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Thromb Haemost 1994; 71(03): 265-269
DOI: 10.1055/s-0038-1642427
Original Article
Schattauer GmbH Stuttgart

Oral Anticoagulation Therapy in Pediatric Patients: a Prospective Study

Maureen Andrew
The Department of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario and Divisions of Hematology, Cardiology, Surgery and Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Velma Marzinotto
The Department of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario and Divisions of Hematology, Cardiology, Surgery and Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Lu Ann Brooker
The Department of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario and Divisions of Hematology, Cardiology, Surgery and Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Margaret Adams
The Department of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario and Divisions of Hematology, Cardiology, Surgery and Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Jeff Ginsberg
The Department of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario and Divisions of Hematology, Cardiology, Surgery and Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Robert Freedom
The Department of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario and Divisions of Hematology, Cardiology, Surgery and Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
,
William Williams
The Department of Pediatrics and Pathology and Division of Hematology/Oncology, McMaster University, Hamilton, Ontario and Divisions of Hematology, Cardiology, Surgery and Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Received: 06 July 1993

Accepted after revision 23 December 1993

Publication Date:
06 July 2018 (online)

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Summary

There are no validated guidelines for administering or monitoring oral anticoagulant therapy in pediatric patients. A pediatric thromboembolism program at the Hospital for Sick Children, Toronto, prospectively monitored consecutive children requiring warfarin over an 18 month period. A uniform protocol was followed and dose adjustments based upon international normalized ratios (INRs). One hundred and fifteen consecutive children; 68 males and 47 females, received warfarin. The age distribution was: <ly (19); 1-5 ys (33); 6-10ys (20); 11-18 ys (43). Warfarin was used for secondary prevention of venous thromboembolism (n = 56) and primary prevention of thromboembolism (n = 59). Underlying disorders included: congenital heart disease (CHD) without mechanical valves (MV) (49); CHD with MV (18); cancer (8); longterm total parenteral nutrition (7); renal disorders (10); other (23). Treatment length was considered as short term (3-6 mths) n = 37 (32%); longterm (> 6 mths) n = 38 (33%); and lifelong n = 40 (35%) of children. While receiving warfarin, 95 children received concurrent longterm treatment with other drugs: 1 drug (28); 2 drugs (27); 3 drugs (21); 4 or more drugs (19).

The amounts of warfarin/kg required to achieve INRs of 2 to 3 decreased with increasing age. Children <1 year of age required 0.32 ± 0.05 mg/kg whereas children 11-18 yrs required 0.09 ± 0.01 mg/kg; P <0.001. Monitoring warfarin required an average of 4.0 measurements per month and 1.5 dose changes per month. Changes in warfarin doses were primarily precipitated by drugs, intermittent illness, and changes in diet. A subgroup of children (n = 21) were treated with low dose warfarin either alone (n = 14) or following a course of full dose therapy (n = 7) to achieve an INR of 1.3 to 1.8. These children had persisting predisposing causes for new or recurrent thromboembolism. After the age of 1, the average dose required was 0.08 ± 0.01 mg/kg.

Complications were rare. Two children had significant bleeding events that resolved without further morbidity. There were no recurrent thrombotic events while children were receiving warfarin. In summary, warfarin therapy is age and weight dependent in children; close monitoring is necessary because of changing requirements; and complications are infrequent when management is coordinated through one service.

 

  • References

  • 1 David M, Andrew M. Venous thromboembolism complications in children: A critical review of the literature. J Pediatr 1992. (in press).
    Search in Google Scholar
  • 2 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80 (08) 1998-2005
    CrossrefPubMedSearch in Google Scholar
  • 3 Andrew M, Marzinotto V, Blanchette V, Ginsberg J, Burrows P, Benson L, Williams W, David M, Poon A, Sparling K. Heparin therapy in pediatric patients: A prospective cohort study. Pediatr Res 1993. (in press).
    Search in Google Scholar
  • 4 Doyle JJ, Koren G, Chen MY, Blanchette VS. Anticoagulation with sodium warfarin in children: Effect of a loading regimen. J Pediatr 1988; 113: 1095-7
    CrossrefPubMedSearch in Google Scholar
  • 5 Carpentieri U, Nghiem QX, Harris LC. Clinical experience with an oral anticoagulant in children. Arch Dis Child 1976; 51: 445-8
    CrossrefPubMedSearch in Google Scholar
  • 6 Evans DI K, Rowlands M, Poller L. Survey of oral anticoagulant treatment in children. J Clin Pathol 1992; 45: 707-8
    CrossrefPubMedSearch in Google Scholar
  • 7 Hirsh J. Oral anticoagulant drugs. Review article. N Engl J Med 1991; 324: 1865
    CrossrefPubMedSearch in Google Scholar
  • 8 Bradley LM, Midglev FM, Watson DC. et al. Anticoagulation therapy in children with mechanical prosthetic cardiac valves. Am J Cardiol 1985; 56: 533-5
    CrossrefPubMedSearch in Google Scholar
  • 9 Woods A, Vargas J, Berri G, Kreutzer G, Meschengieser S, Lazzari MA. Antithrombotic therapy in children and adolescents. Thromb Res 1986; 42 (03) 289-301
    CrossrefPubMedSearch in Google Scholar
  • 10 Lehman ME, Kolb KW, Barnhart GR, Wagman LD, Barr WH. Warfarin absorption in a patient with short-bowel syndrome. Clin Pharm 1985; 4: 325-6
    PubMedSearch in Google Scholar
  • 11 Kuhn TA, Garnett WR, Wells BK, Karnes HT. Recovery of warfarin from an enteral nutrient formula. Am J Hosp Pharm 1989; 46: 1395-9
    PubMedSearch in Google Scholar
  • 12 Andrew M, Vegh PA, Mitchell LG. Thrombin (IIa) regulation in children differs from adults both in the absence and presence of heparin. Thromb Haemostas 1993. (Abstract).
    Search in Google Scholar
  • 13 Bern MM, Lokich JJ, Wallach SR, Bothe Jr A, Benotti PN, Arkin CF, Greco FA, Huberman M, Moore C. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med 1990; 112: 423-8
    CrossrefPubMedSearch in Google Scholar
  • 14 Fordyce MJ, Baker AS, Staddon GE. Efficacy of fixed minidose warfarin prophylaxis in total hip replacement. BMJ 1991; 303: 219-20
    CrossrefPubMedSearch in Google Scholar
  • 15 Poller L, McKernan A, Thomson JM, Eistein M, Hirsch PJ, Jones JB. Fixed minidose warfarin: a new approach to prophylaxis against venous thrombosis after major surgery. BMJ 1987; 295: 1309-12
    CrossrefPubMedSearch in Google Scholar
  • 16 Kumar S, Haigh JR M, Rhodes LE, Peaker S, Davies JA, Roberts BE, Feely MP. Poor compliance is a major factor in unstable outpatient control of anticoagulant therapy. Thromb Haemostas 1989; 62 (02) 729-32
    PubMedSearch in Google Scholar
  • 17 Stewart S, Cianciotta D, Alexson C, Manning J. The longterm risk of warfarin sodium therapy and the incidence of thromboembolism in children after prosthetic cardiac valves. J Thorac Cardiovasc Surg 1987; 93: 551-4
    PubMedSearch in Google Scholar
  • 18 El Makhlouf A, Friedli B, Oberhansli I. et al. Prosthetic heart valve replacement in children. J Thorac Cardiovasc Surg 1987; 93: 80-5
    PubMedSearch in Google Scholar
  • 19 Sade RM, Crawford Jr FA, Fyfe DA, Stroud MR. Valve protheses in children: A reassessment of anticoagulation. J Thorac Cardiovasc Surg 1988; 95 (04) 553-61
    PubMedSearch in Google Scholar
  • 20 Rao S, Solymar L, Mardini MK, Fawzy ME, Guinn G. Anticoagulant therapy in children with prosthetic valves. Ann Thorac Surg 1989; 47: 589-92
    CrossrefPubMedSearch in Google Scholar
  • 21 Serra AJ S, McNicholas KW, Olivier Jr HF, Boe SL, Lemole GM. The choice of anticoagulation in pediatric patients with the St. Jude Medical valve prostheses. J Cardiovasc Surg 1987; 28: 588-91
    PubMedSearch in Google Scholar
  • 22 McGrath LB, Gonzalez-Lavin L, Edlredge WJ, Colombi M, Restrepo D. Thromboembolic and other events following valve replacement in a pediatric population treated with antiplatelet agents. Ann Thorac Surg 1987; 43: 285-7
    CrossrefPubMedSearch in Google Scholar
  • 23 Spevak PJ, Freed MD, Castaneda AR. et al. Valve replacement in children less than 5 years of age. J Am Cardiol 1986; 8: 901-8
    CrossrefPubMedSearch in Google Scholar
  • 24 Harada Y, Imai Y, Kurosawa H. et al. Ten-year follow-up after valve replacement with the St. Jude Medical prosthesis in children. J Thorac Cardiovasc Surg 1990; 100: 175-80
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Stein PD, Alpert JS, Copeland J, Dalen JE, Goldman S, Turpie AG G. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 1992; 102 (04) 445S-55S
    CrossrefPubMedSearch in Google Scholar
  • 26 Hooshang T, Capitanio MA. Tracheobronchial calcification: An observation in three children after mitral valve replacement and warfarin sodium therapy. Radiology 1990; 176: 728-30
    CrossrefPubMedSearch in Google Scholar