Peri‐operative desmopressin combined with pharmacokinetic‐guided factor VIII concentrate in non‐severe haemophilia A patients

Abstract

IntroductionNon‐severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility and safety has never been investigated.AimWe assessed the feasibility and safety of combination treatment in nonsevere haemophilia A patients.MethodsNon‐severe, desmopressin responsive, haemophilia A patients were included in one of two studies investigating peri‐operative combination treatment. In the single‐arm DAVID study intravenous desmopressin (0.3 μg/kg) once‐a‐day was, after sampling, immediately followed by PK‐guided FVIII concentrate, for maximally three consecutive days. The Little DAVID study was a randomized trial in patients undergoing a minor medical procedure, whom received either PK‐guided combination treatment (intervention arm) or PK‐guided FVIII concentrate only (standard arm) up to 2 days. Dose predictions were considered accurate if the absolute difference between predicted and measured FVIII:C was ≤0.2 IU/mL.ResultsIn total 32 patients (33 procedures) were included. In the DAVID study (n = 21), of the FVIII:C trough levels 73.7% (14/19) were predicted accurately on day 1 (D1), 76.5% (13/17) on D2. On D0, 61.9% (13/21) of peak FVIII:C levels predictions were accurate. In the Little DAVID study (n = 12), on D0 83.3% (5/6) FVIII:C peak levels for both study arms were predicted accurately. Combination treatment reduced preoperative FVIII concentrate use by 47% versus FVIII monotherapy. Desmopressin side effects were mild and transient. Two bleeds occurred, both despite FVIII:C > 1.00 IU/mL.ConclusionPeri‐operative combination treatment with desmopressin and PK‐guided FVIII concentrate dosing in nonsevere haemophilia A is feasible, safe and reduces FVIII consumption.