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Pediatric Thromboembolism Workup

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

Approach Considerations

No specific laboratory tests are available to diagnose thromboembolism. However, D-dimer levels may be useful, especially for ruling out thrombosis, because a normal value rarely occurs when significant thrombosis is present.

Many clotting factors are consumed in a clot, and a low factor level may be an effect rather than a cause of thrombosis; therefore, most clotting factors should be evaluated 1-2 months after successful treatment of the clot.

Neonatal thrombosis

Neonates have multiple risk factors for thromboembolism, including prematurity, sepsis, and frequent use of central arterial and venous lines.


Electrocardiographic findings are usually normal or show only sinus tachycardia. In children, the classic findings of T-wave inversion in the right precordial leads, right-axis deviation, and an incomplete or complete bundle branch block are rarely present after PE.


Laboratory Studies

Once a clot is documented, the patient's workup should include the following:

  • Complete blood count (CBC) with peripheral blood smears - Anemia, thrombocytopenia, and/or red blood cell (RBC) fragments may suggest disseminated intravascular coagulation; document a normal platelet count before heparin or low-molecular-weight heparin (LMWH) is started
  • Measurement of the prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level - A prolonged PT or aPTT and/or a low fibrinogen level may suggest disseminated intravascular coagulation; a prolonged aPTT at baseline may be due to the use of an inhibitor or lupus anticoagulant
  • D-dimer measurement - Data from several studies of adults suggest that the D-dimer level may be useful in ruling out DVT and/or PE, in conjunction with careful assessment of the clinical probability; of note, children often have other systemic disorders, such as sepsis or malignancy, which may elevate D-dimer concentrations

First-line workup for hypercoagulation

This workup should include evaluations of the following:

  • Activated protein C resistance and/or the factor V Leiden mutation
  • Protein C
  • Free and total protein S
  • Antithrombin
  • Lupus anticoagulant (which may be screened by using the dilute Russell viper venom test)
  • Anticardiolipin antibodies
  • Prothrombin gene 20210A mutation
  • Lipoprotein(a) levels
  • Plasma homocysteine values (which can be measured after fasting or at 4 h after a loading dose of methionine 100 mg/kg)

After heparin or LMWH therapy is begun, remember that it affects antithrombin, as well as protein C, protein S, and activated protein C resistance. Warfarin also affects protein C, protein S, and antithrombin. Neither drug affects anticardiolipin antibodies, factor V Leiden, the prothrombin mutation, lipoprotein(a), or homocysteine levels.


Imaging Studies

Contrast venography

Contrast venography is considered the reference standard for documenting DVT in children. Venograms are reliable in any portion of the venous system except the jugular veins. Limitations of this study include difficulty in cannulating small veins in children and the occasional patient with an allergy to the contrast medium.

Duplex ultrasonography or real-time B-mode ultrasonography with color Doppler imaging

In adults, duplex ultrasonography compares favorably with contrast venography, especially for diagnosing DVT of the lower extremities. Duplex ultrasonography is increasingly being used as the primary diagnostic tool to confirm thrombosis in adults and children.

No randomized trials in children have been performed to validate its usefulness. However, one study of children with acute lymphoblastic leukemia demonstrated that ultrasonography was insensitive for DVT in the superior vena cava, subclavian veins, or brachiocephalic veins.

In vessels with thrombosis, Doppler signals are absent, and the lumen cannot be compressed with direct pressure.

Ventilation-perfusion scanning

Ventilation-perfusion (V/Q) scanning used to be the procedure of choice in children with suspected PE. A high-probability scan is one that shows a peripherally based perfusion defect with normal ventilation (mismatch). In adults, a high probability scan with high clinical suspicion is correctly predictive of PE 96% of the time. A difficult situation may occur when the scan is interpreted as suggesting an intermediate probability for PE; for adults with this finding, PE is ultimately proven in 33%.

In children, V/Q scanning has largely been replaced by computed tomography (CT) scanning or magnetic resonance angiography (MRA).

As an alternative, the D-dimer test may be used to help screen for clinically significant clots, as suggested by data from studies in adults. If the D-dimer level is elevated and if CT scanning or MRA reveal a defect in the vessel, a diagnosis of PE is confirmed.

MRI and MRA of the head

Magnetic resonance imaging (MRI) and MRA of the head are the modalities of choice for evaluating a child with suspected CNS thrombosis. Diffusion-weighted MRI is highly sensitive for detecting acute strokes in adults.

Head CT scanning with intravenous contrast enhancement

Head CT scanning performed with intravenous contrast material is sometimes useful for detecting sinovenous thrombosis. MRI and MRA are better than CT scanning for detecting early arterial ischemic stroke because CT findings are often normal.

Chest radiography

Chest radiography is more helpful for suggesting alternative diagnoses, such as pneumonia, than for diagnosing thromboembolism. Radiographic findings are most often normal in patients with PE, although a small pleural effusion with a wedge-shaped, pleural-based opacity of pulmonary infarction may be seen in some cases. In children, pneumonia is far more common than thromboembolism.

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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