Use of plasma-derived factor X concentrate in neonates and infants with congenital factor X deficiency.
blood coagulation disorder
factor X deficiency
hemostasis
infant/newborn
secondary prevention
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
17
01
2020
revised:
29
05
2020
accepted:
23
06
2020
pubmed:
3
7
2020
medline:
15
5
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
Congenital factor X deficiency (FXD) is a rare bleeding disorder that often presents with severe bleeding in the neonatal period. Long-term prophylaxis with infusions of FX-containing products is recommended in patients with FXD and a personal or family history of severe bleeding. A plasma-derived FX concentrate (pdFX) is approved for on-demand and prophylactic therapy in adults and children with FXD. The safety and efficacy of pdFX has been demonstrated in patients <12 years of age, yet limited data exist regarding its use in infants. This retrospective case series details clinical experience using pdFX in four neonates with moderate and severe FXD across four institutions. All four patients presented in the first week of life with severe bleeding. Following treatment of the acute bleed, prophylactic pdFX was initiated at an average of 29 days of life and a dose of 69 IU/kg every 48 hours. Incremental recovery (IR) in three infants averaged 1.42 IU/dL per IU/kg (min-max: 1.06-1.67 IU/dL per IU/kg). One patient experienced thrombotic complications in the setting of sepsis. After a median follow-up of 26.5 months, no patient has experienced breakthrough bleeding episodes. Our study supports the use of pdFX in neonates and infants and suggests that higher pdFX dosing of 70 to 80 IU/kg every 48 hours based on the smallest available vial size is feasible. Because of variability in IR, close monitoring of FX activity should be used to guide dosing in this age group.
Sections du résumé
BACKGROUND
Congenital factor X deficiency (FXD) is a rare bleeding disorder that often presents with severe bleeding in the neonatal period. Long-term prophylaxis with infusions of FX-containing products is recommended in patients with FXD and a personal or family history of severe bleeding. A plasma-derived FX concentrate (pdFX) is approved for on-demand and prophylactic therapy in adults and children with FXD. The safety and efficacy of pdFX has been demonstrated in patients <12 years of age, yet limited data exist regarding its use in infants.
PATIENTS/METHODS
This retrospective case series details clinical experience using pdFX in four neonates with moderate and severe FXD across four institutions.
RESULTS AND CONCLUSIONS
All four patients presented in the first week of life with severe bleeding. Following treatment of the acute bleed, prophylactic pdFX was initiated at an average of 29 days of life and a dose of 69 IU/kg every 48 hours. Incremental recovery (IR) in three infants averaged 1.42 IU/dL per IU/kg (min-max: 1.06-1.67 IU/dL per IU/kg). One patient experienced thrombotic complications in the setting of sepsis. After a median follow-up of 26.5 months, no patient has experienced breakthrough bleeding episodes. Our study supports the use of pdFX in neonates and infants and suggests that higher pdFX dosing of 70 to 80 IU/kg every 48 hours based on the smallest available vial size is feasible. Because of variability in IR, close monitoring of FX activity should be used to guide dosing in this age group.
Identifiants
pubmed: 32613702
doi: 10.1111/jth.14985
pii: S1538-7836(22)01166-7
doi:
Substances chimiques
Factor X
9001-29-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2551-2556Informations de copyright
© 2020 International Society on Thrombosis and Haemostasis.
Références
Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost. 2009;35(04):407-415.
Peyvandi F, Mannucci PM, Lak M, Abdoullahi M, Zeinali S, Sharifian R, Perry D. Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients. Br J Haematol. 1998;102(2):626-628.
Peyvandi F, Palla R, Menegatti M, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost. 2012;10(4):615-621.
Peyvandi F, Menegatti M, Palla R. Rare bleeding disorders: worldwide efforts for classification, diagnosis, and management. Semin Thromb Hemost. 2013;39(06):579-584.
Karimi M, Vafafar A, Haghpanah S, et al. Efficacy of prophylaxis and genotype-phenotype correlation in patients with severe factor X deficiency in Iran. Haemophilia. 2012;18(2):211-215.
McMahon C, Smith J, Goonan C, Byrne M, Smith OP. The role of primary prophylactic factor replacement therapy in children with severe factor X deficiency. Br J Haematol. 2002;119(3):789-791.
Mumford AD, Ackroyd S, Alikhan R, et al. Guideline for the diagnosis and management of the rare coagulation disorders: a United Kingdom Haemophilia Centre Doctors' Organization guideline on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2014;167(3):304-326.
Brown DL, Kouides PA. Diagnosis and treatment of inherited factor X deficiency. Haemophilia. 2008;14(6):1176-1182.
Austin SK, Brindley C, Kavakli K, Norton M, Shapiro A. Pharmacokinetics of a high-purity plasma-derived factor X concentrate in subjects with moderate or severe hereditary factor X deficiency. Haemophilia. 2016;22(3):426-432.
Austin SK, Kavakli K, Norton M, Peyvandi F, Shapiro A, the Group IFX. Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency. Haemophilia. 2016;22(3):419-425.
Escobar MA, Auerswald G, Austin S, Huang JN, Norton M, Millar CM. Experience of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency undergoing surgery. Haemophilia. 2016;22(5):713-720.
Kulkarni R, James AH, Norton M, Shapiro A. Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency. J Thromb Haemost. 2018;16(5):849-857.
Shapiro A. Plasma-derived human factor X concentrate for on-demand and perioperative treatment in factor X-deficient patients: pharmacology, pharmacokinetics, efficacy, and safety. Expert Opin Drug Metab Toxicol. 2016;13(1):97-104.
Liesner R, Akanezi C, Norton M, Payne J. Prophylactic treatment of bleeding episodes in children <12 years with moderate to severe hereditary factor X deficiency (FXD): Efficacy and safety of a high-purity plasma-derived factor X (pdFX) concentrate. Haemophilia. 2018;24(6):941-949.
Huang JN, Liesner R, Akenezi C, Austin SK, Kavakli K. A multicenter, retrospective data collection study on the compassionate use of a plasma-derived factor X concentrate to treat patients with hereditary factor X deficiency. Blood. 2017;130(Suppl 1):3736.
Odom MW, Leone G, De Stefano V, et al. Five novel point mutations: two causing haemophilia B and three causing factor X deficiency. Mol Cell Probes. 1994;8(1):63-65.
Ferrarese M, Baroni M, Valle P, et al. Missense changes in the catalytic domain of coagulation factor X account for minimal function preventing a perinatal lethal condition. Haemophilia. 2019;25(4):685-692.
US Food and Drug Administration. Clinical Review - Coagadex. https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/coagadex
Grottke O, Moser O, Farrag A, Elbracht M, Orlikowsky T, Trepels-Kottek S. Plasma-derived factor X therapy for treatment of intracranial bleeding in a patient with factor X deficiency: a case report. Transfusion. 2019;59(7):2228-2233.
Shapiro AD, Korth-Bradley J, Poon MC. Use of pharmacokinetics in the coagulation factor treatment of patients with haemophilia. Haemophilia. 2005;11(6):571-582.
Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004;104(5):1243-1252.
Palla R, Peyvandi F, Shapiro AD. Rare bleeding disorders: diagnosis and treatment. Blood. 2015;125(13):2052-2061.
Diesch T, von der Weid N, Schifferli A, Kühne T. Intracranial hemorrhage as the first manifestation of severe congenital factor X deficiency in a 20-month-old male: case report and review of the literature. Pediatr Blood Cancer. 2016;63(7):1300-1304.