Abstract
Congenital factor X (FX) deficiency is a rare bleeding disorder with an incidence of one in one million. The proband, a 2-year-old girl, exhibited easy bruising and a history of umbilical cord bleeding at birth. Prothrombin time (> 40 s) and activated partial thromboplastin time (65.0 s) were prolonged. Marked declines in FX activity (< 1%) and FX antigen levels (5%) were also observed. Genetic analysis of the proband identified two types of single-base substitutions, c.353G>A (p.Gly118Asp) and c.1303G>A (p.Gly435Ser), indicating compound heterozygous congenital FX deficiency. Genetic analysis of family members revealed that her father and older sister (5-year-old) were also heterozygous for p.Gly118Asp, and that her mother was heterozygous for p.Gly435Ser. To improve the bleeding tendency, the proband received regular replacement of 500 units of PPSB-HT, a prothrombin complex concentrate (PCC). Following continued regular replacement of 500 units of PPSB-HT once per week, the proband has exhibited no bleeding tendencies and no new bruises have been observed. There are no previous report of the use of PPSB-HT for regular FX replacement. Regular replacement therapy with PPSB-HT may be an effective method for preventative control of bleeding tendencies in FX deficiency.
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References
Nagaya S, Akiyama M, Murakami M, Sekiya A, Asakura H, Morishita E. Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteins. Haemophilia. 2018;24:774–85.
Takabe K, Holman PR, Herbst KD, Glass CA, Bouvet M. Successful perioperative management of factor X deficiency associated with primary amyloidosis. J Gastrointest Surg. 2004;8:358–62.
Menegatti M, Peyvandi F. Treatment of rare factor deficiencies other than hemophilia. Blood. 2019;133:415–24.
Jayandharan G, Viswabandya A, Baidya S, Nair SC, Shaji RV, George B, et al. Six novel mutations including triple heterozygosity for Phe31Ser, 514delT and 516TG factor X gene mutations are responsible for congenital factor X deficiency in patients of Nepali and Indian origin. J Thromb Haemost. 2005;3:1482–7.
Peyvandi F, Menegatti M, Santagostino E, Akhavan S, Uprichard J, Perry DJ, et al. Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency. Br J Haematol. 2002;117:685–92.
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. 2017;13:97–104.
Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost. 2009;35:407–15.
Dorgalaleh A, Zaker F, Tabibian S, Alizadeh S, Dorgalele S, Hosseini S, et al. Spectrum of factor X gene mutations in Iranian patients with congenital factor X deficiency. Blood Coagul Fibrinolysis. 2016;27:324–7.
Peyvandi F, Menegatti M. Treatment of rare factor deficiencies in 2016. Am Soc Hematol Educ Program. 2016;2016:663–9.
Lim MY, McCarthy T, Chen SL, Rollins-Raval MA, Ma AD. Importance of pharmacokinetic studies in the management of acquired factor X deficiency. Eur J Haematol. 2016;96:60–4.
Franchini M, Lippi G. Prothrombin complex concentrates: an update. Blood Transfus. 2010;8:149–54.
Matsuo Y, Mizuochi T, Miho M, Nakagawa S, Ozono S, Ueda K, et al. Factor X deficiency with heterozygous mutations of novel p. G435S and known p. G244R in a patient presenting with severe umbilical hemorrhage. Kurume Med J. 2017;63:23–8.
Peyvandi F, Garagiola I, Biguzzi E. Advances in the treatment of bleeding disorders. J Thromb Haemost. 2016;14:2095–106.
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;16:849–57.
Austin SK, Kavakli K, Norton M, Peyvandi F, Shapiro A, FX Investigators Group. Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency. Haemophilia. 2016;22:419–25.
Kouides PA, Kulzer L. Prophylactic treatment of severe factor X deficiency with prothrombin complex concentrate. Haemophilia. 2001;7:220–3.
Seki M, Koh K, Inoue T, Tomita Y, Kato M, Shimizu M, et al. Prophylactic administration of prothrombin complex concentrates for congenital prothrombin deficiency with a novel frameshift mutation, prothrombin Saitama. Pediatr Blood Cancer. 2013;60:503–5.
Apak H, Celkan T, Ozkan A, Yüksel L, Bilgi Z, Yildiz I. Severe factor X deficiency treated with heparin-added prothrombin complex concentrate. Ann Hematol. 2003;82:710–1.
Liesner R, Akanezi C, Norton M, Payne J. Prophylactic treatment of bleeding episodes in children %3c12 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;24:941–9.
Acknowledgements
This work was supported by grant from the Ministry of Health, Labor and Welfare of Japan (E.M.) (Grant number 6046619-01), the Ministry of Education, Culture, Sports, Science and Technology of Japan (E.M.) (Grant number 18K07442) and Japan Agency for Medical Research and Development (E. M.) (Grant number 19ek0109210h0003).
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Togashi, T., Nagaya, S., Nagasawa, M. et al. Genetic analysis of a compound heterozygous patient with congenital factor X deficiency and regular replacement therapy with a prothrombin complex concentrate. Int J Hematol 111, 51–56 (2020). https://doi.org/10.1007/s12185-019-02767-y
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DOI: https://doi.org/10.1007/s12185-019-02767-y