Haemophilia and thrombophilia

 

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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.

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