Von Willebrand disease (VWD)

Overview

Von Willebrand disease (VWD) is the most common inherited bleeding disorder worldwide.

It is caused by a quantitative or qualitative deficiency of von Willebrand factor (vWF), a protein essential for:

• Platelet adhesion to subendothelial collagen.

• Platelet aggregation.

• Stabilization and protection of factor VIII.

VWD primarily causes mucocutaneous bleeding. Severe forms may present with joint and deep tissue bleeding similar to haemophilia.

It affects both sexes, but women are more commonly diagnosed due to menstrual and obstetric bleeding.

Classification

VWD is classified into three major types:

Type 1

• Partial quantitative deficiency of vWF.

• Most common type.

• Usually mild.

Type 2

• Qualitative defect of vWF.

• Includes:

  • Type 2A.

  • Type 2B.

  • Type 2M.

  • Type 2N.

Type 3

• Severe quantitative deficiency of vWF.

• Rare and severe form.

Risk factors

• Positive family history.

• Female sex due to symptomatic menstrual and childbirth-related bleeding.

• Blood group O (associated with lower baseline vWF levels).

Clinical presentation

Common mucocutaneous bleeding features

• Easy bruising.

• Epistaxis.

• Gum bleeding.

• Menorrhagia.

• Prolonged bleeding after dental procedures.

• Prolonged bleeding after injury or surgery.

Severe disease features

Usually seen in severe VWD:

• Joint bleeding (haemarthrosis).

• Deep muscle haematomas.

• Post-surgical haemorrhage.

Bleeding tendency may worsen during:

• Trauma.

• Surgery.

• Childbirth.

Diagnostic criteria

Diagnosis requires:

• Clinical history of abnormal bleeding.

• Laboratory confirmation.

Investigations

Screening tests

• Full blood count.

• Platelet count is usually normal except in some severe cases such as type 2B.

• PT is usually normal.

• aPTT is usually normal but may be prolonged in severe cases due to reduced factor VIII.

• Bleeding time may be prolonged but can be normal in mild disease.

Confirmatory tests

• vWF antigen (vWF:Ag) assay.

• vWF activity assay (ristocetin cofactor assay).

• Factor VIII level.

• vWF multimer analysis for classification/subtyping.

Additional tests:

• Ristocetin-induced platelet aggregation test.

• Mixing studies if inhibitor is suspected.

• Bethesda assay if factor inhibitor is detected.

Management of Von Willebrand disease (VWD)

Treatment depends on:

• Type of VWD.

• Severity of bleeding.

• Clinical situation.

Non-pharmacological management

• Avoid aspirin and NSAIDs.

• Avoid intramuscular injections.

• Provide preoperative haematology consultation.

• Provide genetic counselling.

• Educate patients regarding bleeding precautions.

• Plan procedures with appropriate bleeding control measures.

Pharmacological treatment

Antifibrinolytic therapy

Used for mild bleeding.

• Etamsylate PO 500 mg 8 hourly until bleeding stops.

OR

• Tranexamic acid PO 500 mg 8 hourly until bleeding stops.

Note:

• Never give etamsylate or tranexamic acid to patients bleeding per urethra due to risk of clot retention in the urinary tract.

Desmopressin (DDAVP)

If there is no response to antifibrinolytic therapy:

• Desmopressin IV 0.3 µg/kg stat.

• Maximum dose: 20 µg.

Mechanism:

• Stimulates endothelial release of stored vWF and factor VIII.

Effective mainly in:

• Type 1 VWD.

• Some type 2 variants.

Not effective in:

• Type 3 VWD.

Monitor for:

• Hyponatraemia.

• Fluid retention.

vWF-containing factor VIII concentrate

Patients unresponsive to DDAVP may be treated with:

• Virus-inactivated vWF-containing factor VIII concentrate.

Indications include:

• Severe bleeding.

• Major surgery.

• Type 3 VWD.

• Failure of response to DDAVP.

Management of inhibitors

If there is no response to replacement therapy:

• Perform aPTT mixing study.

• Confirm inhibitor using Bethesda assay (BU).

• Manage with specialist haematology input.

Special situations

Menorrhagia

Management options include:

• Tranexamic acid.

• Hormonal therapy.

• DDAVP during menstruation when appropriate.

Pregnancy

Considerations:

• vWF levels usually rise during pregnancy.

• Risk of postpartum haemorrhage remains.

• Monitor vWF and factor VIII levels, especially in the third trimester.

Surgery

Management includes:

• Preoperative DDAVP trial where appropriate.

• Factor replacement for major procedures.

• Haematology consultation before surgery.

Complications

• Chronic iron deficiency anaemia.

• Severe haemorrhage.

• Postpartum haemorrhage.

• Inhibitor formation (rare).

Prevention

• Family screening.

• Avoid antiplatelet drugs.

• Pre-surgical planning.

• Regular haematology follow-up.