Von Willebrand Disease (VWD) is the most common inherited bleeding disorder worldwide, caused by quantitative or qualitative deficiency of von Willebrand factor (vWF). vWF is essential for:

• Platelet adhesion to subendothelial collagen

• Platelet aggregation

• Stabilization and protection of factor VIII

VWD primarily results in mucocutaneous bleeding. Severe forms may present with joint or deep tissue bleeding, resembling hemophilia.

VWD affects both sexes, but women are more likely to seek medical attention due to menorrhagia and obstetric bleeding.

Classification

VWD is classified into three major types:

• Type 1 – Partial quantitative deficiency (most common, mild)

• Type 2 – Qualitative defect (subtypes 2A, 2B, 2M, 2N)

• Type 3 – Severe quantitative deficiency (rare, severe)

Risk Factors

• Positive family history (autosomal dominant in most cases)

• Female sex (symptomatic due to menstruation/childbirth)

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

Clinical Presentation (Signs and Symptoms)

Mucocutaneous Bleeding (Most Common)

• Easy bruising

• Epistaxis

• Gingival bleeding

• Menorrhagia

• Prolonged bleeding after dental procedures

Severe Disease (Type 3)

• Hemarthrosis

• Deep muscle hematomas

• Post-surgical hemorrhage

Bleeding tendency may worsen during surgery, trauma, or childbirth.

Diagnostic Criteria

Diagnosis requires clinical history plus laboratory confirmation.

A. Clinical Criteria

• Personal history of abnormal bleeding

• Positive family history of bleeding disorder

B. Laboratory Findings

• Prolonged bleeding time (may be normal in mild cases)

• Platelet count: Normal (except in Type 2B severe cases)

• aPTT: May be prolonged (due to reduced factor VIII)

• PT: Normal

C. Confirmatory Tests

• vWF antigen (vWF:Ag) level

• vWF activity (ristocetin cofactor assay)

• Factor VIII level

• vWF multimer analysis (subtyping)

Investigations

• Complete blood count (CBC)

• Coagulation profile (PT, aPTT)

• vWF antigen assay

• vWF activity assay

• Factor VIII assay

• Ristocetin-induced platelet aggregation test

• Mixing studies (if inhibitor suspected)

• Bethesda assay (if factor inhibitor detected)

Management

Treatment depends on disease type, severity, and bleeding context.

A. Non-Pharmacological

• Avoid aspirin and NSAIDs

• Avoid intramuscular injections

• Preoperative hematology consultation

• Genetic counseling

• Education regarding bleeding precautions

B. Pharmacological

1. Antifibrinolytic Therapy (Mild Bleeding)

• Tranexamic acid 500 mg PO every 8 hours until bleeding stopsOR

• Etamsylate 500 mg PO every 8 hours

Contraindicated in patients with hematuria (risk of clot retention in urinary tract).

2. Desmopressin (DDAVP)

• 0.3 µg/kg IV infusion

• Maximum dose: 20 µg

• Dilute in normal saline and infuse over 20–30 minutes

Mechanism: Stimulates endothelial release of vWF and factor VIII.

Effective in:

• Type 1 VWD

• Some Type 2 variants

Not effective in:

• Type 3 VWD

Monitor for:

• Hyponatremia

• Fluid retention

3. vWF-Containing Factor VIII Concentrates

Indicated if:

• No response to DDAVP

• Major surgery

• Severe bleeding

• Type 3 VWD

Use virus-inactivated plasma-derived vWF/FVIII concentrate.

Management of Inhibitors

If no response to replacement therapy:

• Perform aPTT mixing study

• Confirm with Bethesda assay (BU)

• Manage with specialist hematology input

Special Situations

Menorrhagia

• Tranexamic acid

• Hormonal therapy (oral contraceptives)

• DDAVP during menses

Pregnancy

• vWF levels rise during pregnancy

• Risk of postpartum hemorrhage

• Monitor vWF and FVIII levels in third trimester

Surgery

• Preoperative DDAVP trial

• Factor replacement if major procedure

Complications

• Chronic iron deficiency anemia

• Severe hemorrhage

• Postpartum hemorrhage

• Inhibitor formation (rare)

Prevention

• Family screening

• Avoid antiplatelet drugs

• Pre-surgical planning

• Regular hematology follow-up