Isn't desmopressin (DDAVP) contraindicated in type 2B von Willebrand disease?

Desmopressin is Contraindicated in Type 2B von Willebrand Disease

Desmopressin is contraindicated in type 2B von Willebrand disease due to the risk of worsening thrombocytopenia. 1, 2

Mechanism of Contraindication

Type 2B von Willebrand disease is characterized by an abnormal von Willebrand factor (VWF) with enhanced affinity for platelet glycoprotein Ib receptors. This leads to several important consequences when desmopressin is administered:

• Desmopressin causes release of large and hyper-adhesive VWF multimers
• In type 2B patients, these released multimers have abnormally high binding affinity to platelets
• This results in spontaneous platelet aggregation and consumption
• The outcome is often profound thrombocytopenia (up to 90% drop in platelet count) 2

Evidence Supporting Contraindication

The FDA drug label specifically lists an "Increased Risk of Thrombosis in Patients with von Willebrand's Disease Type IIB" as a warning and precaution for desmopressin use 1. This is supported by clinical research showing:

• Desmopressin administration in type 2B patients can cause circulating platelet aggregates 2, 3
• The thrombocytopenia is directly linked to the release of abnormal VWF multimers from endogenous stores 3
• A randomized pilot trial demonstrated that desmopressin induced a profound (-90%) drop in platelet counts in a type 2B patient 2

Management Alternatives for Type 2B Patients

Since desmopressin is contraindicated, alternative management strategies for type 2B von Willebrand disease include:

1. VWF-containing concentrates (plasma-derived or recombinant) 4, 5
2. Cryoprecipitate (though virus-inactivated concentrates are preferred) 5
3. Antifibrinolytic agents as adjunctive therapy

Exceptions and Controversies

While desmopressin is generally contraindicated in type 2B disease, there are some conflicting reports:

• Some older studies suggest that selected type 2B patients might safely receive desmopressin in certain clinical situations 6, 3
• A 1996 study reported three type 2B patients who did not develop thrombocytopenia after desmopressin administration 6
• However, these are isolated reports and the consensus remains that desmopressin should be avoided in type 2B disease

Clinical Approach

When managing a patient with von Willebrand disease:

1. Accurately determine the subtype (type 1, 2A, 2B, 2M, 2N, or 3)
2. For type 2B specifically, avoid desmopressin and use VWF concentrates instead
3. For type 1 and some type 2 variants (not 2B), desmopressin may be appropriate at 0.3 μg/kg 4
4. Consider a test dose of desmopressin at diagnosis for non-2B patients to establish individual response patterns 7

Conclusion

The evidence strongly supports avoiding desmopressin in type 2B von Willebrand disease due to the risk of worsening thrombocytopenia. VWF-containing concentrates remain the treatment of choice for these patients.