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Pediatric Thromboembolism Treatment & Management

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

Approach Considerations

Initial care and evaluation for thromboembolism should occur in a pediatric inpatient ward or the ICU if severe respiratory distress or neurologic deterioration occurs. Management includes assessment of the extent of the thrombosis and clinical consequences, a search for thrombophilic risk factors, and anticoagulation therapy.

The duration of anticoagulation depends on the extent and location of the thrombosis, whether the thrombophilic risk factors have resolved, and, in some cases, the degree of thrombotic resolution after the initial therapy.[3, 4, 16, 17, 18, 19]

Neonatal care

Developmental differences in the hemostatic systems of newborns create difficulties in the management of thromboembolism. In addition, neonates have low levels of antithrombin and plasminogen, which cause relative resistance to heparin and thrombolytic agents, respectively.

Moreover, newborns need 11 times the usual concentration of urokinase given to adults and 5 times the usual concentration of tissue plasminogen activator (t-PA) in order to achieve the same rate of plasminogen activation.

Thrombectomy

On occasion, surgical thrombectomy may be necessary, especially after major cardiac surgery or if thrombolytic agents fail or are contraindicated.

Consultations

A pediatric hematologist should be involved in the care of all neonates, infants, and children with thromboembolism, and a pediatric neurologist should be involved in the care of children with suspected or proven CNS thrombosis.

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Inpatient Care

Admit patients with thromboembolisms to a pediatric or adolescent ward or ICU, depending on their respiratory and neurologic status.

Anticoagulation is begun with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), followed by oral anticoagulation with warfarin. Children require daily follow-up until their international normalized ratio (INR) is more than 2 on 2 successive days. Monitor the patient's INR more closely than usual if changes occur in the patient’s medications or diet.

Obtain daily CBC, prothrombin time (PT), and activated partial thromboplastin time (aPTT) values while children are inpatients. If LMWH is used, obtain an anti–activated factor X (anti-Xa) level and adjust the dose to achieve a level of 0.5-1 U/mL.

A patient's medication may include heparin or LMWH, oral anticoagulants, thrombolytic agents, and, occasionally, antiplatelet agents (for arterial thrombosis). Avoid giving antiplatelet agents to children receiving anticoagulation unless they are absolutely necessary.

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Duration of Therapy

The duration of therapy depends on the underlying problem. Children with mechanical heart valves or recurrent thromboembolism require anticoagulation indefinitely. Children with thromboembolism and persistent risk factors may be treated for 3 months and then switched to low-dose warfarin until the risk factor is no longer present. Uncomplicated DVT can be treated for 3-6 months.

Monitor children who are taking LMWH for more than 4 weeks; obtain a CBC count every 1-4 weeks to look for heparin-induced thrombocytopenia and an anti–activated factor X level (every 2-6 wk once a therapeutic level is achieved). Enoxaparin may accumulate over time, and dosage adjustments may be necessary.

After discontinuation of anticoagulation, reducing subsequent risk factors for thrombosis is an important component of lifelong management. For example, patients with a history of thrombosis should avoid smoking and the use of oral contraceptives that include estrogens (desogestrel, gestodene, or drospirenone).[20]

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Diet

Vitamin K directly interferes with the effectiveness of warfarin and potentially increases the risk for recurrent thrombosis. Daily intake of foods high in vitamin K, such as green, leafy vegetables, should be kept at a consistent level. For example, patients should eat similar amounts of vitamin-K rich foods each day. The patient or family should inform the physician of any changes in the patient’s diet or medications.

Maternal intake of vitamin K can affect levels in breast milk and cause problems in neonates and infants that are similar to those in other patients who consume vitamin K in food. Supplementation with a consistent amount of formula per day has been recommended. Formula-fed infants should receive formula with the lowest concentration of vitamin K available.

Vitamin K should be removed from parenteral nutrition or a constant, small amount should be used each day. Because regulation of dietary vitamin K intake is very difficult, one study found that daily administration of 1 mg of vitamin K plus a somewhat higher dose of warfarin led to more stable INR values in patients receiving long-term anticoagulation.[21]

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Activity

Children with thromboembolism are sometimes restricted to bed rest for the first 24-48 hours to decrease the risk of PE. However, this practice has never been shown to reduce the risk of embolization, and adults treated for DVT as outpatients (without bed rest) have been found to have no higher incidence of PE than those treated as inpatients. Children with lower-extremity DVT should be fitted for compression stockings to reduce the risk of postthrombotic syndrome.[22, 23]

Patients should avoid participating in contact sports while they are receiving anticoagulation.

Sexually active female adolescents should use some form of birth control, preferably not oral contraceptives, if they are receiving oral anticoagulants. Warfarin is teratogenic, so women on chronic warfarin therapy must not become pregnant.

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Monitoring

For patients receiving oral anticoagulation, monitor the PT and/or INR within 3 days of their discharge from the hospital. Always check the INR 5-7 days after adjusting the dose. After the INR is 2-3 (or 2.5-3.5 in patients with mechanical heart valves) on 2 successive measurements obtained 1 week apart, the monitoring interval can be lengthened to every 2 weeks. In general, the INR is monitored monthly. Children taking warfarin for more than a year should be monitored for decreased bone density.

Point-of-care monitoring of oral anticoagulation may be available for home use or at specialized pediatric anticoagulation clinics. Point-of-care monitoring is especially helpful for children who require indefinite oral anticoagulation as part of treatment for congenital heart disease or inherited hypercoagulable disorders.

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Contributor Information and Disclosures
Author

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.

Acknowledgements

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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