title: Factor X deficiency and intracranial bleeding: who is at risk?
abstract: Very few mutations of the gene encoding for coagulation factor X (FX) have been found associated with intracranial haemorrhage (ICH) due to FX deficiency (FXD). No guidelines exist as to when prophylaxis in FXD should be started and how patients at risk for ICH can be identified. We report on a novel mutation causative for ICH in a family of Iranian origin and provide a summary of all published mutations in the FX gene related to ICH. The index patient is an infant with umbilical bleeding requiring blood transfusion in the postnatal period. The international normalized ratio (6.01) and activated partial thromboplastin time (117 s) were prolonged. Coagulation factor analysis was normal except for FX activity (<1%). At 4 months, the child suffered a spontaneous severe intracranial haemorrhage. The child was the product of a consanguineous union. Four of five available family members from three generations displayed minor bleeding symptoms and mildly reduced FX. Sequencing of FX gene demonstrated homozygosity for a novel duplication A (c.1402_1403dupA)* in exon 8 and heterozygosity in four family members. We compare this case to all 15 patients with FXD and ICH and their 11 known mutations described so far. This case illustrates a pattern of FXD (a male neonate with umbilical or gastrointestinal bleeding, very low FX:C (<1%) and an underlying homozygous genotype) who may be at high risk for ICH. In these cases, we recommend to start early prophylactic substitution of FX to prevent a possible life-threatening haemorrhage.
authors.affiliation: Department of Paediatrics, University of Western ON, London, Ontario, Canada. Ralf.Rauch@lhsc.on.ca
authors.forename: R
authors.initials: R
authors.lastname: Rauch
authors.forename: M
authors.initials: M
authors.lastname: Girisch
authors.forename: G
authors.initials: G
authors.lastname: Wiegand
authors.forename: W
authors.initials: W
authors.lastname: Schroeder
authors.forename: M
authors.initials: M
authors.lastname: Hofbeck
authors.forename: E
authors.initials: E
authors.lastname: Welisch
authors.forename: K
authors.initials: K
authors.lastname: Wulff
mesh_terms: D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005170:Factor X / Q000235:genetics*; D005171:Factor X Deficiency / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D020300:Intracranial Hemorrhages / Q000235:genetics*; D007492:Iran; D008297:Male; D009154:Mutation
chemical_list: D005170:Factor X