Symptomatic Onset of Severe Hemophilia A in Childhood is Dependent on the Presence of Prothrombotic Risk Factors

C. Escuriola Ettingshausen; S. Halimeh; K. Kurnik; R. Schobess; C. Wermes; R. Junker; W. Kreuz; H. Pollmann; U. Nowak-Göttl

doi:10.1055/s-0037-1615679

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(02): 218-200
DOI: 10.1055/s-0037-1615679

Review Article

Schattauer GmbH

Symptomatic Onset of Severe Hemophilia A in Childhood is Dependent on the Presence of Prothrombotic Risk Factors

Authors

C. Escuriola Ettingshausen^*

¹Pediatric Hematology and Oncology, University Hospital Frankfurt, Germany
S. Halimeh

²Pediatric Hematology and Oncology, University Hospital Münster, Germany
K. Kurnik

³Department of Pediatrics, University Hospital Munich, Germany
R. Schobess

⁴Pediatric Hematology and Oncology, University Hospital Halle/Saale, Germany
C. Wermes

⁵Department of Hematology, University Hospital Hannover, Germany
R. Junker

⁶Institute of Clinical Chemistry and Laboratory Medicine and Institute of Arteriosclerosis Research, University of Münster, Germany
W. Kreuz^*

¹Pediatric Hematology and Oncology, University Hospital Frankfurt, Germany
H. Pollmann

²Pediatric Hematology and Oncology, University Hospital Münster, Germany
U. Nowak-Göttl

²Pediatric Hematology and Oncology, University Hospital Münster, Germany

Abstract

Summary

It has been recently suggested that the clinical phenotype of severe hemophilia A (HA) is influenced by co-inheritance with the factor V G1691A mutation. We therefore investigated 124 pediatric PUP patients with hemophilia (A: n = 111) consecutively admitted to German pediatric hemophilia treatment centers. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, antithrombin, protein C, protein S and anti-thrombin were investigated. 92 out of 111 HA patients (F VIII activity < 1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe HA was no different from previously reported data: FV G1691A 6.5%, PT G20201A 3.2%, and protein C type I deficiency 1.1%. No deficiency states of antithrombin or protein S were found in this cohort of hemophilic patients. The first symptomatic bleeding leading to diagnosis of severe hemophilia (< 1%) occurred with a median (range) age of 1.6 years (0.5-7.1) in children carrying defects within the protein C pathway or the PT gene mutation compared with non-carriers of prothrombotic risk factors (0.9 years (0.1-4.0; p = 0.01). The cumulative event-free bleeding survival was significantly prolonged in children carrying additionally prothrombotic defects (log-rank/Mantel-Cox: p = 0.0098). In conclusion, data of this multicenter cohort study clearly demonstrate that the first symptomatic bleeding onset in children with severe HA carrying prothrombotic risk factors is significantly later in life than in non-carriers.

Keywords

Severe hemophilia A - pediatric PUP patients - factor V G1691A - prothrombin G20210A

Full Text

References

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