Case 33 – summary

Von Willebrands disease
The aim of this case was to identify a patient with Von Willebrands disease and arrange appropriate investigations.

Von Willebrand disease (vWD) is a common, inherited, genetically and clinically heterogeneous hemorrhagic disorder caused by a deficiency or dysfunction of the protein termed von Willebrand factor (vWF).

vWD is divided into three major categories:
1. partial quantitative deficiency (type I),
2. qualitative deficiency (type II), ). further divided into four variants (2A, 2B, 2N, 2M), based on characteristics of dysfunctional vWF
3. total deficiency (type III).

In order to determine whether further investigation is appropriate a bleeding history can be useful.

Bleeding History, suggested symptoms to question:
• Nose bleeding: 2 episodes without a history of trauma not stopped by short compression of 10 min or 1 episode requiring blood transfusion
• Prolonged bleeding from trivial wounds lasting 15 min or recurring spontaneously during the 7 d after wounding
• Cutaneous hemorrhage and bruisability with minimal or no apparent trauma as a presenting symptom or requiring medical treatment
• Oral cavity bleeding that requires medical attention, such as gingival bleeding or bleeding with tooth eruption or bites to lips and tongue
• Spontaneous gastrointestinal bleeding requiring medical attention or resulting in acute or chronic anemia unexplained by ulceration or portal hypertension
• Heavy, prolonged, or recurrent bleeding after tooth extraction or other oral surgery such as tonsillectomy and adenoidectomy requiring medical attention
• Menorrhagia resulting in acute or chronic anemia or requiring medical treatment not associated with structural lesions of the uterus
• Bleeding from other skin or mucous membrane surfaces requiring medical treatment (eg, eye, ear, respiratory tract, or genitourinary tract other than uterus)

Investigations:

VWD

• Initial haemostatic tests – FBC, PLt count, APTT, PT, Fibrinogen. If bleeding history is strong, consider performing initial VWB assays.
• If APTT corrects on mixing studies, or APTT is normal consider VWB assays
• Perfor VWF:Ag, VWF:RCo, FVIII:C
• If one or more are positive : consider repeat assays, check VWF Ag: RCo ratio, multimer distribution, collagen binding, RIPA or platelet binding, FVIII binding, platelet VWF studies, DNA sequencing for VWF gene.

Type 2B

• Characterized by gain-of-function mutations of the binding site for GP1bA, leading to rapid clearance of the platelet/VWF complex.
• Thrombocytopenia may occur
• Diagnosis is confirmed by two test:
o LD-RIPA is used to enhance platelet agglutination in the presence of gain-of-function mutations. Low dose of ristocetin does not cause binding and aggregation of platelets in sample from normal persons, but does cause VWF binding and aggregation of platelets in sample from patients with either type 2B VWD or patients with platelet type (pseudo) VWD (caused by a mutation in platelet GP1bA).
o VWF platelet-binding assay (VWF:PB) differentiates between type 2B and platelet type VWD. This assays measures the binding of VWF to normal paraformaldehyde-fixed platelets using low concentrations of ristocetin. Patients with type 2B exhibits increased platelet binding, whereas people whi have platelet-type VWD have normal VWF:PB with low doses of ristocetin.
• Treatment of these two conditions differs therefore it is important to differentiate between them. Type 2b is treated with VWF, and pseudo VWD requires platelet transfusion.

References:
Making a diagnosis of VWD. American Society of Haematology. Branchford B. R, Di Paolo. J. http://asheducationbook.hematologylibrary.org/content/2012/1/161.full.pdf
Evaluation and management of Von-willebrand disease. National heart, lung and blood institute. http://www.nhlbi.nih.gov/health-pro/guidelines/current/von-willebrand-guidelines/full-report/3-diagnosis-evaluation

About TeamHaem

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