Skip to main content


Log in

Genetic analysis of a compound heterozygous patient with congenital factor X deficiency and regular replacement therapy with a prothrombin complex concentrate

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript


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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


  1. 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.

    Article  CAS  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. Menegatti M, Peyvandi F. Treatment of rare factor deficiencies other than hemophilia. Blood. 2019;133:415–24.

    Article  CAS  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. 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.

    Article  CAS  Google Scholar 

  7. Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost. 2009;35:407–15.

    Article  CAS  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. Peyvandi F, Menegatti M. Treatment of rare factor deficiencies in 2016. Am Soc Hematol Educ Program. 2016;2016:663–9.

    Article  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. Franchini M, Lippi G. Prothrombin complex concentrates: an update. Blood Transfus. 2010;8:149–54.

    PubMed  PubMed Central  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. Peyvandi F, Garagiola I, Biguzzi E. Advances in the treatment of bleeding disorders. J Thromb Haemost. 2016;14:2095–106.

    Article  CAS  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. Kouides PA, Kulzer L. Prophylactic treatment of severe factor X deficiency with prothrombin complex concentrate. Haemophilia. 2001;7:220–3.

    Article  CAS  Google Scholar 

  17. 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.

    Article  CAS  Google Scholar 

  18. 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.

    Article  CAS  Google Scholar 

  19. 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.

    Article  CAS  Google Scholar 

Download references


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).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Eriko Morishita.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: