How does pregnancy affect type 2B Von Willebrand disease (VWD)?

Pregnancy Effects on Type 2B Von Willebrand Disease

Pregnancy typically worsens type 2B von Willebrand disease (VWD), causing progressive thrombocytopenia and increased bleeding risk, requiring close monitoring and often prophylactic treatment during delivery and postpartum.

Pathophysiological Changes During Pregnancy

Type 2B VWD is characterized by a gain-of-function mutation that causes increased binding of von Willebrand factor (VWF) to platelets. During pregnancy, several important changes occur:

• Increased production of the abnormal VWF variant 1
• Progressive worsening of thrombocytopenia, especially in the third trimester 2, 3
• Paradoxical rise in VWF antigen levels but with dysfunctional activity 2
• Discrepancies between VWF antigen, ristocetin cofactor activity, and factor VIII levels 3

Clinical Manifestations

The clinical impact of pregnancy on type 2B VWD includes:

• Development or worsening of thrombocytopenia in 96% of pregnant women 4
• Severe thrombocytopenia (platelet count <100 × 10⁹/L) in 85% of cases, with mean platelet count of 33.7 × 10⁹/L 4
• High risk of postpartum hemorrhage (PPH):
  • Primary PPH occurs in approximately 45% of deliveries 4
  • Secondary PPH occurs in approximately 46% of deliveries 4

Monitoring Recommendations

Due to the rapid changes in hemostatic parameters during pregnancy, close monitoring is essential:

• Regular assessment of platelet count throughout pregnancy, with increased frequency in the third trimester 2
• Monitoring of VWF antigen, ristocetin cofactor activity, and factor VIII levels 2
• Assessment for bleeding symptoms, particularly as delivery approaches

Management During Pregnancy and Delivery

Pre-delivery Planning

• Multidisciplinary approach involving hematology, obstetrics, and anesthesiology 1
• Development of a specific delivery plan by 32-34 weeks gestation

Neuraxial Anesthesia Considerations

For neuraxial anesthesia in type 2B VWD patients, specific hemostatic parameters must be achieved:

• VWF activity level should be at least 50 IU/dL 5
• Platelet count should be at least 70 × 10⁹/L 5
• Additional consideration of bleeding history and other hemostatic parameters 5

Treatment Options for Delivery

1. VWF concentrate:

   • Recommended before delivery and in the postpartum period 6
   • Target VWF activity level of at least 50 IU/dL 5

2. Platelet transfusions:

   • May be required for severe thrombocytopenia 2, 6
   • Approximately 76% of deliveries require platelet transfusions 4

3. Antifibrinolytic therapy:

   • Tranexamic acid can be used as adjunctive therapy 6

4. Avoid desmopressin:

   • Contraindicated in type 2B VWD due to risk of worsening thrombocytopenia 7
   • FDA label specifically warns that desmopressin use in type 2B VWD may result in platelet aggregation, thrombocytopenia, and possibly thrombosis 7

Postpartum Management

• Continue monitoring for at least 2 weeks postpartum due to high risk of secondary PPH 4
• Maintain hemostatic therapy for at least 10-14 days after delivery
• Monitor for retained placental tissue, which can cause delayed bleeding 2

Key Pitfalls and Caveats

1. Misdiagnosis: Type 2B VWD should be considered in the differential diagnosis of thrombocytopenia developing during pregnancy, particularly when evidence for immune thrombocytopenia is lacking 3

2. Treatment risks: Inappropriate use of desmopressin can worsen thrombocytopenia and increase thrombosis risk 7

3. Monitoring challenges: The rapid changes in VWF parameters and platelet count require vigilant monitoring throughout pregnancy 2

4. Neonatal considerations: Infants may inherit type 2B VWD and require monitoring for bleeding complications 6

5. Underestimation of bleeding risk: Despite rising VWF levels during pregnancy, the bleeding risk remains high due to the dysfunctional nature of the VWF and associated thrombocytopenia 1