PB0645 - Population pharmacokinetics and Global hemostasis assays-based management in a critically-ill hemophilia patient without inhibitors on emicizumab after polytrauma.

Background: Patients with hemophilia (PWH) A without inhibitors on mimetic-antibody prophylaxis have a high-risk of major bleeding in the context of trauma. Anaphylaxis associated with replacement therapy in patients with hemophilia A has been reported as extremely rare, and recently transitioned to emicizumab. Factor VIII replacement remained as the standard therapy for breakthrough bleeding in PWH-on-emicizumab prophylaxis, and bovine chromogenic assays are required for its level monitoring. In addition, there is no consensus about the utility of global hemostasis assays and population pharmacokinetics (popPK) in the real-life practice of PWH-on-emicizumab.

Aims: Report the case of a critically-ill hemophilia A patient without inhibitors on emicizumab, with a history of anaphylaxis to recombinant standard half-life factor-VIII, and the hemostasis management after polytrauma using thromboelastography(TEG) and historical popPK.

Methods: Clinical and popPK data of the patient were obtained from the clinical registries and the WAPPs-Hemo platform, respectively. Thromboelastograms were performed at medical discretion while health care was provided (Table 1). Bovine chromogenic assays were performed in a central laboratory with no real-time availability.

Results: A polytraumatized 16-year-old male was transferred to our center complaining of upper abdominal pain. Magnetic resonance imaging showed a grade-II hepatic laceration, subcapsular hematoma, and secondary hemoperitoneum. Nonoperative management was elected, with recombinant-site-specific pegylated factor VIII (damoctocog-alfa-pegol) administered based on popPK and adjusted in accordance with TEG findings (Graphic 1). A resolution was achieved after 10-days of this tailored scheme. Angioembolization was not necessary. No adverse events were reported. The anaphylaxis history was studied before the polytrauma event, and it identified damoctocog-alfa-pegol as a safe therapy.

Conclusion(s): This is an exceptional case of a polytraumatized PWH-on-emicizumab without inhibitors and a history of anaphylaxis, managed with EHL-Factor-VIII tailored by popPK and TEG. This suggests the inclusion of these tools in clinical settings without the availability of real-time bovine chromogenic assays.