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

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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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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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Correspondence to Eriko Morishita.

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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

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