PMID-29491128 – Desmopressin in Hemophilia A Golden Jubilee Review
Mannucci PM. Use of desmopressin in the treatment of hemophilia A: towards a golden jubilee. Haemophilia. 2018;24(3):340-343.
Quick Reference
| Property | Value |
|---|---|
| PMID | 29491128 |
| DOI | 10.1111/hae.13438 |
| Year | 2018 |
| Journal | Haemophilia |
| Study Type | Narrative Review |
| Evidence Level | V |
| Sample | N/A (comprehensive expert review of clinical experience since 1977) |
| Peptide(s) Studied | Desmopressin |
Key Findings
- Desmopressin (DDAVP) was first used for hemophilia A in 1977, establishing nearly 50 years of clinical experience
- Mechanism: activates endothelial V2 receptors, triggering cAMP-mediated exocytosis of von Willebrand factor (vWF) and Factor VIII from Weibel-Palade bodies and other storage sites
- Raises Factor VIII levels 2-6 fold within 30-60 minutes of administration
- Effective for mild hemophilia A (baseline Factor VIII >5%) and most Type 1 von Willebrand disease
- Remains the treatment of choice for mild hemophilia A because it avoids the infection risk and inhibitor development risk of plasma-derived products
- Tachyphylaxis (reduced response) occurs with repeated doses within 24-48 hours due to depletion of endothelial stores
- Routes: IV (0.3 mcg/kg), SubQ (0.3 mcg/kg), high-concentration intranasal spray (150-300 mcg)
Study Design
Narrative expert review by Pier Mannucci (who pioneered the use of DDAVP in hemophilia), covering the history, mechanism, clinical applications, safety profile, and future directions of desmopressin in hemophilia A treatment over approximately 40 years of clinical use.
Limitations
- Narrative review by the originator of the clinical application — potential for confirmation bias
- Not a systematic review — study selection not standardized
- Limited quantitative synthesis of efficacy data
- Focus on hemophilia A with limited coverage of other bleeding disorders
Clinical Relevance
This review by the pioneer of desmopressin use in hemophilia provides authoritative context for understanding how a 9-amino-acid vasopressin analog can serve dual clinical roles: antidiuretic (V2-mediated renal water reabsorption) and hemostatic (V2-mediated endothelial release of coagulation factors). The distinction between V1 (vasopressor) and V2 (antidiuretic + hemostatic) receptor selectivity is fundamental to desmopressin's safety profile — by avoiding V1 activation, desmopressin achieves hemostatic effects without clinically significant blood pressure elevation. This principle of selective receptor targeting is broadly relevant to peptide therapy design. For the Ageless Peps Academy, desmopressin exemplifies how rational structural modifications of a natural peptide (vasopressin) can create a clinically superior therapeutic with enhanced selectivity and duration.
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#research #narrative-review #desmopressin #evidence-level-V