Congenital FXIII Research Articles

Rare Congenital Coagulation Factor Deficiencies: Clinical Manifestations

The clinical symptoms of rare bleeding disorders (RBDs) range from mucosal to life-threatening haemorrhages or functionally restricting haemorrhages. Congenital coagulation factor (F) deficiencies, VII, FX, FXIII, fibrinogen deficiencies and dysfibrinogenaemias, represent 3‒5% of all inherited coagulation factor deficiencies. Due to this low prevalence and the variability of bleeding manifestations, the clinical features of these RBDs are not well characterised. For this reason we conducted a retrospective multicentre national survey using patient records to characterize clinical bleeding manifestations in patients with congenital isolated/combined coagulation factor deficiencies or with congenital abnormalities of fibrinogen. Fifteen departments (11 haematology and four paediatric departments) across Algeria took part in the study, and data from 234 patients were analyzed. The majority of patients (n=164; 70.1%) had isolated congenital coagulation factor deficiencies, the most common of which was FVII deficiency (n=101; 43.2%). Only 221 patients (9.0%) had combined congenital coagulation deficiencies, the most common of which was FVIII/V deficiency (n=13; 5.6%). Congenital fibrinogen abnormalities were reported in 49 patients (20.9%). Overall, there were 327 bleeding episodes in 163 patients. The majority of bleeding episodes (n=195, 59.6%) were in patients with an isolated factor deficiency, the highest incidence of which was recorded for FVII deficient patients (95 bleeds; mean 1.7 bleeds/patient). Our results support existing descriptions in the literature and may help to target resourcing and plan treatment strategies for those patients at most risk of bleeding.

Molecular characterization of a novel mutation in the factor XIII a subunit gene associated with a severe defect: importance of prophylactic substitution

A congenital FXIII A subunit deficiency was diagnosed in a male child because of umbilical bleeding at birth. Venous infusion was difficult and prophylactic FXIII infusion was delayed. At age 1, he suffered a spontaneous intracranial haemorrhage. Substitutive FXIII was initiated, and at age 12, no other significant bleeding event had occurred. His 5 years younger brother also bears the same FXIII deficiency. The younger brother's treatment was initiated at birth and never discontinued, and no bleeding occurred. Mutation gene analysis found a homozygous four bases insertion predicting a stop codon seven residues after PRO675. Antigen assay indicated that the mutant molecule is secreted. This case highlights the importance of prophylactic FXIII infusion.