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Semin Thromb Hemost 2011; 37(7): 772-785
DOI: 10.1055/s-0031-1297168
© Thieme Medical Publishers

Pulmonary Embolism in Children

Leonardo R. Brandão1 , Veerle Labarque1 , Yaser Diab1 , Suzan Williams1 , David E. Manson2
  • 1Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
  • 2Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada
Further Information

Publication History

Publication Date:
20 December 2011 (online)

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ABSTRACT

Pulmonary embolism (PE) has long been described in children. Nevertheless, most of the algorithms applied to patients within this age range, from diagnosis to therapy, have been adapted from adult protocols. This article reviews the progresses that occurred to PE in children placing them in historical perspective with the key events relevant to PE in adults. A brief summary of the initial reports encountered in the pediatric literature followed by key conclusions drawn from national database reports characterizing its epidemiology in children is highlighted. Additionally, a section with the diagnostic tools pertaining to children is included. Closing remarks encompass commentaries related to therapy and outcomes, reflecting on current knowledge gaps related to PE in children.

KEYWORDS

Anticoagulation - children - deep vein thrombosis - pulmonary embolism - pulmonary hypertension

REFERENCES

  • 1 WHO .Health statistics and health information systems. [Cited 2011 April 8]; Available from: http://www.who.int/healthinfo/en/
    Google Scholar
  • 2 Silverstein M D, Heit J A, Mohr D N, Petterson T M, O'Fallon W M, Melton III L J. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.  Arch Intern Med. 1998;  158 (6) 585-593
    Google Scholar
  • 3 Billard C. A Treatise on the Disease of Infants, Founded on Recent Clinical Observations and Investigations in Pathological Anatomy Made at the Hospice des Énfants-Trouves, with a Dissertation on the Viability of the Child. J & H Langley ed. 1839
    Google Scholar
  • 4 Löschner . Phlebitis venae cruralis sinistrae, peri- et myocarditis, embolis et oedema pulmonum.  Jahrb f Kinderh. 1861;  4 66
    Google Scholar
  • 5 Stevenson G F, Stevenson F L. Pulmonary embolism in childhood.  J Pediatr. 1949;  34 (1) 62-69
    Google Scholar
  • 6 Coon W W, Coller F A. Some epidemiologic considerations of thromboembolism.  Surg Gynecol Obstet. 1959;  109 487-501
    Google Scholar
  • 7 Buck J R, Connors R H, Coon W W, Weintraub W H, Wesley J R, Coran A G. Pulmonary embolism in children.  J Pediatr Surg. 1981;  16 (3) 385-391
    Google Scholar
  • 8 Byard R W, Cutz E. Sudden and unexpected death in infancy and childhood due to pulmonary thromboembolism. An autopsy study.  Arch Pathol Lab Med. 1990;  114 (2) 142-144
    Google Scholar
  • 9 Schein C J, Rifkin H, Hurwitt E S, Lebendiger A. The clinical and surgical aspects of chronic pulmonary artery thrombosis.  AMA Arch Intern Med. 1958;  101 (3) 592-605
    Google Scholar
  • 10 Wood K E. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism.  Chest. 2002;  121 (3) 877-905
    Google Scholar
  • 11 Elliott C G. Pulmonary physiology during pulmonary embolism.  Chest. 1992;  101 (4, Suppl) 163S-171S
    Google Scholar
  • 12 Benotti J R. Pulmonary angiography in the diagnosis of pulmonary embolism.  Herz. 1989;  14 (2) 115-125
    Google Scholar
  • 13 Kröger K, Moerchel Ch, Moysidis T, Santosa F. Incidence rate of pulmonary embolism in Germany: data from the federal statistical office.  J Thromb Thrombolysis. 2010;  29 (3) 349-353
    Google Scholar
  • 14 Jones D R, Macintyre I M. Venous thromboembolism in infancy and childhood.  Arch Dis Child. 1975;  50 (2) 153-155
    Google Scholar
  • 15 Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry.  Pediatrics. 1995;  96 (5 Pt 1) 939-943
    Google Scholar
  • 16 Nowak-Göttl U, von Kries R, Göbel U. Neonatal symptomatic thromboembolism in Germany: two year survey.  Arch Dis Child Fetal Neonatal Ed. 1997;  76 (3) F163-F167
    Google Scholar
  • 17 van Ommen C H, Heijboer H, Büller H R, Hirasing R A, Heijmans H S, Peters M. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands.  J Pediatr. 2001;  139 (5) 676-681
    Google Scholar
  • 18 Kuhle S, Massicotte P, Chan A et al.. Systemic thromboembolism in children. Data from the 1–800-NO-CLOTS Consultation Service.  Thromb Haemost. 2004;  92 (4) 722-728
    Google Scholar
  • 19 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) 1251-1257
    Google Scholar
  • 20 Gibson BES, Chalmers E A, Bolton-Maggs P, Henderson D J, Boshkov R L. Thromboembolism in childhood: a prospective 2-year study in the United Kingdom (interim: Feb 2001-Feb 2003).  J Thromb Haemost. 2003;  1 (Supp 1)
    Google Scholar
  • 21 Stein P D, Kayali F, Olson R E. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey.  J Pediatr. 2004;  145 (4) 563-565
    Google Scholar
  • 22 Biss T T, Brandão L R, Kahr W H, Chan A K, Williams S. Clinical features and outcome of pulmonary embolism in children.  Br J Haematol. 2008;  142 (5) 808-818
    Google Scholar
  • 23 Raffini L, Huang Y S, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007.  Pediatrics. 2009;  124 (4) 1001-1008
    Google Scholar
  • 24 David M, Andrew M. Venous thromboembolic complications in children.  J Pediatr. 1993;  123 (3) 337-346
    Google Scholar
  • 25 Kjellin I B, Boechat M I, Vinuela F, Westra S J, Duckwiler G R. Pulmonary emboli following therapeutic embolization of cerebral arteriovenous malformations in children.  Pediatr Radiol. 2000;  30 (4) 279-283
    Google Scholar
  • 26 Farrell A G, Parikh S R, Darragh R K, Girod D A. Retrieval of “old” foreign bodies from the cardiovascular system in children.  Cathet Cardiovasc Diagn. 1998;  44 (2) 212-216, discussion 217
    Google Scholar
  • 27 Soares F A. Fatal pulmonary tumor embolism caused by chondroblastic osteosarcoma.  Arch Pathol Lab Med. 2000;  124 (5) 661
    Google Scholar
  • 28 Victoria T, Mong A, Altes T et al.. Evaluation of pulmonary embolism in a pediatric population with high clinical suspicion.  Pediatr Radiol. 2009;  39 (1) 35-41
    Google Scholar
  • 29 Bernstein D, Coupey S, Schonberg S K. Pulmonary embolism in adolescents.  Am J Dis Child. 1986;  140 (7) 667-671
    Google Scholar
  • 30 Rajpurkar M, Warrier I, Chitlur M et al.. Pulmonary embolism-experience at a single children's hospital.  Thromb Res. 2007;  119 (6) 699-703
    Google Scholar
  • 31 Tavil B, Kuskonmaz B, Kiper N, Cetin M, Gumruk F, Gurgey A. Pulmonary thromboembolism in childhood: a single-center experience from Turkey.  Heart Lung. 2009;  38 (1) 56-65
    Google Scholar
  • 32 Wells P S, Anderson D R, Rodger M et al.. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer.  Thromb Haemost. 2000;  83 (3) 416-420
    Google Scholar
  • 33 Biss T T, Brandão L R, Kahr W H, Chan A K, Williams S. Clinical probability score and D-dimer estimation lack utility in the diagnosis of childhood pulmonary embolism.  J Thromb Haemost. 2009;  7 (10) 1633-1638
    Google Scholar
  • 34 Mcginn S, White P D. Acute cor pulmonale resulting from pulmonary embolism.  JAMA. 1935;  104 1473-1479
    Google Scholar
  • 35 Rodger M, Makropoulos D, Turek M et al.. Diagnostic value of the electrocardiogram in suspected pulmonary embolism.  Am J Cardiol. 2000;  86 (7) 807-809, A10
    Google Scholar
  • 36 The PIOPED Investigators . Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED).  JAMA. 1990;  263 (20) 2753-2759
    Google Scholar
  • 37 Worsley D F, Alavi A, Aronchick J M, Chen J T, Greenspan R H, Ravin C E. Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study.  Radiology. 1993;  189 (1) 133-136
    Google Scholar
  • 38 Novelline R A, Baltarowich O H, Athanasoulis C A, Waltman A C, Greenfield A J, McKusick K A. The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram.  Radiology. 1978;  126 (3) 561-567
    Google Scholar
  • 39 van Beek E J, Reekers J A, Batchelor D A, Brandjes D P, Büller H R. Feasibility, safety and clinical utility of angiography in patients with suspected pulmonary embolism.  Eur Radiol. 1996;  6 (4) 415-419
    Google Scholar
  • 40 van Beek E J, Brouwerst E M, Song B, Stein P D, Oudkerk M. Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism—a critical review.  Clin Radiol. 2001;  56 (10) 838-842
    Google Scholar
  • 41 Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology.  Eur Heart J. 2000;  21 (16) 1301-1336
    Google Scholar
  • 42 Anderson D R, Kahn S R, Rodger M A et al.. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial.  JAMA. 2007;  298 (23) 2743-2753
    Google Scholar
  • 43 Schoepf U J, Kucher N, Kipfmueller F, Quiroz R, Costello P, Goldhaber S Z. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism.  Circulation. 2004;  110 (20) 3276-3280
    Google Scholar
  • 44 Van Strijen M J, De Monye W, Kieft G J, Pattynama P M, Prins M H, Huisman M V. Accuracy of single-detector spiral CT in the diagnosis of pulmonary embolism: a prospective multicenter cohort study of consecutive patients with abnormal perfusion scintigraphy.  J Thromb Haemost. 2005;  3 (1) 17-25
    Google Scholar
  • 45 Coche E, Verschuren F, Keyeux A et al.. Diagnosis of acute pulmonary embolism in outpatients: comparison of thin-collimation multi-detector row spiral CT and planar ventilation-perfusion scintigraphy.  Radiology. 2003;  229 (3) 757-765
    Google Scholar
  • 46 Winer-Muram H T, Rydberg J, Johnson M S et al.. Suspected acute pulmonary embolism: evaluation with multi-detector row CT versus digital subtraction pulmonary arteriography.  Radiology. 2004;  233 (3) 806-815
    Google Scholar
  • 47 Stein P D, Fowler S E, Goodman L R PIOPED II Investigators et al. Multidetector computed tomography for acute pulmonary embolism.  N Engl J Med. 2006;  354 (22) 2317-2327
    Google Scholar
  • 48 Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F. Diagnosis and management of subsegmental pulmonary embolism.  J Thromb Haemost. 2006;  4 (4) 724-731
    Google Scholar
  • 49 Stein P D, Chenevert T L, Fowler S E PIOPED III (Prospective Investigation of Pulmonary Embolism Diagnosis III) Investigators et al. Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III).  Ann Intern Med. 2010;  152 (7) 434-443, W142–3
    Google Scholar
  • 50 Smith S B, Geske J B, Maguire J M, Zane N A, Carter R E, Morgenthaler T I. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism.  Chest. 2010;  137 (6) 1382-1390
    Google Scholar
  • 51 Barritt D W, Jordan S C. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial.  Lancet. 1960;  1 (7138) 1309-1312
    Google Scholar
  • 52 Van Ommen C H, Peters M. Acute pulmonary embolism in childhood.  Thromb Res. 2006;  118 (1) 13-25
    Google Scholar
  • 53 Monagle P, Chalmers E, Chan A American College of Chest Physicians et al. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).  Chest. 2008;  133 (6, Suppl) 887S-968S
    Google Scholar
  • 54 Dolovich L R, Ginsberg J S, Douketis J D, Holbrook A M, Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency.  Arch Intern Med. 2000;  160 (2) 181-188
    Google Scholar
  • 55 Malhotra S, Karan R S, Bhargava V K et al.. A meta-analysis of controlled clinical trials comparing low-molecular weight heparins with unfractionated heparin in unstable angina.  Indian Heart J. 2001;  53 (2) 197-202
    Google Scholar
  • 56 Massicotte P, Julian J A, Gent M REVIVE Study Group 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
    Google Scholar
  • 57 Agnelli G, Becattini C. Acute pulmonary embolism.  N Engl J Med. 2010;  363 (3) 266-274
    Google Scholar
  • 58 Come P C. Echocardiographic evaluation of pulmonary embolism and its response to therapeutic interventions.  Chest. 1992;  101 (4, Suppl) 151S-162S
    Google Scholar
  • 59 Albisetti M. Thrombolytic therapy in children.  Thromb Res. 2006;  118 (1) 95-105
    Google Scholar
  • 60 Zenz W, Arlt F, Sodia S, Berghold A. Intracerebral hemorrhage during fibrinolytic therapy in children: a review of the literature of the last thirty years.  Semin Thromb Hemost. 1997;  23 (3) 321-332
    Google Scholar
  • 61 Raffini L. Thrombolysis for intravascular thrombosis in neonates and children.  Curr Opin Pediatr. 2009;  21 (1) 9-14
    Google Scholar
  • 62 Hoffmeister H M, Szabo S, Helber U, Seipel L. The thrombolytic paradox.  Thromb Res. 2001;  103 (Suppl 1) S51-S55
    Google Scholar
  • 63 Jean N, Labombarda F, De La Gastine G, Raisky O, Boudjemline Y. Successful pulmonary embolectomy in a 4-year-old girl with antithrombin III deficiency.  Pediatr Cardiol. 2010;  31 (5) 711-713
    Google Scholar
  • 64 Robinson A, Fellows K E, Bridges N D, Rome J J. Effectiveness of pharmacomechanical thrombolysis in infants and children.  Am J Cardiol. 2001;  87 (4) 496-499, A8
    Google Scholar
  • 65 van Loon R L, Roofthooft M T, van Osch-Gevers M et al.. Clinical characterization of pediatric pulmonary hypertension: complex presentation and diagnosis.  J Pediatr. 2009;  155 (2) 176-182, e1
    Google Scholar
  • 66 Fedullo P F, Auger W R, Kerr K M, Rubin L J. Chronic thromboembolic pulmonary hypertension.  N Engl J Med. 2001;  345 (20) 1465-1472
    Google Scholar
  • 67 Pengo V, Lensing A W, Prins M H Thromboembolic Pulmonary Hypertension Study Group et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism.  N Engl J Med. 2004;  350 (22) 2257-2264
    Google Scholar
  • 68 Binder L, Pieske B, Olschewski M et al.. N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism.  Circulation. 2005;  112 (11) 1573-1579
    Google Scholar

Leonardo R. BrandãoM.D. 

The Hospital for Sick Children

555 University Avenue, Black Wing, Room 10412, Toronto, ON M5G 1X8, Canada

Email: leonardo.brandao@sickkids.ca