Who should a patient with abnormal von Willebrand (VWD) disease be referred to?

Referral for Abnormal von Willebrand Disease

Patients with abnormal von Willebrand disease should be referred to a hematologist, preferably one with expertise in bleeding disorders or at a hemophilia treatment center. 1

Understanding von Willebrand Disease

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting approximately 1% of the general population. It results from deficiency or dysfunction of von Willebrand factor (VWF), a multimeric plasma glycoprotein that:

• Mediates platelet adhesion and aggregation at sites of vascular injury
• Carries and stabilizes blood coagulation factor VIII in circulation 2

Types of VWD

• Type 1: Partial quantitative deficiency (~75% of cases)
• Type 2: Qualitative deficiency with four subtypes (2A, 2B, 2M, 2N)
• Type 3: Virtually complete quantitative deficiency (rare, ~1 in 1,000)
• Acquired von Willebrand Syndrome (AVWS): Associated with various medical conditions 2

Diagnostic Process Before Referral

Primary care physicians should initiate the evaluation when VWD is suspected:

1. Clinical assessment:

   • Document frequency and severity of bleeding episodes
   • Look for easy bruising, nosebleeds, mucosal bleeding, gastrointestinal bleeding
   • In women, assess for heavy menstrual bleeding (affects 5-20% of women with menorrhagia) 1
   • Review family history for bleeding disorders 3

2. Initial laboratory tests:

   • Complete blood count (CBC)
   • Prothrombin time (PT)
   • Activated partial thromboplastin time (PTT) 3

3. Core VWD tests for patients with mucocutaneous bleeding history:

   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII) 3

When to Refer to a Hematologist

Referral to a hematologist is indicated when:

• Abnormal VWF test results are present
• Patient has significant bleeding symptoms
• There is a strong family history of VWD 3

Specialized Care by Hematologists

Hematologists with expertise in bleeding disorders provide:

1. Definitive diagnosis:

   • Specialized laboratory testing to determine VWD type and subtype
   • Calculation of VWF:RCo to VWF:Ag ratio (ratio <0.5-0.7 suggests Type 2 VWD)
   • Repeat testing (VWF levels can vary and may need to be tested up to 3 times) 3
   • Genetic testing for confirmation of type 2 subtypes and type 3 VWD 4

2. Treatment planning:

   • First-line treatment selection (desmopressin vs. factor concentrates)
   • Desmopressin for mild to moderate Type 1 VWD
   • VWF-containing factor concentrates for Type 2B, Type 3, and severe forms of Type 1 and 2 3, 5
   • Antifibrinolytic medications for minor procedures 1

3. Special considerations:

   • Management during pregnancy and childbirth
   • Surgical planning and perioperative care
   • Prophylaxis for patients with recurrent joint bleeding 6

Hemophilia Treatment Centers

For optimal care, referral to a hemophilia treatment center (HTC) is recommended, especially for:

• Complex cases
• Major surgeries
• Childbirth management
• Patients with severe disease 1

HTCs provide comprehensive care with experienced:

• Hematologists
• Anesthesiologists
• Pharmacists
• Laboratory support 1

Special Considerations for Women

Women with VWD require specialized care for:

• Heavy menstrual bleeding management
• Pregnancy planning
• Childbirth (risk of postpartum hemorrhage)
• Interdisciplinary management with gynecologists/obstetricians 7

Pitfalls to Avoid

• Delayed diagnosis: VWD is often underdiagnosed, particularly in women with menorrhagia
• Inadequate testing: Single VWF tests may be insufficient due to variability in levels
• Inappropriate treatment: Using desmopressin in Type 2B VWD can cause thrombosis 5
• Failure to monitor sodium levels: Desmopressin can cause hyponatremia 5
• Inadequate perioperative planning: Major surgeries require specialized management

Remember that von Willebrand disease is a lifelong condition requiring ongoing specialized care. Early referral to a hematologist with expertise in bleeding disorders ensures proper diagnosis, treatment, and management of this complex condition.