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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.

Electrocardiography

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.

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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.

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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.

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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.

References
  1. Askegard-Giesmann JR, O'Brien SH, Wang W, Kenney BD. Increased use of enoxaparin in pediatric trauma patients. J Pediatr Surg. 2012 May. 47(5):980-3. [Medline].

  2. Nuss R, Hays T, Chudgar U, et al. Antiphospholipid antibodies and coagulation regulatory protein abnormalities in children with pulmonary emboli. J Pediatr Hematol Oncol. 1997 May-Jun. 19(3):202-7. [Medline].

  3. Goldenberg NA, Bernard TJ. Venous thromboembolism in children. Pediatr Clin North Am. 2008 Apr. 55(2):305-22, vii. [Medline].

  4. Sandoval JA, Sheehan MP, Stonerock CE, Shafique S, Rescorla FJ, Dalsing MC. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg. 2008 Apr. 47(4):837-43. [Medline].

  5. Gruenwald CE, Manlhiot C, Abadilla AA, Kwok J, Maxwell S, Holtby HM, et al. Heparin brand is associated with postsurgical outcomes in children undergoing cardiac surgery. Ann Thorac Surg. 2012 Mar. 93(3):878-82. [Medline].

  6. Kosch A, Koch HG, Heinecke A, et al. Increased fasting total homocysteine plasma levels as a risk factor for thromboembolism in children. Thromb Haemost. 2004. 91(2):308-14. [Medline].

  7. Altinisik J, Ates O, Ulutin T, et al. Factor V Leiden, prothrombin G20210A, and protein C mutation frequency in Turkish venous thrombosis patients. Clin Appl Thromb Hemost. 2008 Oct. 14(4):415-20. [Medline].

  8. Yamamura K, Joo K, Ohga S, Nagata H, Ikeda K, Muneuchi J, et al. Thrombocytosis in asplenia syndrome with congenital heart disease: A previously unrecognized risk factor for thromboembolism. Int J Cardiol. 2012 Jun 22. [Medline].

  9. Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr. 2004. 145(4):563-5. [Medline].

  10. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics. 2009 Oct. 124(4):1001-8. [Medline]. [Full Text].

  11. Nowak-Gottl U, Kosch A. Factor VIII, D-Dimer, and thromboembolism in children. N Engl J Med. 2004 Sep 9. 351(11):1051-3. [Medline].

  12. Goldenberg NA, Knapp-Clevenger R, Manco-Johnson MJ. Elevated plasma factor VIII and D-dimer levels as predictors of poor outcomes of thrombosis in children. N Engl J Med. 2004 Sep 9. 351(11):1081-8. [Medline].

  13. Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994 Mar 1. 83(5):1251-7. [Medline].

  14. Monagle P, Adams M, Mahoney M, et al. Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry. Pediatr Res. 2000 Jun. 47(6):763-6. [Medline].

  15. Kuhle S, Koloshuk B, Marzinotto V, et al. A cross-sectional study evaluating post-thrombotic syndrome in children. Thromb Res. 2003. 111(4-5):227-33. [Medline].

  16. Athale U, Siciliano S, Thabane L, Pai N, Cox S, Lathia A. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer. 2008 Dec. 51(6):792-7. [Medline].

  17. Athale UH, Nagel K, Khan AA, Chan AK. Thromboembolism in children with lymphoma. Thromb Res. 2008. 122(4):459-65. [Medline].

  18. Biss TT, Brandao LR, Kahr WH, Chan AK, Williams S. Clinical features and outcome of pulmonary embolism in children. Br J Haematol. 2008 Sep. 142(5):808-18. [Medline].

  19. Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb. 141(2 Suppl):e737S-801S. [Medline]. [Full Text].

  20. Lidegaard O, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ. 2011 Oct 25. 343:d6423. [Medline]. [Full Text].

  21. Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood. 2007 Mar 15. 109(6):2419-23. [Medline].

  22. Aissaoui N, Martins E, Mouly S, Weber S, Meune C. A meta-analysis of bed rest versus early ambulation in the management of pulmonary embolism, deep vein thrombosis, or both. Int J Cardiol. 2009 Sep 11. 137(1):37-41. [Medline].

  23. Anderson CM, Overend TJ, Godwin J, Sealy C, Sunderji A. Ambulation after deep vein thrombosis: a systematic review. Physiother Can. 2009 Summer. 61(3):133-40. [Medline]. [Full Text].

  24. Massicotte P, Julian JA, Gent M, et al. An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial. Thromb Res. 2003. 109(2-3):85-92. [Medline].

  25. Skinner R, Koller K, McIntosh N, McCarthy A, Pizer B. Prevention and management of central venous catheter occlusion and thrombosis in children with cancer. Pediatr Blood Cancer. 2008 Apr. 50(4):826-30. [Medline].

  26. Monagle P, Chalmers E, Chan A, et al. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun. 133(6 Suppl):887S-968S. [Medline].

  27. Agnelli G, Verso M. Epidemiology of cerebral vein and sinus thrombosis. Front Neurol Neurosci. 2008. 23:16-22. [Medline].

  28. Aissaoui N, Martins E, Mouly S, et al. A meta-analysis of bed rest versus early ambulation in the management of pulmonary embolism, deep vein thrombosis, or both. Int J Cardiol. 2008 Aug 6. [Medline].

  29. Akl EA, Rohilla S, Barba M, et al. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer: a systematic review. Cancer. 2008 Oct 1. 113(7):1685-94. [Medline].

  30. Alioglu B, Avci Z, Tokel K, et al. Thrombosis in children with cardiac pathology: analysis of acquired and inherited risk factors. Blood Coagul Fibrinolysis. 2008 Jun. 19(4):294-304. [Medline].

  31. Athale U, Siciliano S, Thabane L, et al. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer. 2008 Dec. 51(6):792-7. [Medline].

  32. Babyn PS, Gahunia HK, Massicotte P. Pulmonary thromboembolism in children. Pediatr Radiol. 2005 Mar. 35(3):258-74. [Medline].

  33. Barnes C, Newall F, Ignjatovic V, et al. Reduced bone density in children on long-term warfarin. Pediatr Res. 2005. 57(4):578-81. [Medline].

  34. Billett HH. Antiplatelet agents and arterial thrombosis. Cardiol Clin. 2008 May. 26(2):189-201, vi. [Medline].

  35. Dentali F, Gianni M, Agnelli G, et al. Association between inherited thrombophilic abnormalities and central venous catheter thrombosis in patients with cancer: a meta-analysis. J Thromb Haemost. 2008 Jan. 6(1):70-5. [Medline].

  36. Faustino EV, Hanson S, Spinella PC, Tucci M, O'Brien SH, Nunez AR, et al. A multinational study of thromboprophylaxis practice in critically ill children. Crit Care Med. 2014 May. 42(5):1232-40. [Medline].

  37. Gist KM, Chima RS. The landscape of thromboprophylaxis utilization in critically ill children: sparse and variable. Crit Care Med. 2014 May. 42(5):1317-8. [Medline].

  38. Goldenberg NA, Everett AD, Graham D, Bernard TJ, Nowak-Göttl U. Proteomic and other mass spectrometry based "omics" biomarker discovery and validation in pediatric venous thromboembolism and arterial ischemic stroke: Current state, unmet needs, and future directions. Proteomics Clin Appl. 2014 Dec. 8(11-12):828-36. [Medline].

  39. Journeycake JM, Manco-Johnson MJ. Thrombosis during infancy and childhood: what we know and what we do not know. Hematol Oncol Clin North Am. 2004. 18(6):1315-38, viii-ix. [Medline].

  40. Male C, Chait P, Ginsberg JS, et al. Comparison of venography and ultrasound for the diagnosis of asymptomatic deep vein thrombosis in the upper body in children: results of the PARKAA study. Prophylactic Antithrombin Replacement in Kids with ALL treated with Asparaginase. Thromb Haemost. 2002. 87(4):593-8. [Medline].

  41. Morgan J. Perioperative venous thrombosis in children: is it time for primary prophylaxis?. Paediatr Anaesth. 2007 Feb. 17(2):99-101. [Medline].

  42. Price VE, Chan AK. Arterial thrombosis in children. Expert Rev Cardiovasc Ther. 2008 Mar. 6(3):419-28. [Medline].

  43. Price VE, Chan AK. Venous thrombosis in children. Expert Rev Cardiovasc Ther. 2008 Mar. 6(3):411-8. [Medline].

  44. Streif W, Andrew M, Marzinotto V, et al. Analysis of warfarin therapy in pediatric patients: a prospective cohort study of 319 patients. Blood. 1999. 94(9):3007-14. [Medline].

  45. van Beynum IM, Smeitink JA, den Heijer M, et al. Hyperhomocysteinemia: a risk factor for ischemic stroke in children. Circulation. 1999 Apr 27. 99(16):2070-2. [Medline].

  46. Vidal E, Sharathkumar A, Glover J, Faustino EV. Central venous catheter-related thrombosis and thromboprophylaxis in children:a systematic review and meta-analysis. J Thromb Haemost. 2014 May 6. [Medline].

  47. Vu LT, Nobuhara KK, Lee H, et al. Determination of risk factors for deep venous thrombosis in hospitalized children. J Pediatr Surg. 2008 Jun. 43(6):1095-9. [Medline].

  48. Wasay M, Dai AI, Ansari M, et al. Cerebral venous sinus thrombosis in children: a multicenter cohort from the United States. J Child Neurol. 2008 Jan. 23(1):26-31. [Medline].

  49. Young G, Albisetti M, Bonduel M, et al. Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies. Circulation. 2008 Sep 23. 118(13):1373-82. [Medline].

  50. Young G, Manco-Johnson M, Gill JC, et al. Clinical manifestations of the prothrombin G20210A mutation in children: a pediatric coagulation consortium study. J Thromb Haemost. 2003 May. 1(5):958-62. [Medline].

 
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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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