Are bleeding disorders such as von Willebrand disease inherited?

Inheritance Patterns of Bleeding Disorders

Yes, von Willebrand disease (VWD) is primarily inherited in an autosomal dominant pattern, particularly Type 1 and most Type 2 variants, while Type 3 follows an autosomal recessive inheritance pattern. 1

Inheritance Patterns of Common Bleeding Disorders

Von Willebrand Disease

• Prevalence: Most common inherited bleeding disorder, affecting up to 1% of the general population 1
• Inheritance pattern:
  • Type 1 and most Type 2 variants: Autosomal dominant 1
  • Type 3: Autosomal recessive 1
• Clinical significance: VWD causes excessive mucocutaneous bleeding, including nosebleeds, easy bruising, gingival bleeding, bleeding from small wounds, and menorrhagia or postpartum bleeding in women 2

Hemophilia

• Hemophilia A (Factor VIII deficiency):

  • X-linked recessive disorder primarily affecting males
  • Prevalence: 1/5,000 males 3
  • Can result in intracranial hemorrhage (ICH) in 5-12% of cases 3

• Hemophilia B (Factor IX deficiency):

  • X-linked recessive disorder primarily affecting males
  • Prevalence: 1/20,000 males 3
  • Similar bleeding risk profile to Hemophilia A 3

Other Inherited Bleeding Disorders

• Factor XI deficiency:

  • Autosomal recessive inheritance
  • Higher prevalence in Ashkenazi Jewish populations 3
  • Rarely causes severe bleeding manifestations

• Factor XIII deficiency:

  • Autosomal recessive inheritance
  • Prevalence: 1/2 million 3
  • High risk of ICH (33%) 3

Clinical Implications of Inheritance Patterns

1. Family screening: When VWD is diagnosed, family members should be considered for testing due to the autosomal inheritance pattern 4

2. Prenatal considerations:

   • Prenatal diagnosis is typically only required for women known to be carriers of VWD type 3 4
   • No spontaneous bleedings usually occur at birth even in severe type 3 VWD 4

3. Pre-menarchal testing: Girls growing up in families with a history of VWD should be tested before menarche to prepare for menstrual bleeding management 5

Diagnostic Approach for Suspected Inherited Bleeding Disorders

1. Laboratory evaluation:

   • For VWD: VWF antigen (VWF:Ag), VWF activity (VWF:RCo), and factor VIII levels 1
   • Complete blood count and coagulation profile (PT, aPTT) 1
   • Note that PT is typically normal in VWD, while aPTT may be prolonged in severe cases 1

2. Genetic testing:

   • Molecular screening can confirm phenotypic diagnosis and track VWF defects within families 4
   • Next-generation sequencing provides comprehensive VWF sequence information for patients with suspected VWD 6

Important Clinical Considerations

• When evaluating a patient with bleeding symptoms and a family history of bleeding disorders, always consider inherited conditions like VWD 7

• The diagnosis of VWD in children with bruising must be carefully distinguished from child abuse, as both can coexist 3

• Young children with VWD type 3 might carry deletions of the VWF gene that predispose to alloantibodies to VWF, requiring intensive investigation before starting extensive therapy with exogenous VWF concentrates 4

• Autosomal inheritance patterns mean that both males and females can be affected, unlike X-linked disorders like hemophilia that predominantly affect males 1