Abstract Number: PB0556
Meeting: ISTH 2021 Congress
Background: Patients with non-severe hemophilia A can be treated peri-operatively with desmopressin or factor VIII (FVIII) concentrate. Desmopressin leads to increase of FVIII levels, however, interpatient variability is high. If insufficient, FVIII concentrate is used. Desmopressin combined with FVIII concentrate is not common practice, but can overcome downsides of monotherapy (2020 WFH guideline). Furthermore, desmopressin is less expensive than concentrate and combined treatment could save costs.
Aims: To compare efficacy and FVIII consumption of peri-operative pharmacokinetic (PK)-guided combination treatment (desmopressin and FVIII concentrate) versus PK-guided FVIII concentrate monotherapy in non-severe hemophilia A patients undergoing small procedures.
Methods: Non-severe hemophilia A patients responsive to desmopressin undergoing a minor intervention were included in this two-armed randomized clinical trial. In the standard treatment (control) arm only a PK-guided dose of FVIII concentrate was administered. In the intervention arm desmopressin was administered intravenously (0.3 µg/kg) with additionally, based on earlier reported desmopressin response, a PK-guided FVIII concentrate dose. FVIII trough and peak levels were determined in both arms. A predicted FVIII level was considered accurate if difference between measured and predicted FVIII level was ≤0.2 IU/ml. Local ethics committee approval was obtained and patients provided written informed consent.
Results: Patient and procedure characteristics are described in Table 1. All FVIII peak responses after desmopressin (peak desmopressin response) were predicted accurately. For peak of FVIII concentrate (intervention) 5/6 (83.3%) and peak of FVIII concentrate (control) 5/6 (83.3%) measurements were also accurate (Figure 2). Combination treatment resulted in ~47% lower FVIII concentrate consumption at loading dose (p = 0.009).
|Characteristic||Number (%) / median [interquartile range]|
|Control (FVIII) (n = 6)||Intervention (combination) (n = 6)|
|Age (years)||32 [26.3 – 49]||57 [51.8 – 62.5]|
|Lowest measured FVIII (IU/ml)||0.12 [0.10 – 0.13]||0.12 [0.09 – 0.17]|
|Study loading dose FVIII (IU)||3750 [3375 – 4000]||1750 [1250 – 2750]|
Oral and maxillofacial
|Bleeding complications||1 (16.7)||1 (16.7)|
Conclusions: Efficacy of peri-operative combination treatment of desmopressin and FVIII concentrate under PK-guidance was similar to PK-guided FVIII concentrate monotherapy in non-severe hemophilia A patients. Furthermore, significantly less FVIII concentrate was used with combination therapy. Therefore, combination therapy should be considered as treatment of choice for small procedures in non-severe hemophilia A.
To cite this abstract in AMA style:Romano LGR, Schütte LM, van Hest RM, Meijer K, Laros - van Gorkom BAP, Heubel-Moenen FCJI, Driessens MHE, Polinder S, Cnossen MH, Leebeek FWG, Mathôt RAA, Kruip MJHA, On behalf of the SYMPHONY Consortium . Randomized Clinical Trial of PK-guided Treatment of Desmopressin Combined with FVIII Concentrate versus Only FVIII Concentrate in Peri-operative Hemophilia A Patients: Final Results of the Little DAVID Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/randomized-clinical-trial-of-pk-guided-treatment-of-desmopressin-combined-with-fviii-concentrate-versus-only-fviii-concentrate-in-peri-operative-hemophilia-a-patients-final-results-of-the-little-davi/. Accessed September 24, 2021.
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