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Thromb Haemost 1998; 80(04): 570-574
DOI: 10.1055/s-0037-1615422
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Enhanced Thrombin Regulation during Warfarin Therapy in Children Compared to Adults[*]

Patricia Massicotte
1   From 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
1   From 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
1   From 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
1   From 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
1   From 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
1   From 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
1   From 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
1   From 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
1   From 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
1   From 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
› Author Affiliations
Further Information

Publication History

Received 08 August 1997

Accepted after revision 02 July 1998

Publication Date:
27 December 2017 (online)

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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.

* This work was supported by a grant from the Heart and Stroke Foundation of Ontario. Dr. Massicotte is a fellow of the Heart and Stroke Foundation of Ontario, and Dr. Andrew is a Career Scientist with the Heart and Stroke Foundation of Canada.


 

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