Tachyphylaxis and reproducibility of desmopressin response in peri-operative non-severe hemophilia A patients: implications for clinical practice

Background Desmopressin is frequently used peri-operatively in patients with non-severe hemophilia A. However, FVIII:C increase after desmopressin is interindividually highly variable. Tachyphylaxis has only been reported in test setting for hemophilia A patients, with a remaining response of approximately 70% after a second dose compared to a first dose. Objectives To study tachyphylaxis of FVIII:C response after multiple administration(s) of desmopressin in peri-operative non-severe hemophilia A patients.Patients/methods: We studied FVIII:C levels after desmopressin before (D0) and on day 1 (D1) and 2 (D2) after surgery in 26 patients of the DAVID and Little DAVID study. We studied tachyphylaxis by comparing the response at D1 and D2 with D0. We also assessed the reproducibility of the D0 response in comparison to an earlier performed desmopressin test. Results The median absolute FVIII:C increase was 0.50 IU/mL (0.35-0.74; n=23) at D0, 0.21 IU/mL (0.14-0.28; n=17) at D1 and 0.23 IU/mL (0.16-0.30; n=11) at D2. The median percentage of FVIII increase after the second administration (D1) compared to the first (D0) was 42.9% (29.2%-52.5%; n=17) and of the third (D2) compared to the first (D0) 36.4% (23.7%-46.9%; n=11). The FVIII:C desmopressin response at D0 was comparable to the desmopressin test response in 74% of the patients. Conclusions Tachyphylaxis in the surgical setting was considerably more pronounced than previously reported with FVIII:C at D1 and D2 of 36-43% of the initial response. Our results may have important implications for monitoring repeated desmopressin treatment, when used peri-operatively.