The potential role of emicizumab prophylaxis in severe von Willebrand disease
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01.03.2021 |
Barg A.A.
Avishai E.
Budnik I.
Brutman T.B.
Tamarin I.
Dardik R.
Bashari D.
Misgav M.
Lubetsky A.
Lalezari S.
Livnat T.
Kenet G.
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Blood Cells, Molecules, and Diseases |
10.1016/j.bcmd.2020.102530 |
0 |
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© 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.
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The potential role of emicizumab prophylaxis in severe von Willebrand disease
|
01.03.2021 |
Barg A.A.
Avishai E.
Budnik I.
Brutman T.B.
Tamarin I.
Dardik R.
Bashari D.
Misgav M.
Lubetsky A.
Lalezari S.
Livnat T.
Kenet G.
|
Blood Cells, Molecules, and Diseases |
10.1016/j.bcmd.2020.102530 |
0 |
Ссылка
© 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.
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Emicizumab prophylaxis among infants and toddlers with severe hemophilia A and inhibitors—a single-center cohort
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01.11.2019 |
Barg A.
Avishai E.
Budnik I.
Levy-Mendelovich S.
Barazani T.
Kenet G.
Livnat T.
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Pediatric Blood and Cancer |
10.1002/pbc.27886 |
3 |
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© 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.
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The role of haemostasis in placenta-mediated complications
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01.09.2019 |
Gris J.
Bouvier S.
Cochery-Nouvellon É.
Mercier É.
Mousty È.
Pérez-Martin A.
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Thrombosis Research |
10.1016/S0049-3848(19)30359-7 |
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© 2019 Elsevier Ltd Normal pregnancy is associated with an increasing state of activation of the haemostatic system. This activation state is excessive in women with placenta-mediated pregnancy complications (PMPCs), including preeclampsia (PE). Platelet activation plays a crucial pathophysiological role in PE. The very early activation of coagulation in the intervillous space is mandatory for placental growth and morphogenesis but its excesses and/or inadequate control may participate to the emergence of the trophoblastic phenotype of PE. Extracellular vesicles, of endothelial but also of trophoblastic origin, can favour key cellular reactions of preeclampsia, acting as proactive cofactors. The understanding of this intricate relationship between haemostasis activation and PMPCs may provide interesting keys for new pathophysiological therapeutic developments.
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Evaluation of the rivaroxaban-influenced effect of ABCB1 and CYP3A5 gene polymorphisms on prothrombin time in patients after total hip or knee replacement surgery
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01.01.2018 |
Sychev D.
Minnigulov R.
Ryzhikova K.
Yudina I.
Lychagin A.
Morozova T.
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Bulletin of Russian State Medical University |
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0 |
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© 2018 Pirogov Russian National Research Medical University. All Rights Reserved. Rivaroxaban is a safer and more effective alternative to warfarin. However, there are reports of some cases of major hemorrhagic complications associated with rivaroxaban that significantly impair the patients' quality of life and can lead to a fatality. Personalized therapy, including pharmacogenetic testing, may help prevent such adverse events. This study aimed to investigate how ABCB1 3435C>T (rs1045642) and CYP3A5 6986A>G (rs776746) gene polymorphisms, when carried by a patient taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery, affect prothrombin time (PT). Sixty-five patients participated in the study. Their genotypes were identified by PCR in real time. To learn PT peculiar to each patient, we collected venous blood on the 5 th day of their anticoagulation therapy, 1 hour before they took rivaroxaban and 3 hours after. Having calculated %∆PT, we divided the patients into 2 groups: 1) %∆PT ≤ 0 (n = 7; 10.8%); 2) %∆PT > 0 (n = 58; 89.2%). Regarding the distribution of rs1045642 polymorphism, we determined the difference between the groups to be statistically significant (χ 2 = 6.64; p = 0.027). As for rs776746 polymorphism, the difference was insignificant (χ 2 = 0.101; p = 1.0). We discovered that rs1045642 polymorphism has a significant effect on PT variance in patients taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery.
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Increased thrombin generation as a potential marker for adverse pregnancy outcomes
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01.01.2018 |
Gribkova I.
Koroleva N.
Davydovskaya M.
Murashko A.
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Akusherstvo i Ginekologiya (Russian Federation) |
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0 |
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© 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.
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