eMedicine Specialties > Pediatrics: General Medicine > Hematology

Thromboembolism: Differential Diagnoses & Workup

Author: Scott C Howard, MD, Associate Professor, University of Tennessee College of Medicine; Associate Member, Department of Oncology, Director of Clinical Trials, International Outreach Program, St Jude Children's Research Hospital
Coauthor(s): Philip M Monteleone, MD, Associate Professor, Department of Pediatrics, Division of Oncology, University of Pennsylvania and Children's Hospital of Philadelphia
Contributor Information and Disclosures

Updated: Jan 13, 2009

Differential Diagnoses

Acute Lymphoblastic Leukemia
Head Trauma
Acute Myelocytic Leukemia
Meningitis, Bacterial
Antiphospholipid Antibody Syndrome
Nephrotic Syndrome
Atrial Fibrillation
Pneumonia
Baker Cyst
Sepsis
Cardiomyopathy, Hypertrophic
Vasculitis and Thrombophlebitis
Consumption Coagulopathy

Other Problems to Be Considered

Trauma
Congenital heart disease
Neoplasm of the CNS

Workup

Laboratory Studies

No specific laboratory tests are available to diagnose a 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.

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

  • CBC count with peripheral blood smears: Anemia, thrombocytopenia, and/or 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 deep venous thrombosis (DVT) and/or pulmonary embolism (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 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 sonography is increasingly 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 recent years, CT scanning or magnetic resonance angiography (MRA) have largely replaced V/Q scanning in children.

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

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 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 for detecting early arterial ischemic stroke because CT findings are often normal.

Chest radiography

Chest radiography is most 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.

Other Tests

ECG 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.

More on Thromboembolism

Overview: Thromboembolism
Differential Diagnoses & Workup: Thromboembolism
Treatment & Medication: Thromboembolism
Follow-up: Thromboembolism
Multimedia: Thromboembolism
References
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References

  1. 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].

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

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

  4. 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. Sep 9 2004;351(11):1081-8. [Medline].

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

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

  7. 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. Apr 2008;47(4):837-43. [Medline].

  8. 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].

  9. 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. Oct 2008;14(4):415-20. [Medline].

  10. 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. Dec 2008;51(6):792-7. [Medline].

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

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

  13. 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. Jun 2008;133(6 Suppl):887S-968S. [Medline].

  14. 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].

  15. 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. Apr 2008;50(4):826-30. [Medline].

  16. 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. Jun 2008;133(6 Suppl):887S-968S. [Medline].

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

  18. 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. Aug 6 2008;[Medline].

  19. Akar N, Akar E, Deda G, et al. Coexistence of two prothrombotic mutations, factor V 1691 G-A and prothrombin gene 20210 G-A, and the risk of cerebral infarct in pediatric patients. Pediatr Hematol Oncol. Nov-Dec 1999;16(6):565-6. [Medline].

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

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

  22. Andrew M. Developmental hemostasis: relevance to hemostatic problems during childhood. Semin Thromb Hemost. 1995;21(4):341-56. [Medline].

  23. Andrew M, David M, deVeber G, et al. Arterial thromboembolic complications in paediatric patients. Thromb Haemost. Jul 1997;78(1):715-25. [Medline].

  24. Andrew M, deVeber G. Low molecular weight heparin. In: Pediatric Thromboembolism and Stroke Protocols. Hamilton, Ontario: BC Decker; 1997:6-10.

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

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

  27. 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].

  28. Bick RL. Therapy for venous thrombosis: guidelines for a competent and cost-effective approach. Clin Appl Thromb Hemost. Jan 1999;5(1):2-9. [Medline].

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

  30. 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. Jan 2008;6(1):70-5. [Medline].

  31. deVeber G, Monagle P, Chan A, et al. Prothrombotic disorders in infants and children with cerebral thromboembolism. Arch Neurol. Dec 1998;55(12):1539-43. [Medline].

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

  33. Hagstrom JN, Walter J, Bluebond-Langner R, et al. Prevalence of the factor V leiden mutation in children and neonates with thromboembolic disease. J Pediatr. Dec 1998;133(6):777-81. [Medline].

  34. Helmerhorst FM, Bloemenkamp KW, Rosendaal FR. Oral contraceptives and thrombotic disease: risk of venous thromboembolism. Thromb Haemost. Jul 1997;78(1):327-33. [Medline].

  35. Ignjatovic V, Barnes C, Newall F, et al. Point of care monitoring of oral anticoagulant therapy in children: comparison of CoaguChek Plus and Thrombotest methods with venous international normalised ratio. Thromb Haemost. Oct 2004;92(4):734-7. [Medline].

  36. 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].

  37. 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].

  38. 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].

  39. Male C, Lechner K, Eichinger S, et al. Clinical significance of lupus anticoagulants in children. J Pediatr. Feb 1999;134(2):199-205. [Medline].

  40. Manco-Johnson MJ. Disorders of hemostasis in childhood: risk factors for venous thromboembolism. Thromb Haemost. Jul 1997;78(1):710-4. [Medline].

  41. Michelson AD, Bovill E, Monagle P, Andrew M. Antithrombotic therapy in children. Chest. Nov 1998;114(5 Suppl):748S-769S. [Medline].

  42. Monagle P, Michelson AD, Bovill E, Andrew M. Antithrombotic therapy in children. Chest. Jan 2001;119(1 Suppl):344S-370S. [Medline].

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

  44. Nowak-Gottl U, Schobess R, Kurnik K, et al. Elevated lipoprotein(a) concentration is an independent risk factor of venous thromboembolism. Blood. May 1 2002;99(9):3476-7; author reply 3477-8. [Medline].

  45. Nowak-Gottl U, von Kries R, Gobel U. Neonatal symptomatic thromboembolism in Germany: two year survey. Arch Dis Child Fetal Neonatal Ed. May 1997;76(3):F163-7. [Medline].

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

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

  48. Rivkin MJ, Volpe JJ. Strokes in children. Pediatr Rev. Aug 1996;17(8):265-78. [Medline].

  49. Sifontes MT, Nuss R, Hunger SP, et al. Activated protein C resistance and the factor V Leiden mutation in children with thrombosis. Am J Hematol. 1998;57(1):29-32. [Medline].

  50. 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].

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

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

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

  54. [Best Evidence] 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. Sep 23 2008;118(13):1373-82. [Medline].

  55. 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. May 2003;1(5):958-62. [Medline].

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Further Reading

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Keywords

thrombosis, clots, thrombus, embolism, thrombus embolism, TE, thrombi, blood clot, venous thromboembolism, VTE, deep venous thrombosis, deep vein thrombosis, DVT, pulmonary embolism, PE, postthrombotic syndrome, post-thrombotic syndrome, PTS, central venous catheter, CVC, stasis, CNS thrombosis, renal vein thrombosis, antiphospholipid antibody syndrome, APLA, stroke, obesity, nephrotic syndrome, systemic lupus erythematosus, acute lymphoblastic leukemia

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Contributor Information and Disclosures

Author

Scott C Howard, MD, Associate Professor, University of Tennessee College of Medicine; Associate Member, Department of Oncology, Director of Clinical Trials, International Outreach Program, St Jude Children's Research Hospital
Scott C Howard, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Coauthor(s)

Philip M Monteleone, MD, Associate Professor, Department of Pediatrics, Division of Oncology, University of Pennsylvania and Children's Hospital of Philadelphia
Philip M Monteleone, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

J Martin Johnston, MD, Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital
J Martin Johnston, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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; 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.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Department of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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