What is the risk of a pregnant woman having a serious bleed during pregnancy if she has undiagnosed type 2B von Willebrand disease?

Risk of Serious Bleeding in Pregnant Women with Undiagnosed Type 2B von Willebrand Disease

Pregnant women with undiagnosed type 2B von Willebrand disease have a significant risk of serious bleeding during pregnancy, with reported cases showing progressive thrombocytopenia and increased bleeding risk, particularly during delivery and the postpartum period.

Understanding Type 2B von Willebrand Disease in Pregnancy

Type 2B von Willebrand disease (VWD) is characterized by a qualitative defect in von Willebrand factor (VWF) that causes a gain-of-function mutation, resulting in:

• Increased binding of VWF to platelets
• Progressive thrombocytopenia, especially during pregnancy
• Reduction in large VWF multimers
• Impaired platelet-dependent VWF activity

Physiological Changes and Risk Factors

During pregnancy, women with type 2B VWD experience unique challenges:

• VWF:Ag levels typically rise throughout pregnancy 1, 2
• This rise in dysfunctional VWF can paradoxically worsen thrombocytopenia 1
• Specific mutations (e.g., R1306W) are associated with more severe thrombocytopenia during pregnancy 3

Quantifying Bleeding Risk

The risk of serious bleeding in undiagnosed type 2B VWD during pregnancy is substantial:

• Case series have documented significant bleeding events requiring intervention 1, 3
• Postpartum hemorrhage is a major concern, with increased risk compared to the general population 4
• Retained placenta with associated bleeding has been reported 1
• Neonatal bleeding complications may occur if the child inherits the condition 3

Critical Periods of Bleeding Risk

1. First Trimester:

   • Risk of spontaneous abortion, though evidence is mixed on whether this is increased 4
   • Invasive procedures like amniocentesis carry heightened bleeding risk 5

2. During Delivery:

   • Significant risk of peripartum hemorrhage requiring hemostatic support 2
   • Need for platelet transfusions in cases with severe thrombocytopenia 1

3. Postpartum Period:

   • Delayed postpartum bleeding is common without continued hemostatic support 5
   • Risk of readmission for bleeding complications 1

Management Implications

For pregnant women with suspected or confirmed type 2B VWD:

• Regular monitoring of VWF parameters and platelet count throughout pregnancy is essential 1

• Preparation for delivery should include availability of:

  • VWF-FVIII concentrates
  • Platelet transfusions
  • Tranexamic acid

• Neuraxial anesthesia decisions remain controversial, with diverse physician practices 2

• Fetal delivery restrictions may be necessary to prevent neonatal bleeding 6

Key Considerations for Clinicians

• The diagnosis is often missed due to variable presentation and lack of prior bleeding history
• Laboratory parameters can change rapidly during pregnancy, requiring frequent monitoring
• The risk is mutation-specific, with some variants (e.g., R1306W) associated with more severe thrombocytopenia and bleeding risk 1
• Both maternal and fetal outcomes are at risk, especially if the child inherits the condition

Common Pitfalls in Management

1. Failure to recognize progressive thrombocytopenia as a sign of worsening disease rather than gestational thrombocytopenia
2. Inadequate preparation for delivery without appropriate blood products available
3. Premature discontinuation of hemostatic support after delivery, missing delayed bleeding complications
4. Overlooking the potential for neonatal bleeding complications if the child inherits the condition
5. Using desmopressin (DDAVP), which is relatively contraindicated in type 2B VWD as it may worsen thrombocytopenia 4

The management of pregnant women with type 2B VWD requires specialized care and close monitoring throughout pregnancy, with particular attention to the peripartum and postpartum periods to mitigate the substantial risk of serious bleeding complications.