, the presence of bleeding symptoms should always outweigh the VWF levels in assessing the bleeding risk. Among the signs that should draw the attention of the practitioner, the most common are recurrent and prolonged nosebleeds, bleeding from the gums, increased menstrual blood losses, excessive bleeding from a cut or following a tooth extraction, easy bruising, and family history.