Enhanced Thrombin Regulation during Warfarin Therapy in Children Compared to Adults

Patricia Massicotte; Michael Leaker; Velma Marzinotto; Margaret Adams; Robert Freedom; William Williams; Patsy Vegh; Leslie Berry; Bianca Shah; Maureen Andrew

doi:10.1055/s-0037-1615422

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 80(04): 570-574
DOI: 10.1055/s-0037-1615422

Rapid Communication

Schattauer GmbH

Enhanced Thrombin Regulation during Warfarin Therapy in Children Compared to Adults^[*]

Autoren

Patricia Massicotte

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Michael Leaker

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Velma Marzinotto

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Margaret Adams

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Robert Freedom

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
William Williams

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Patsy Vegh

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Leslie Berry

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Bianca Shah

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Maureen Andrew

¹From the Departments of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario, and Divisions of Hematology, Cardiology, and Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada

Abstract

Summary

The intensity of warfarin therapy for prevention of primary and secondary thromboembolic complications in paediatric patients, is extrapolated from guidelines for adults, which may not be optimal. Therefore, we assessed thrombin regulation ex vivo and in vitro in plasmas from 40 children (1 to 18 years old with a median age of 13 years) and 27 adults receiving warfarin with an international normalized ratio of 2 to 3 (child: 2.5 ± 0.15; adult: 2.4 ± 0.14). Ex vivo concentrations of prothrombin fragment 1.2 were significantly lower in children (0.30 ± 0.03 nM) compared to adults (0.45 ± 0.04 nM; p <0.01). Thrombin generation in defibrinated plasmas (Arvin) was decreased and delayed for children compared to adults when activated by either activated partial thromboplastin time (child = 32 ± 1.7, adult = 45 ± 1.9 μM · s) or prothrombin time (child = 35 ± 0.7, adult = 46 ± 1.0 μM · s) reagents (p <0.01 for both). Although plasma concentrations of factors (F) II, FVII, FIX, F X, protein C and protein S were similar, more of the thrombin generated was complexed to α₂ macroglobulin (α₂M) at times close to peak thrombin activity (60 s) in plasma from children (general linear analysis of variance; p <0.03). Thus, increased α₂M levels may enhance thrombin regulation in paediatric compared to adult patients receiving warfarin, suggesting that clinical trials in children, using less intense warfarin treatment, may be required to determine optimum therapy.

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Referenzen

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Enhanced Thrombin Regulation during Warfarin Therapy in Children Compared to Adults[*]

Autoren

Enhanced Thrombin Regulation during Warfarin Therapy in Children Compared to Adults^[*]