Clinical Efficacy and Determinants of Response to Treatment with Desmopressin in Mild Hemophilia A

Abstract

Although desmopressin (DDAVP) is considered as the treatment of choice for many patients with mild hemophilia A, several aspects of DDAVP therapy remain unclear, including the rate and type of response and the molecular determinants of its clinical efficacy. To investigate these issues, we retrospectively studied all patients with mild hemophilia A followed up at the Parma Hemophilia Center. A total of 75 patients were enrolled who underwent a DDAVP test, and out of whom, 76% (57/75) had a complete or partial response. Response to DDAVP was significantly correlated to the patients' age (median age of responders and nonresponders: 24 and 18 y, respectively; p = 0.04) and type of mutation (all the 10 patients with mutations in the promoter region were nonresponders). The median basal factor VIII (FVIII):C level was significantly lower in responders than in nonresponders (0.14 vs. 0.19 IU/mL, respectively; p = 0.01); this was mainly due to nonresponders with promoter region mutations who had higher basal FVIII:C levels. During the 12-year follow-up, 82 of 237 (35%) bleeding episodes occurring in 27 responder patients were treated with 246 DDAVP infusions with complete or partial efficacy in 92% (75/82). Overall, 142 events were managed with 253 prophylactic DDAVP infusions, which were hemostatically effective in 96% of cases. No severe adverse reactions to DDAVP administration were recorded during the study period. These results document the safety and efficacy of DDAVP as a treatment or prevention of bleeding in patients with mild hemophilia A, also in the context of home treatment, and encourage the more widespread use of this product.

Long‐term outcomes from prophylactic or episodic treatment of haemophilia A: A systematic review

“…Median study follow‐up ranged from 5 to 19 years . Only one study, published in 2013 by Di Perna and colleagues, investigated patients with mild disease and was therefore excluded from our description and discussion of results, as mild disease may be considered its own type of haemophilia manifestation …”

Desmopressin in haemophilia: The need for a standardised clinical response and individualised test regimen

“…Response definitions in literature were based on clinical FVIII:C cut‐off values (i.e. FVIII:C≥0.30 IU/mL for minor and ≥0.50 IU/mL for major bleeds or surgery); some additionally included FVIII:C‐fold increase over baseline . Clinical cut‐off values seem most relevant, as FVIII:C‐fold increase over baseline was not associated with peak response or response sustainability.…”

“…Variations in definitions consist of use of different clinically relevant cut‐off values of FVIII activity level (FVIII:C) that have been proposed amongst others by the World Federation of Haemophilia, e.g. ≥0.30 for minor and ≥0.50 IU/mL for major bleeding or surgery, whereas others also incorporate FVIII:C‐fold increase over baseline to evaluate biological efficacy . Consequently, comparison of desmopressin responses between studies is difficult and patients are classified differently depending on definition.…”

Desmopressin responsiveness at a capped dose of 15 μg in type 1 von Willebrand disease and mild hemophilia A

“…In hemophilia A, various reports quote an overall response rate of 76-86% with a complete response rate of 64-68% [19][20][21]. The above studies mainly used the traditional weight-based dose of 0.3 mg/kg.…”