## 4 Discussion
### Bleeding Diathesis from Disorders of Coagulation Factors
#### 4.7.2 Von Willebrand Factor Deficiency Disease  
[PERSON]'s disease (VWD) is an inherited bleeding disorder caused by a genetic defect resulting in a quantitative, structural, and/or functional abnormality of VWF.  
The disease is classified into three main groups, based on the VWF deficiency: the form with a partial quantitative defect (type 1); the form with a qualitative defect (type 2), which in turn is subdivided into different subtypes 2A, 2B, 2M, 2N; and the form with a total quantitative defect (type 3) [54].  
The overall prevalence of VWD is estimated between 0.1% and 1%, but the prevalence of symptomatic VWD, which requires specific treatment, is estimated to be between 1 per 50,000 and 1 per 8500. The disease onset is variable, being earlier in the most severe forms.  
Clinical symptoms include bleeding of varying degrees, which may arise spontaneously or during the use of invasive techniques. Mucocutaneous haemorrhages (epistaxis, menorrhaging, etc.) are the most common type of bleeding abnormality are usually characterized by but haematomas and hemorrhosis can also occur in the most severe cases [54].  
VWD is caused by mutations in the \(VWF\) gene (12p13.3), which encodes for the multimeric protein VWF. The VWF protein has an intra-platelet, endothelial, and plastic localization and plays an essential role both in the adhesion of platelets to the endothelium of the injured vessel and in the transport and stabilization of FVIII [54].  
VWD is mainly transmitted in an autosomal dominant manner; however, some subtypes of forms 2 and 3 have an autosomal recessive inheritance. The diagnosis is based on laboratory tests based on VWF and FVIII assays, using functional and immunoassay. The subclassification of VWD requires very specific tests, such as studying the distribution of VWF multimers. The VWF assay usually distinguishes VWD from haemophilia A. However, this test does not distinguish VWD type 2N, necessitating further investigation. More problematic is the differential diagnosis of acquired Von Willebrand syndrome, which is associated with other diseases, and hereditary VWD [55]. Notably, people with blood type 0 may have slightly lower VWF levels. Genetic counselling is recommended to inform patients of disease risks and to offer clinical and genetic screening to identify other affected family members. For couples at risk of having a child with type 3 form, genetic counselling should be performed at a specialized multidisciplinary centre [55]. Treatment depends on the VWD type. Specifically, desmopressin is usually effective in preventing or treating abnormal bleeding in type 1 VWD, but in patients with type 2 disease, replacement therapy with purified VWF is often required since the response to desmopressin is variable. On the other hand, desmopressin is ineffective in treating patients with type 3 VWD, who therefore necessitate replacement therapy with purified human VWF associated with FVIII, at least on the first administration. The patients managed in hospitals that have centres specialized in haemostasis and thrombosis have a favourable prognosis, even in the presence of the most severe forms of the disease [55,56].  
Prolonged bleeding is frequently observed following tooth extractions or associated with professional oral hygiene procedures. Treatments should be carefully considered in relation to the patient's state of health and the severity of the disease, in coordination with the haematologist [55,57].  
In patients responsive to therapy, desmopressin is administered as a preventive measure for interventions at risk, while replacement therapy of the deficient factor is carried out to reduce postoperative bleeding in refractory patients [57,58].