Search for a rare disease
Other search option(s)
Von Willebrand disease type 2
Type 2 von Willebrand disease (type 2 VWD) is a form of VWD (see this term) characterized by a bleeding disorder associated with a qualitative deficiency and functional anomalies of the Willebrand factor (von Willebrand factor; VWF).
ORPHA:166081Classification level: Subtype of disorder
- Synonym(s): -
- Prevalence: 1-5 / 10 000
- Inheritance: Autosomal dominant or Autosomal recessive
- Age of onset: All ages
- ICD-10: D68.0
- OMIM: 613554
- UMLS: C1264040
- MeSH: D056728
- GARD: -
- MedDRA: -
The type 2 disease accounts for between 20 and 45% of cases of VWD.
Age of onset of the bleeding anomalies varies, with earlier onset being associated with more severe VWF deficiency. Four type 2 VWD subtypes have been described (types 2A, 2B, 2M and 2N; see these terms). Three of these subtypes are associated with anomalies in the interaction of VWF with platelets and/or the subendothelium, and are caused by VWF multimerization anomalies (type 2A), increased VWF affinity for platelets (type 2B), or decreased VWF affinity for platelets (type 2M). The fourth subtype (type 2N) is associated with decreased VWF affinity for factor VIII (FVIII). Types 2A, 2B and 2M are characterized by mucocutaneous manifestations (menorrhagia, epistaxis, gastrointestinal hemorrhage etc.). For the type 2N disease, in which the interactions between the platelets and the vessel walls are often normal and the FVIII deficiency is usually only moderate, spontaneous abnormal bleeding events are less frequent than in the other forms. However, there is an increased risk of abnormal bleeding following an invasive procedure associated with all type 2 subtypes.
The VWF gene (12p13.3) anomalies that lead to type 2 VWD involve the well-defined functional domains of the VWF protein.
For subtypes 2A, 2B and 2M, diagnosis is suspected following detection of a notably more profound decrease in functional VWF levels than in VWF antigen levels. This discrepancy between the functional VWF levels and VWF antigen levels also allows the type 2 disease to be distinguished from the other forms of VWD (types 1 and 3 VWD; see these terms). However, more specific laboratory tests (analysis of the structure and distribution of the multimers) are required to diagnose the exact type 2 subtype. Diagnosis of type 2N is suspected when the decrease in FVIII levels is markedly more profound than that of VWF.
Subtypes 2A, 2B and 2M can be differentiated from acquired von Willebrand syndrome (AVWS; see this term), clinically by the onset of bleeding manifestations at a young age, a family history of the disease and the absence of an underlying pathology, and through molecular analysis revealing a mutation in the VWF gene. Diagnosis of subtype 2N can only be confirmed through a factor VIII binding assay. This binding assay, together with molecular analysis of the VWF gene, allows type 2N VWD to be distinguished from hemophilia A (see this term).
Transmission of most type 2 subtypes is autosomal dominant, however, some 2A variants and the type 2N subtype are transmitted in an autosomal recessive manner. Genetic counseling should provide extensive information to patients and lead to evaluation of the family.
Management and treatment
Medication (such as tranexamic acid for ENT bleeding anomalies and estrogen-progesterone therapy for menorrhagia) provides an effective treatment and may be prescribed alone or as an adjuvant therapy. The response to desmopressin varies depending on the type 2 subtype, as the endogenous VWF released from the endothelial cells in response to this treatment displays the same functional anomalies as plasmatic VWF. Desmopressin is contraindicated in patients with subtype 2B. Preventative or curative treatment for abnormal bleeding events often involves substitution therapy with purified human VWF.
For patients managed within specialized hemostasis and thrombosis hospital centers, the prognosis is favorable, even for those with the most severe forms of the disease.
Article for general public