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

Abstract

Desmopressin (DDAVP) is commonly used in the treatment of patients with type 1 von Willebrand disease (VWD) and mild hemophilia A. A patient's responsiveness to DDAVP based on a 0.3 μg/kg dose determines future therapeutic efficacy of the drug. The aim of the study was to determine whether a capped dose of 15 μg subcutaneous DDAVP is able to achieve the same level of DDAVP responsiveness as previously reported. This is a retrospective chart review of patients from 1995 to 2013 in adults and children with type 1 VWD and hemophilia A weighing more than 50 kg. Levels of factor VIII, ristocetin cofactor, and von Willebrand factor antigen were measured before and after 1 h of administration of 15 μg of DDAVP. In patients with type 1 VWD, the complete response rate was 82.5% with a partial response rate of 12.5% and 5% nonresponders. In patients with mild hemophilia A, the complete response rate was 53.8% with a partial response rate of 38.5% and 7.7% nonresponders. These results using a capped 15-μg dose of DDAVP are similar to previously published reports using the 0.3-μg/kg dose.

How I treat type 2 variant forms of von Willebrand disease

“…51,52 Some national guidelines recommend a capped dose of 20 mg, 53 and recent retrospective data suggest that even a capped dose of 15 mg may be useful. 54 Desmopressin is however, contraindicated in type 2B because the transient appearance or aggravation of thrombocytopenia may lead to an increased risk of bleeding. In type 2N associated with homozygous or heterozygous R854Q mutation (by far the most frequent mutation), desmopressin is usually able to correct FVIII deficiency, although its half-life may be relatively short.…”

Desmopressin in non‐severe haemophilia A: Test‐response and clinical outcomes in a single Canadian centre review

“…Response to DDAVP may differ between patients with haemophilia of similar severity. Thus, before being used in the clinical setting, individual patient responsiveness to DDAVP should be assessed . Responsiveness is determined by measuring FVIII levels before, and at pre‐determined time points (eg 30, 60 minutes, etc.)…”

“…after administration of a test dose. What constitutes a response varies among investigators, and at least 10 different definitions of test‐response have been reported (Summarized in Table ) …”

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

“…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.…”

“…≥0.30 for minor and ≥0.50 IU/mL for major bleeding or surgery, [8][9][10] whereas others also incorporate FVIII:C-fold increase over baseline to evaluate biological efficacy. 1,[11][12][13][14][15] Consequently, comparison of desmopressin responses between studies is difficult and patients are classified differently depending on definition. Hence, establishment of a standardised uniform response is desirable.…”