Factor X deficiency: clinical manifestation of 102 subjects from Europe and Latin America with mutations in the factor 10 gene

Abstract

Inherited factor X deficiency (FXD) is a rare (1:1,000,000) recessive bleeding disorder. The clinical and laboratory phenotypes of FXD are poorly correlated and few regional studies on the genotype and the clinical manifestations of FXD are known. To understand the association between clinical manifestations and causative genotype, detailed evaluation of bleeding pattern in a high number of patients is needed. This international study analysed the phenotype and genotype of 102 subjects from Central Europe (Germany, Poland and Slovakia) and Latin America (Costa Rica and Venezuela) with causative mutations in the F10 gene, via sequencing. Twenty-eight homozygous, seven compound-heterozygous and 67 heterozygous FXD subjects were characterized. Twenty-nine different causative mutations, including 15 novel mutations, were analysed. Spontaneous bleeding symptoms in 42 symptomatic individuals (26 homozygous, seven compound heterozygous and nine heterozygous) comprised easy bruising (55%), haematoma (43%), epistaxis (36%), haemarthrosis (33%), intracranial haemorrhage (ICH; 21%), and gastrointestinal (GI) haemorrhage (12%). The manifestation of bleeding symptoms in 9 of 67 (13%) symptomatic heterozygous subjects is described. The bleeding patterns of the enrolled patients showed differences that are associated with the types of F10 mutation, and the corresponding genotypes. The homozygous patients were evaluated for genotype-phenotype correlation. The results suggested that ICH seems to be associated with the F10 mutation Gly380Arg, and possibly with the mutations IVS7-1G>A and Tyr163delAT. A tentative association of other mutations to severe symptoms such as haemarthrosis and GI haemorrhage is reported. The severity of FXD, the genotype-phenotype association, and the results of regional studies are discussed.

Rare Bleeding Disorders are not so Rare in Pakistan

“…Another 2 patients had recurrent gum bleeding, hematoma, umbilical cord bleeding, hemarthrosis and easy bruising (Table 1). These clinical findings are comparable to those observed in FX deficient Indian, European and South American patients [16] where muco-cutaneous bleeds were 82% with ecchymosis occurring more frequently than epistaxis [13]. However we had less FX deficient patients (6%) in our study.…”

An analysis of 8 cases of factor X deficiency

“…Intracranial bleeding is also reported previously, particularly in infants [9]. Herrmann FH et al reported high incidence (21%) of intracranial bleeding in homozygotes as well as heterozygotes [2]. Our series also has very high incidence of intracranial bleeding (2 out of 8 cases, 25%).…”

“…Males and females are equally affected [1]. Clinical manifestation of factor X defi ciency is related to the functional level of factor X and genetic mutation [2]. In severe defi ciency, (factor X level less than 1% of normal), patient bleeds spontaneously as well as following trauma [3,4].…”

Treatment of acquired factor X inhibitor by plasma exchange with concomitant intravenous immunoglobulin and corticosteroids

“…Inherited factor X deficiency has been reported to have an incidence of 1:1,000,000 [1,2]. Acquired factor X deficiency is even rarer and is associated with amyloidosis in the majority of cases [3].…”