title: Central nervous system bleeding in pediatric patients with factor XIII deficiency: a study on 23 new cases.
abstract: BACKGROUND
  Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder, which has the highest incidence in Sistan and Baluchistan Province in Iran, compared to its overall incidence around the world. This disorder has different clinical manifestations ranging from mild bleeding tendency to lethal bleeding episodes including central nervous system (CNS) hemorrhage. The aim of this study was to evaluate the demographic data, pattern of CNS bleeding, and the role of plasminogen activator inhibitor-1 (PAI-1) (PAI-1) 4G/5G and thrombin activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphisms in intracranial and extracranial hemorrhages in 23 new cases of FXIII-deficient subjects.
  
  
  METHODS
  This case-control study was conducted on 23 FXIII-deficient patients with CNS bleeding episodes and 23 patients as the control group with FXIII deficiency but without any history of CNS bleeding. Initially, to confirm the molecular defect, both groups were evaluated for the most frequently reported mutation of FXIII (Trp187Arg mutation) in a previous study in Sistan and Baluchistan Province. Then, demographic data, clinical manifestations, and pattern of CNS bleeding were determined. Eventually, the patients were assessed for PAI-14G/5G and TAFI Thr325Ile polymorphisms.
  
  
  RESULTS
  The results of this study revealed that all the subjects (including the case and control groups) were homozygous for Trp187Arg mutation. Nineteen patients (82.6%) had intracranial hemorrhage (ICH) and four patients (17.4%) had extracranial hemorrhage (ECH). Intraparenchymal hemorrhage was the most common form of ICH (89.5%), and epidural hemorrhage was observed in two patients (10.5%). Anatomic regions in patients with intraparenchymal hemorrhage were temporal in six (35.3%), occipital in four (23.5%), diffused intraparenchymal in four (23.5%), temporal-occipital in two (11.8%), and subdural with temporal in one (5.9%) patient. We found that in the case group, 14 patients (60.8%) were homozygous for TAFI Thr325Ile polymorphism and 8 cases (34.7%) were heterozygous. In the control group, 4 (17.4%) and 13 (56.5%) patients were homozygous and heterozygous, respectively (P < 0.001 vs. P < 0.01).We also found that an equal number of patients (two individuals) in the case and control groups (8.7% in each group) were heterozygous for PAI-14G/5G polymorphism.
  
  
  CONCLUSIONS
  It seems that PAI-14G/5G polymorphism does not have any effect on occurrence of ICH and ECH in patients with FXIII deficiency, while TAFI Thr325Ile is a strong genetic risk factor (odds ratio:14.9, 95% confidence interval: 7.4-31.1).
authors.forename: Majid
authors.initials: M
authors.lastname: Naderi
authors.forename: Shaban
authors.initials: S
authors.lastname: Alizadeh
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kazemi
authors.forename: Shadi
authors.initials: S
authors.lastname: Tabibian
authors.forename: Farhad
authors.initials: F
authors.lastname: Zaker
authors.forename: Taregh
authors.initials: T
authors.lastname: Bamedi
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kashani Khatib
authors.forename: Akbar
authors.initials: A
authors.lastname: Dorgalaleh
mesh_terms: D025901:Carboxypeptidase B2 / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D002490:Central Nervous System / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002648:Child; D005176:Factor XIII / Q000235:genetics*; D005177:Factor XIII Deficiency / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020300:Intracranial Hemorrhages / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D005176:Factor XIII; D025901:Carboxypeptidase B2
keywords: CNS bleeding; Extracranial hemorrhage; FXIII deficiency; Intracranial hemorrhage