What are the treatment recommendations for a pregnant woman with type 2B von Willebrand disease on Desmopressin (DDAVP)?

Management of Pregnant Women with Type 2B von Willebrand Disease on Desmopressin (DDAVP)

For pregnant women with Type 2B von Willebrand disease, desmopressin (DDAVP) should generally be avoided and replaced with von Willebrand factor (VWF) concentrates as the primary treatment due to the risk of worsening thrombocytopenia and potential bleeding complications.

Understanding Type 2B VWD in Pregnancy

Type 2B von Willebrand disease (VWD) is a rare qualitative defect in VWF characterized by:

• Enhanced binding of VWF to platelet GPIbα receptors
• Preferential loss of high molecular weight VWF multimers
• Potential thrombocytopenia, especially during pregnancy
• Increased risk of bleeding complications

Key Pregnancy Considerations

• Pregnancy naturally increases VWF levels in most women with VWD
• In Type 2B VWD, this increase in dysfunctional VWF can worsen thrombocytopenia 1
• Platelet counts may decline significantly in the third trimester, with sharp decreases in the week before delivery 2
• Postpartum hemorrhage occurs in approximately 60% of deliveries despite prophylactic treatment 2

Treatment Recommendations

Antepartum Management

1. Avoid desmopressin (DDAVP)

   • DDAVP may cause transient decreases in platelet count in Type 2B VWD patients 3
   • This can lead to increased bleeding risk, especially problematic during pregnancy

2. Use VWF concentrates as primary treatment

   • VWF-FVIII plasma concentrates are the mainstay of therapy 4, 3
   • Target VWF activity levels ≥50 IU/dL for routine management 5
   • For invasive procedures, target higher levels as needed

3. Monitor laboratory parameters frequently

   • Track VWF:Ag, VWF activity, FVIII levels, and platelet count throughout pregnancy
   • Expect rapid coagulation changes requiring continual monitoring 4
   • Pay special attention to third trimester when thrombocytopenia may worsen

Labor and Delivery Management

1. Pre-delivery preparation

   • Administer VWF concentrates to achieve target levels before delivery
   • Consider platelet transfusions if severe thrombocytopenia develops (though results may be suboptimal) 3
   • Discontinue LMWH (if used for thromboprophylaxis) at least 24 hours prior to induction or cesarean section 5

2. Neuraxial anesthesia considerations

   • Ensure VWF activity level ≥50 IU/dL before neuraxial anesthesia 5
   • Monitor platelet count - neuraxial anesthesia generally requires platelets ≥70 × 10⁹/L 5
   • Type 2B VWD requires special consideration due to potential thrombocytopenia

3. Mode of delivery

   • Decision should be based on obstetric indications rather than VWD status alone
   • Avoid traumatic delivery methods when possible

Postpartum Management

1. Extended prophylaxis

   • Continue VWF concentrates for at least 2 weeks postpartum 6
   • Monitor for delayed postpartum hemorrhage, which may occur despite adequate prophylaxis
   • Target VWF activity levels ≥50 IU/dL during this period

2. Frequent monitoring

   • Continue laboratory monitoring in the postpartum period
   • Be vigilant for signs of bleeding, particularly in the first 2 weeks

Special Considerations by Genetic Variant

• Patients with p.Arg1306Trp mutation may experience more severe thrombocytopenia (75% of cases) 2
• Patients with p.Arg1308Cys mutation have lower rates of thrombocytopenia (58.3%) 2
• Management may need to be tailored based on specific genetic variant

Potential Complications

• Postpartum hemorrhage (occurs in approximately 60% of deliveries) 2
• Progressive thrombocytopenia during pregnancy, especially in third trimester
• Retained placenta requiring additional management 4
• Suboptimal response to platelet transfusions if needed 3

By following these recommendations and maintaining close monitoring throughout pregnancy and the postpartum period, the risk of bleeding complications in pregnant women with Type 2B VWD can be minimized while ensuring optimal maternal and fetal outcomes.