Abstract Number: OC 08.3
Meeting: ISTH 2021 Congress
Background: Non-severe hemophilia A patients can peri-operatively be treated with desmopressin or factor VIII (FVIII) concentrate. Desmopressin increases FVIII levels. However, interpatient variability of FVIII response is high. If increase is insufficient, FVIII concentrate is necessary. The 2020 WFH guideline states that combination therapy can overcome downsides of DDAVP or FVIII concentrate monotherapy. However, combination therapy is not common practice and difficult to implement.
Aims: To assess feasibility, accuracy and FVIII concentrate savings of peri-operative pharmacokinetic (PK)-guided dosing of desmopressin combined with FVIII concentrate in non-severe hemophilia A.
Methods: Peri-operative hemophilia A patients responsive to desmopressin were included. Desmopressin was administered intravenously (0.3 µg/kg) once-a-day, maximally for three consecutive days. Based on previously determined desmopressin response, additional FVIII concentrate dosing was calculated using PK-guidance. Modeling technique was continuously adapted and improved based on study data. FVIII activity was determined before/after combination therapy (trough and peak). A predicted FVIII level by the desmopressin-FVIII-PK-model was considered accurate if difference between predicted and measured FVIII level was ≤0.2 IU/ml. Hypothetical FVIII concentrate loading dose was calculated, assuming an increase of 0.02 IU/ml per IU concentrate per kilogram. Local ethics committee approval was obtained and patients provided written informed consent.
Results: Twenty-one procedures were performed in 20 hemophilia patients, 19 mild and 1 moderate. Median age was 47 years (interquartile range (IQR) 40 – 59). FVIII concentrate loading dose per patient was 1250 IU (median; IQR 1000 – 1750) lower than hypothetical. Predictions were accurate in 13/21 (61.9%) pre-operative peak levels at day 0 (D0), 14/19 (73.7%) at day 1 (D1) and 13/17 (76.5%) at day 2 (D2) post-operative trough levels (Figures 1 and 2).
Conclusions: Peri-operative combination therapy of desmopressin and FVIII concentrate under PK-guidance in non-severe hemophilia A provides a feasible, accurate treatment for the majority of patients. This approach resulted in considerable FVIII concentrate savings.
To cite this abstract in AMA style:Romano LGR, Schütte LM, van Hest RM, Meijer K, Laros - van Gorkom BAP, Nieuwenhuizen L, Eikenboom J, Heubel-Moenen FCJI, Uitslager N, Coppens M, Fijnvandraat K, Driessens MHE, Polinder S, Cnossen MH, Leebeek FWG, Mathôt RAA, Kruip MJHA, On behalf of the SYMPHONY Consortium . Peri-operative PK-guided Dosing of Desmopressin Combined with FVIII Concentrates in Hemophilia A: Final Results of the DAVID Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/peri-operative-pk-guided-dosing-of-desmopressin-combined-with-fviii-concentrates-in-hemophilia-a-final-results-of-the-david-study/. Accessed September 22, 2023.
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