title: Haemophilia and thrombophilia. What do we learn about combined inheritance of both genetic variations?
abstract: For the study presented here 135 pediatric PUP patients with haemophilia consecutively admitted to German pediatric haemophilia treatment centers were investigated. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the factor II (FII) G20210A variant, methylenetetrahydrofolate reductase (MTHFR) T677T genotype, elevated lipoprotein a (Lp a), antithrombin, protein C, and protein S were investigated. 103 out of 122 HA patients (FVIII activity <1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe haemophilia A (HA) did not differ from previously reported data: FV GA 5.8%, FII GA 3.9%, MTHFR TT 10%, elevated Lp a 7%, protein C type I deficiency 1.1%. The first symptomatic bleeding leading to diagnosis of severe haemophilia occurred with a median age of 1.6 years (range: 0.5-7.1 years) in children carrying prothrombotic risk factors compared to non-carriers (0.9 years (0.1-4.0; p = 0.01). Two patients presenting with neonatal stroke due to elevated Lp a and the FII GA variant showed haemorrhagic stroke transformation triggered by severe haemophilia. In addition, when haemophilia A was corrected by administration of factor VIII concentrates eight out of 25 children with central lines in place developed catheter-related thrombosis.
  
  
  CONCLUSIONS
  The data of this multicentre cohort study demonstrate that the clinical phenotype of severe haemophilia A in childhood is clearly influenced by the coinheritance of prothrombotic risk factors.
authors.affiliation: Pediatric Hematology/Oncology, University of Münster, Albert-Schweitzer-Str. 33, 48149 Münster, Germany. leagottl@uni-muenster.de
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
authors.forename: C
authors.initials: C
authors.lastname: Escuriola
authors.forename: K
authors.initials: K
authors.lastname: Kurnik
authors.forename: R
authors.initials: R
authors.lastname: Schobess
authors.forename: S
authors.initials: S
authors.lastname: Horneff
authors.forename: A
authors.initials: A
authors.lastname: Kosch
authors.forename: W
authors.initials: W
authors.lastname: Kreuz
authors.forename: H
authors.initials: H
authors.lastname: Pollmann
mesh_terms: D001798:Blood Proteins / Q000235:genetics; D005169:Factor VIII / Q000235:genetics; D005838:Genotype; D006467:Hemophilia A / Q000097:blood / Q000150:complications* / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011336:Probability; D011516:Prothrombin / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology; D019851:Thrombophilia / Q000097:blood / Q000150:complications* / Q000235:genetics*
chemical_list: D001798:Blood Proteins; D011516:Prothrombin; D005169:Factor VIII