Definition
A rare hereditary coagulopathy of genetic origin, characterised by a platelet adhesion defect and a secondary haemostasis defect manifested by abnormal bleeding of varying severity occurring either spontaneously or in association with invasive procedures. There are three main subtypes depending on the type of von Willebrand factor defect: partial (type 1) or total (type 3) deficiency, and qualitative/functional abnormalities (type 2).
Summary
Epidemiology
Depending on the study, the prevalence of von Willebrand disease (VWD) in the general population is estimated to be between 0.6% and 1.3% (all forms combined), but the prevalence of symptomatic VWD requiring specific treatment is around 1/10,000. Type 3 von Willebrand disease is much rarer (1/1,000,000).
Clinical description
The age of onset varies, with earlier onset associated with more severe VWF deficiency. The disease manifests itself as abnormal bleeding of varying severity, occurring either spontaneously or in association with an invasive procedure. Coagulation anomalies are characterised by mucocutaneous haemorrhage (epistaxis, menorrhage, bleeding from minor wounds, etc.), but haematomas and haemarthrosis may occur in the most serious forms.
Etiology
The disease is caused by mutations in the VWF gene (12p13.3) which codes for VWF, a multimeric protein. Intraplatelet, endothelial and plasma VWF is essential for the interaction of blood platelets with the damaged vascular wall and for the transport and survival of factor VIII (FVIII).
Diagnostic method(s)
Diagnosis is based on biochemical tests, i.e. immunological and functional assays of VWF and FVIII levels. Characterising the type of Willebrand disease requires highly specialised tests, such as a study of the distribution of VWF multimers.
Differential diagnosis(es)
Determination of VWF levels (antigen and function) can generally distinguish von Willebrand disease from haemophilia A. However, these tests cannot differentiate type 2N von Willebrand disease, which requires a specialised test. The differential diagnosis between acquired von Willebrand syndrome (AVWS), which occurs in association with another underlying pathology, and hereditary von Willebrand disease is more problematic. The differential diagnosis must also take into account the fact that individuals from the general population with blood group O may also have moderately lower VWF levels.
Prenatal diagnosis
In high-risk pregnancies, identification of the underlying VWF mutations can be used to make a prenatal diagnosis of type 3 von Willebrand disease.
Genetic counselling
The mode of transmission is autosomal, most often dominant; type 3 and a few cases of type 2 are recessive. Genetic counselling is offered to patients to inform them about the severity of the disease and its risks, and to identify family members likely to be affected. For couples likely to have a child with type 3, genetic counselling can be discussed in an approved multidisciplinary structure.
Care and treatment
Treatment depends on the type of disease. In type 1, the preventive or curative treatment of abnormal bleeding involves desmopressin, which is generally effective. In type 2, the response to desmopressin is variable, often necessitating replacement therapy with purified human Willebrand factor. In type 3, where desmopressin is still ineffective, treatment is replaced by purified human Willebrand factor combined with factor VIII, at least for the first injection.
Prognosis
Treatment in a hospital haemostasis clinic ensures a favourable prognosis, even in the most serious forms.
Willebrand’s disease is an HCM whose description is available on the ORPHANET portal for rare diseases and orphan drugs by clicking on the following link:
www.orpha.netOr visit the MHEMO website by clicking on the following link:
mhemo.fr
