Emicizumab prophylaxis among infants and toddlers with severe hemophilia A and inhibitors-a single-center cohort.
Antibodies, Bispecific
/ therapeutic use
Antibodies, Monoclonal, Humanized
/ therapeutic use
Blood Loss, Surgical
/ prevention & control
Child, Preschool
Factor IXa
/ immunology
Factor X
/ immunology
Follow-Up Studies
Hemophilia A
/ blood
Hemorrhage
/ etiology
Humans
Infant
Male
Prospective Studies
Thrombelastography
Thrombin
/ analysis
Treatment Outcome
ROTEM
emicizumab
hemophilia A
inhibitors
thrombin generation
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
11
04
2018
revised:
07
05
2019
accepted:
22
05
2019
pubmed:
28
7
2019
medline:
26
2
2020
entrez:
27
7
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Substances chimiques
Antibodies, Bispecific
0
Antibodies, Monoclonal, Humanized
0
emicizumab
7NL2E3F6K3
Factor X
9001-29-0
Factor IXa
EC 3.4.21.22
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Pragmatic Clinical Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
e27886Informations de copyright
© 2019 Wiley Periodicals, Inc.
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