Репозиторий Университета

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2019 Wiley Periodicals, Inc. Background: Emicizumab is a bispecific antibody that bridges factor IXa and factor X to restore hemostasis in patients with hemophilia A (HA). Its efficacy and safety have been proven in multicenter trials. However, real world data regarding its use in very young children are currently lacking. Ancillary test results for monitoring emicizumab's hemostatic effect and their clinical correlations are scarce. Methods: Children with HA and inhibitors treated by emicizumab were prospectively followed at our center. Laboratory follow-up included rotational thromboelastometry (ROTEM) and thrombin generation (TG), prior to and during treatment. Results: Eleven children whose median age was 26 months were treated by emicizumab and followed for a median of 36 weeks. During follow-up, none experienced hemarthrosis or any other spontaneous bleeds. For 7/11 patients, emicizumab prophylaxis was sufficient to maintain hemostasis without additional supplemental therapy. Only 4/11 patients were occasionally treated with recombinant activated FVII for trauma. Two minor surgeries were safely performed without supplemental therapy while another procedure was complicated by major bleeding. TG parameters improved for all patients, correlating with their clinical status. Interestingly, the lowest TG values were obtained for patients experiencing bleeding episodes, while ROTEM parameters in all patients were close to the normal range. Conclusions: This study confirms the safety and efficacy of emicizumab in reducing bleeds in young children with HA with inhibitors, including infants. However, surgeries warrant caution as emicizumab prophylaxis may not be sufficient for some procedures. TG may more accurately reflect the hemostasis state than ROTEM in pediatric patients treated with emicizumab.

© Bionika Media Ltd. Aim. To estimate the effectiveness of the thrombin generation assay (TGA) in identifying high thrombogenic risk in pregnant women. Material and methods. The study comprised 30 healthy non-pregnant women (control group) and 32 women in the third trimester of pregnancy. Of the latter group, 22 women with complicated pregnancy comprised the study group while the remaining ten women made up the comparison group. After delivery, the patients in the study group were divided into subgroups with a favorable (n = 15) and adverse (n = 7) pregnancy outcomes. The state of the hemostatic system was examined using standard coagulation tests and TGA. Results. Thrombin generation assessed as endogenous thrombin potential (ETP), was statistically significantly higher in pregnant than in non-pregnant women (2300 ± 400 vs. 1700 ± 400, respectively, p <0.005). The patients with adverse pregnancy outcomes had statistically significantly higher ETP compared with women with favorable outcomes (2700 ± 600 vs. 2300 ± 300, respectively, p <0.005). Conclusion. TGA can be used to predict adverse pregnancy outcomes. Elevated ETP is associated with adverse pregnancy outcomes.