Chest
Volume 108, Issue 4, Supplement, October 1995, Pages 506S-522S
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Antithrombotic Therapy in Children

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MECHANISM OF ACTION OF HEPARIN: AGE-DEPENDENT FEATURES

Heparin's anticoagulant activities, which are mediated by catalysis of antithrombin III (ATIII), can be impaired in the presence of decreased plasma levels of ATIII. Some pediatric patients requiring heparin therapy have very low levels of ATIII reflecting physiologic, congenital, and/or acquired etiologies. For example, plasma concentrations of ATIII are physiologically low at birth (approximately 0.50 U/mL) and increase to adult values by 3 months of age.3, 4, 5 Sick premature newborns, a

Age-Dependent Features

Oral anticoagulants function by reducing plasma concentrations of the vitamin K-dependent proteins. At birth, levels of the vitamin K-dependent coagulant factors (FII, FVII, FIX, FX) and inhibitors (protein C, protein S) are approximately 50% of adult values.3, 4, 5,26, 27, 28 These levels are similar to those found in adults receiving oral anticoagulants for the treatment of venous thrombotic disease.9 A small number of newborns have evidence of a functional vitamin K deficiency state,

Age-Dependent Features

Compared with adult controls, neonatal platelets are hyporeactive to thrombin, adenosine diphosphate/epinephrine, and thromboxane A2.62 This hyporeactivity of neonatal platelets is the result of a defect intrinsic to neonatal platelets.62 Paradoxically, the bleeding time is short in newborns owing to increased RBC size, high hematocrit, and increased levels and multimeric forms of von Willebrand factor.63, 64, 65 No studies of platelet function in healthy children were identified except for the

MECHANISM OF ACTION OF THROMBOLYTIC AGENTS: AGE-DEPENDENT FEATURES

The actions of thrombolytic agents are mediated by converting endogenous plasminogen to plasmin. At birth, plasma concentrations of plasminogen are reduced to 50% of adult values (21 mg/100 mL).3,4,85 The decreased levels of plasminogen in newborns slow the generation of plasmin87 and reduce the thrombolytic effects of streptokinase (SK), urokinase (UK), and tissue plasminogen activator (tPA) in an in vitro fibrin clot system.88,89 A similar response occurs in children with acquired plasminogen

Treatment of Bleeding Due to Thrombolytic Therapy

Before thrombolytic therapy is used, it is advisable, when possible, to correct other concurrent hemostatic problems such as thrombocytopenia or vitamin K deficiency. Clinically mild bleeding, which is usually oozing from a wound or puncture site, can be treated with local pressure and supportive care. Major bleeding from a local site can be treated by stopping the infusion of thrombolytic agent and administering cryoprecipitate (usual dose of one bag per 5 kg) and other blood products as

INDICATIONS FOR ANTITHROMBOTIC THERAPY IN PEDIATRIC PATIENTS

Although the general indications for antithrombotic therapy in pediatric patients are similar to adults, the frequency of specific disease states and underlying abnormalities differ. For example, myocardial infarction and cerebrovascular accidents (CVAs) are two of the more common indications for antithrombotic therapy in adults and are the least common in children.40 The current indications for antithrombotic therapy in children are provided in Table 7.

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