Haemophilia and thrombophilia

Summary

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. Conclusion: 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.

Zusammenfassung

In dieser multizentrischen Kohortenstudie wurden 135 deutsche Kinder mit Erstmanifestation einer Hämophilie auf folgende prothrombotische Risikofaktoren untersucht: Faktor V (FV) G1691A, Faktor II (FII) G20210A, Methylentetrahydrofolatreduktase (MTHFR) T677T, Lipoprotein a (Lp a), Antithrombin, Protein C, Protein S. 103 von 122 Patienten mit Hämophilie A (HA) litten an einer schweren Hämophilieform (Faktor-VIIIC-Restaktivität <1%). Die Prävalenz der untersuchten prothrombotischen Risikofaktoren unterschied sich nicht von der in der gesunden Bevölkerung: FV GA 5,8%, FII GA 3,9%, MTHFR TT 10%, erhöhte Werte für Lp a 7%, Protein-C-Typ-I-Mangel 1,0%. Die erste, zur Diagnose der schweren Hämophilie A (HA) führende Blutung wurde im Alter von 1,6 Jahren (0,5-7,1 Jahre) bei Kindern mit prothrombotischen Risikofaktoren deutlich früher beobachtet als bei Patienten mit alleiniger schwerer HA (0,9 Jahre: 0,1-4,0 Jahre; p = 0,01). Zwei Patienten mit neonatalem Schlaganfall (prothrombotische Risikofaktoren: Lp a, FII GA) erlitten eine hämorrhagische Transformation ihres Schlaganfallareals im Rahmen einer schweren Hämophilie. Acht von 25 Kindern mit zentralen Venenkathetern (implantiert zur Substitution von Faktor-VIII-Konzentraten) erlitten katheterinduzierte Thrombosen nach Korrektur der Hämophilie. Schlussfolgergung: Die Daten dieser multizentrischen Kohortenstudie weisen darauf hin, dass der klinische Phänotyp der schweren HA durch die Koexpression von weiteren prothrombotischen Risikofaktoren beeinflusst werden kann.

Keywords

Severe haemophilia A - pediatric PUP patients - factor V G1691A - factor II G20210A

Schlüsselwörter

Hämophilie A - pädiatrische PUP-Patienten - Faktor-V-G1691A-Mutation - Prothrombin-G20210A-Mutation

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