What are the risks of giving DDAVP (Desmopressin) to a patient with type 2B von Willebrand disease?

Risks of DDAVP in Type 2B von Willebrand Disease

DDAVP (desmopressin) is contraindicated in patients with type 2B von Willebrand disease due to the significant risk of inducing thrombocytopenia and potential thrombotic complications. 1

Mechanism of Risk in Type 2B VWD

• DDAVP causes the release of abnormal von Willebrand factor (VWF) with enhanced affinity for platelet glycoprotein Ib in patients with type 2B VWD 1
• This abnormal VWF has platelet-aggregating properties, leading to in vivo platelet aggregation 1
• The result is typically a variable degree of thrombocytopenia following DDAVP administration 2

Specific Risks and Concerns

• Thrombocytopenia: The most consistent adverse effect observed in type 2B VWD patients receiving DDAVP

  • Occurs in approximately 70% of type 2B patients, with some experiencing severe thrombocytopenia 2
  • Thrombocytopenia is particularly common in patients who already lack large VWF multimers 3

• Potential for thrombotic events:

  • The formation of platelet aggregates in circulation raises concerns about possible thrombotic complications 1
  • DDAVP can also cause hypertension in some patients, which could further increase thrombotic risk 4

• Reduced efficacy:

  • Type 2B VWD patients show significantly shorter VWF survival after DDAVP administration (half-life of ~4.5 hours vs normal 15.5 hours) 3
  • This reduced survival limits the hemostatic effectiveness of the treatment 3

Current Guidelines and Recommendations

• The FDA drug label for desmopressin specifically notes the increased risk of thrombosis in patients with Type 2B VWD due to platelet aggregation 4

• Clinical practice guidelines indicate that DDAVP:

  • Is effective primarily for type 1 VWD 5
  • Is ineffective in type 3 VWD and severe forms of type 1 and 2 VWD 5
  • Can induce transient thrombocytopenia in patients with type 2B VWD 5

• For type 2B VWD patients requiring hemostatic coverage:

  • Human-derived medium-purity FVIII concentrates complexed to Willebrand factor (such as Humate-P) are the preferred treatment option 6
  • These are indicated for patients with von Willebrand disease in whom desmopressin is known or suspected to be inadequate 6

Evolving Clinical Practice

Despite historical contraindication, some recent literature suggests:

• Some type 2B patients have been treated with DDAVP without significant adverse events, even when thrombocytopenia occurred 2
• A European survey found that DDAVP use in type 2B VWD remains controversial among specialists, with most centers preferring factor concentrates for these patients 7

Practical Approach

For patients with type 2B VWD requiring hemostatic coverage:

1. First-line therapy: Use VWF/FVIII concentrates rather than DDAVP 6, 5

2. If DDAVP is considered (which is generally not recommended):

   • Perform a test dose under controlled conditions to assess individual response 5
   • Monitor platelet count closely before and after administration 2
   • Have VWF/FVIII concentrates immediately available if needed 7
   • Be vigilant for signs of thrombotic complications 4

3. Contraindications to DDAVP (beyond type 2B VWD):

   • Moderate to severe renal impairment
   • Hyponatremia or history of hyponatremia
   • Heart failure or uncontrolled hypertension
   • Concomitant use with loop diuretics or systemic/inhaled glucocorticoids 4

In conclusion, while DDAVP is the treatment of choice for type 1 VWD, its use in type 2B VWD carries significant risks of thrombocytopenia and potential thrombotic complications, making VWF/FVIII concentrates the safer and recommended option for these patients.