Von Willebrand Disease (VWD)

Background

Bleeding disorder resulting from deficiency or abnormal function of Von Willebrand Factor (VWF)
VWF is a multimeric glycoprotein which has two main functions:
- To assist in platelet plug formation by binding circulating platelets to the site of vessel damage
- To bind to coagulation factor VIII preventing its clearance from the plasma

VWD is subdivided into three types determined by the nature of the mutations in the VWF gene.

Type 1 VWD:
- True Type 1 have levels of VWF antigen and/or activity of <0.3 IU/ml (activity level is measured by the Ristocetin Cofactor Activity (RCo) or collagen binding (CBA) assays). FVIII may also be low
Type 2 VWD:
- Subdivided into types 2A, 2B, 2M, 2N
- Type 2 VWD is characterised by abnormal function of the VWF protein and the RCo or CBA assays are lower than the VWF antigen in types 2A, 2B and 2M
- In Type 2N VWD, the functional abnormality involves the binding of VWF to FVIII and the FVIII is low but the VWF levels may not be low
Type 3 VWD:
- Type 3 have very low levels of VWF and FVIII and have the most severe bleeding phenotype which is akin to severe Haemophilia

Other subcategories include those with Low VWD and Platelet-type VWD.

Severity and presentation of VWF level and activity
	VWF antigen and /or activity	Clinical bleeding phenotype
Low VWF	0.3-0.5 IU/ml	Some patients may bleed with invasive procedures, or have menorrhagia or mucocutaneous bleeding
Type 1	<0.3 IU/ml	Bleeding after invasive dental or surgical procedures, menorrhagia, mucocutaneous bleeding
Type 2	<0.3 IU/ml (RCo or CBA) Ratio of activity to antigen <0.5-0.7	Variable bleeding tendency
Type 3	Variable bleeding tendency	Mucocutaneous bleeding, menorrhagia, post- operative bleeding. May have haemarthrosis, muscle haematomas

Prescribers must ensure that they prescribe the correct clotting factor concentrate e.g. Wilate or Veyvondi for VWD
Not all patients VWD or with low VWF require clotting factor concentrate and the use of alternative treatments may be indicated e.g. DDAVP and/or TXA
The patient's treatment of choice must be confirmed with the relevant CCC
Minor bleeding involving mucosal surfaces of the nose, mouth or female genital tract can be treated with TXA alone
Excessive menstrual bleeding can be treated with the addition of hormonal therapy e.g. the combined oral contraceptive pill or progesterone only pill or consideration can be given to progesterone releasing intra-uterine system (Mirena)
For more extensive or major bleeding, DDAVP or VWF concentrate should be used. The choice of agent will depend on the age of the patient, the presence of or risk factors for arteriovascular disease and the documented response of the patient to DDAVP
The CCC will advise on the appropriate treatment to use
The Clinician should establish the treatment of choice i.e. Wilate, DDAVP®/Desmopressin Injection and/or Tranexamic Acid