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Pediatric Thromboembolism Medication

  • Author: Scott C Howard, MD; Chief Editor: Robert J Arceci, MD, PhD  more...
Updated: Feb 18, 2015

Medication Summary

Information continues to emerge on the use of antithrombotic agents in neonates and children.[19] Unfractionated heparin (UFH) has for years been the mainstay of initial therapy for thromboembolism in adults and children. However, low-molecular-weight heparin (LMWH) has similar efficacy, is easier to administer and monitor, and has a lower risk of heparin-induced thrombocytopenia.

In the Reviparin in Childhood Venous Thromboembolism (REVIVE) trial,[24] researchers compared subcutaneous reviparin with UFH, followed by oral warfarin. The study was limited by the small number of patients but did show equivalence with respect to risk of bleeding and recurrent venous thromboembolism.

Medical therapy for venous thromboembolism in children is not evidence-based, because few randomized studies address important questions, such as duration of therapy for each type of venous thromboembolism. When one considers the subset of children with central venous catheter–associated thrombosis and cancer, clinical practice widely varies.[25]

If thrombosis or PE is not extensive, oral anticoagulation with warfarin may be started on the second or third day and continued for 3-6 months unless risk factors for recurrent thrombosis persist. Pediatric studies have not yet been performed to identify the optimal length of therapy for each type of thrombosis.

Adults with cancer should be treated with LMWH for 6-12 months because the rate of recurrent thrombosis with warfarin therapy is unacceptably high. Similarly, children with thromboembolism and cancer should be treated with LMWH rather than warfarin because safe therapeutic levels of anticoagulation with warfarin can rarely be achieved in children undergoing cancer therapy, and the risk of bleeding and recurrent thrombosis are therefore unacceptably high.

Patients with thrombosis associated with a central venous catheter should receive anticoagulation therapy for 3-6 months if the catheter is removed and thrombotic risk factors have resolved. However, if the central line must remain in place once the period of anticoagulation has been completed, some advocate administration of prophylactic doses of LMWH (eg, enoxaparin at 0.5 mg/kg/day) until the central venous catheter is removed.[19]

Values from the chapter “Antithrombotic and Thrombolytic Therapy,” in American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed, 2008), were used in the medication subsections below.[26]


Anticoagulants, Hematologic

Class Summary

Inhibition of thrombin prevents the formation and/or extension of thrombus and thus allows for recanalization of the blood vessel over time.

Oral anticoagulants are used to prevent recurrent or ongoing thromboembolism-related occlusion. They are the mainstays of long-term outpatient therapy in patients who do not have cancer. Oral anticoagulants competitively interfere with vitamin K metabolism, decreasing plasma concentrations of the active forms of factors II, VII, IX, and X. Compared with adults, infants and children tend to require high maintenance doses and frequent dosage adjustments. Besides warfarin, acenocoumarol has also been used.

Warfarin (Coumadin)


Warfarin interferes with the hepatic synthesis of vitamin K-dependent coagulation factors. It is used for the prophylaxis and treatment of venous thromboembolism, PE, and embolic complications. The drug is used for long-term anticoagulation.

Warfarin has a half-life of 36-42 hours. PT and INR can be difficult to monitor in children because of variability in dietary vitamin K intake, effects of other drugs, and age.

Unfractionated heparin sodium


Unfractionated heparin (UFH) sodium augments the activity of antithrombin III and prevents conversion of fibrinogen to fibrin. It does not actively lyse clots but it can inhibit further thrombogenesis. UFH prevents reaccumulation of clot after spontaneous fibrinolysis. This agent is usually started as the initial treatment for thromboembolism.

Monitor the patient's CBC count, PT, and aPTT daily after aPTT is therapeutic. For reversal, stopping infusion usually sufficient. If rapid reversal is needed, give protamine. The dose is based on the heparin received in previous 2 hours. If less than 30 minutes have passed since last dose of heparin, give 1 mg per 100 U of heparin received, not to exceed 50 mg, administered intravenously, over 10 minutes.

Enoxaparin (Lovenox)


Enoxaparin enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. It also preferentially increases the inhibition of factor Xa.

The goal is to maintain an anti-Xa level of 0.5-1 U/mL (measured peak level 4 h postinjection). Enoxaparin may be used like UFH for 5-7 days, until oral anticoagulation yields an INR of greater than 2. As an alternative, LMWH may be continued for the entire 3-6 months of treatment.

For reversal, stopping the drug usually sufficient. If rapid reversal is needed, administer protamine. If less than 3-4 hours have passed since the last dose of LMWH, give 1 mg per 1 mg (or 100 U) of LMWH received, not to exceed 50 mg, administered intravenously, over 10 minutes.

Potential advantages to enoxaparin use include less osteoporosis, equivalent or less bleeding, and less heparin-induced thrombocytopenia. Enoxaparin is useful in infants and children with poor venous access.



Class Summary

Thrombolytic agents convert plasminogen to plasmin, leading to clot lysis. Pediatric indications are not established. Because of developmental differences in the hemostatic system, infants require doses higher than those used in adults to generate the same amount of plasmin.

Thrombolytic agents are most frequently used to manage blocked central catheters and are less often used to treat PE and stroke.

Alteplase (Activase)


Alteplase is a recombinant tissue plasminogen activator (rt-PA). It is the drug of choice for thrombolysis, given that urokinase is unavailable in the United States. Alteplase is a specific, fibrin-bound plasminogen activator. Pediatric data on this drug is limited.

However, in research using a small number of infants and neonates with large-vessel thromboses, dosages were 0.01-0.5 mg/kg/h intravenous. Intracranial hemorrhage has been observed at dosages of 0.4 mg/kg or higher.


Antiplatelet Agents, Cardiovascular

Class Summary

Antiplatelet agents are used as prophylaxis for arterial thrombosis (stroke) and after Blalock-Taussig or endovascular shunt placement. They have no role in the prevention or treatment of venous thrombosis.

Aspirin (Ascriptin, Bayer Aspirin, Bufferin, Ecotrin)


Aspirin can be used in low doses to inhibit platelet aggregation and to treat the complications of venous stases and thrombosis. It irreversibly inactivates cyclo-oxygenase and ultimately prevents thromboxane A2 production in platelets. Platelet function does not fully recover until new platelets are made in 7-10 days.


Blood Components

Class Summary

Protein C concentrate is now available for replacement therapy and to treat and prevent severe sequelae caused by hereditary protein C deficiency.

Protein C concentrate, human (Ceprotin)


This agent is an orphan drug that is indicated for the prevention and treatment of life-threatening venous thromboembolism and purpura fulminans caused by severe congenital protein C deficiency. It is also indicated as replacement therapy for inherited protein C deficiency.

Protein C is an essential component of hemostasis. Thrombomodulin is necessary to convert protein C to its activated form.

The dosage and duration of protein C therapy depend on the severity of the patient's protein C deficiency and are adjusted to an individual pharmacokinetic profile.

Contributor Information and Disclosures

Scott C Howard, MD Founder and CEO, Resonance, LLC; Consultant in Oncology, Healthcare Informatics, Global Health, Research; Adjunct Professor, University of Memphis School of Health Studies

Scott C Howard, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Central American Pediatric Hematology-Oncology Association, Columbian Pediatric Hematology/Oncology Society, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD Director, Children’s Center for Cancer and Blood Disorders, Department of Hematology/Oncology, Co-Director of the Ron Matricaria Institute of Molecular Medicine, Phoenix Children’s Hospital; Editor-in-Chief, Pediatric Blood and Cancer; Professor, Department of Child Health, University of Arizona College of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.


James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Philip M Monteleone, MD Associate Professor, Department of Pediatrics, Division of Oncology, University of Pennsylvania and Children's Hospital of Philadelphi

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Virchow triad for the pathophysiology of thrombus formation.
Coagulation cascade. Solid arrows represent activation events, dashed arrows represent inhibition events, and dotted lines with circles represent inactivation events. a = active; APC = activated protein C; F = factor; FDP= fibrin degradation products; HMW = high molecular weight; PAI-1 = plasminogen activator inhibitor-1; PL = phospholipid; TM = thrombomodulin; t-PA = tissue type plasminogen activator; u-PA = urokinase plasminogen activator; XL= crosslinked.
Nomogram for adjusting the dosage of heparin. Reproduced with permission from Michelson et al (1998). APTT = activated partial thromboplastin time.
Dosing of low-molecular-weight heparins (LMWHs) in children. Reproduced with permission from Michelson et al (1998).
Warfarin dosing in children. INR = international normalized ratio. Reproduced with permission from Michelson et al (1998).
The pathophysiology of pulmonary embolism. Although pulmonary embolism can arise from anywhere in the body, most commonly it arises from the calf veins. The venous thrombi predominately originate in venous valve pockets (inset) and at other sites of presumed venous stasis. To reach the lungs, thromboemboli travel through the right side of the heart. RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.
Axial CT scan of thorax shows an embolus in the distal left pulmonary artery with an associated pleural effusion.
Thrombosis and thrombophilia.
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