Guidelines for antithrombotic therapy in pediatric patients☆,☆☆,★,★★
Section snippets
Congenital Disorders Predisposing to Thromboembolic Disease
Common congenital prethrombotic disorders are comprised of activated protein C resistance and deficiencies of protein C, protein S, and antithrombin (previously antithrombin III).2 Less common disorders are deficiencies of plasminogen and heparin cofactor II; dysfibrinogenemia; hyperhomocysteinemia; and defects within the fibrinolytic system.3 The heterozygote forms of these disorders rarely present with a thromboembolism during childhood.4, 5 Homozygous forms of protein C and protein S
Acquired Venous Thromboembolic Events During Childhood
Thromboembolic events occur in association with serious, identifiable primary disorders in more than 95% of children compared with only 60% of adults.4 Infants younger than 1 year of age comprise the patient population at greatest risk of TEs.4 The age distribution is important because of the relative immaturity of the hemostatic system within the first year of life, which influences the response to antithrombotic agents. The single most important cause of TEs in children is the presence of a
General Information
Complications of venous TEs can be classified as immediate or long-term and apply equally to CVL- and non–CVL-related TEs. Serious immediate complications include death from extension into the heart or PE,4 the risk of bleeding from long-term anticoagulation therapy, or ruptured collateral varices.4 Repeated CVL-induced TEs also result in loss of patency in the upper venous system necessitating placement of subsequent CVLs into the lower venous system.
Pulmonary Embolism
The cardinal symptoms of PE in children are
General Information
Arterial TEs in children are usually related to catheters placed for a short term (cardiac catheterization) or on a longer term basis (umbilical arterial catheters).62 Arterial TEs also occur in organ transplantation,63, 64 coronary aneurysms, in Kawasaki disease,65 Takayasu's arteritis,66 a variety of CHD (or their treatment), and cerebral vessels. For both catheter- and non-catheter-related arterial TE, anticoagulants are frequently used prophylactically in high-risk situations.
Cardiac Catheterization
In the absence
Parameters Modulating Activities of Antithrombotic Agents in Pediatric Patients
Antithrombotic agents used in pediatric patients are SH and its derivative, LMWH, oral anticoagulants (warfarin), antiplatelet agents (aspirin and others), and thrombolytic agents (streptokinase, urokinase, and tissue plasminogen activator.
General Recommendations for Antithrombotic Therapy
The following recommendations are based on a systematic review of the literature and the Fourth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy.1 The levels of evidence and the grades of recommendations for therapy are provided in Table IV.
Level of evidence Grade of recommendation Level I
Grade A Level I Results come from a single RCT in which the lower limit of the CI for the treatment effect exceeds the minimal clinically important benefit. Level I+ Results come
The Future of Childhood Thrombophilia
The emergence of a new medical discipline in pediatrics is usually unexpected and without immediate resources or expertise within the group of health care providers. Childhood thrombophilia is clearly a new field in pediatrics and a natural component of pediatric hematology/oncology programs. The term thrombophilia was selected because it includes the use of anticoagulants in children for reasons other than the prevention or treatment of TEs (i.e., cardiopulmonary bypass, dialysis,
Summary
Because of the relatively low incidence of TEs in children, the diagnostic and therapeutic approaches used are largely extrapolated from guidelines for adults. Features that differ in children compared with adults include underlying disorders, high incidence of CVL-related DVT in the upper venous system, and response to SH, warfarin, and thrombolytic agents. There is a paucity of information on the risk/benefit ratio of the therapeutic interventions and long-term outcome. Clinical trials are
Acknowledgements
We would like to acknowedge Lu Ann Brooker for researching and editing this manuscript.
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Cited by (0)
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From the Hamilton Civic Hospitals Research Centre, Henderson General Division, Hamilton, and Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Center for Platelet Function Studies, University of Massachusetts Medical School, Worcester; and Department of Pathology, University of Vermont, College of Medicine, Burlington.
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Supported by Project 7 from the Medical Research Council of Canada's Group in Developmental Lung Biology. Dr. Andrew is a Career Investigator of the Heart and Stroke Foundation of Canada.
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Reprint requests: Maureen Andrew, MD, Hamilton Civic Hospitals Research Centre, Henderson General Division, 711 Concession St, 60 Wing, 2nd Floor, Hamilton, Ontario, L8V 1C3 Canada.
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9/19/83674