Pulmonary embolism and in situ pulmonary artery thrombosis in paediatrics

Madhvi Rajpurkar; Tina T. Biss; Ernest K. Amankwah; Denise Martinez; Suzan Williams; C. Heleen van Ommen; Neil A. Goldenberg

doi:10.1160/TH16-07-0529

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2017; 117(06): 1199-1207
DOI: 10.1160/TH16-07-0529

Stroke, Systemic or Venous thromboembolism

Schattauer GmbH

Pulmonary embolism and in situ pulmonary artery thrombosis in paediatrics

A systematic review

Authors

Madhvi Rajpurkar

¹The Carman and Ann Adams Department of Pediatrics, Division of Hematology Oncology, Wayne State University School of Medicine, Children’s Hospital of Michigan, Detroit, Michigan, USA
Tina T. Biss

²Department of Haematology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Ernest K. Amankwah

³Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

⁴Clinical and Translational Research Organization, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, USA
Denise Martinez

⁴Clinical and Translational Research Organization, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, USA
Suzan Williams

⁵Division of Haematology/Oncology, Department of Paediatrics, Hospital for Sick Children, Toronto & University of Toronto,Toronto, Ontario, Canada
C. Heleen van Ommen

⁶Department of Pediatric Hematology, Erasmus Medical Center Sophia Children’s Hospital, Rotterdam, the Netherlands
Neil A. Goldenberg

⁴Clinical and Translational Research Organization, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, USA

⁷Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine and Johns Hopkins Medicine Pediatric Thrombosis Program, St. Petersburg, Florida and Baltimore, Maryland, USA

Abstract

Summary

Data on paediatric pulmonary embolism (PE) are scarce. We sought to systematically review the current literature on childhood PE and conducted a search on paediatric PE via PubMed (1946–2013) and Embase (1980–2013). There was significant heterogeneity in reported data. Two patterns were noted: classic thromboembolic PE (TE-PE) and in situ pulmonary artery thrombosis (ISPAT). Mean age of presentation for TE-PE was 14.86 years, and 51% of cases were males. The commonest method for diagnosis of TE-PE was contrast CT with angiography (74% of patients). The diagnosis of TE-PE was often delayed. Although 85% of children with TE-PE had an elevated D-dimer at presentation, it was non-discriminatory for the diagnosis. In paediatric TE-PE, the prevalence of central venous catheters was 23%, immobilisation 38%, systemic infection 31% and obesity 13%, elevated Factor VIII or von Willebrand factor levels 27%, Protein C deficiency 17%, Factor V Leiden 14% and Protein S deficiency 7%. In patients with TE-PE, pharmacologic thrombolysis was used in 29%; unfractionated heparin was the most common initial anticoagulant treatment in 64% and low-molecular-weight heparins the most common follow-up treatment in 83%. Duration of anticoagulant therapy was variable and death was reported in 26% of TE-PE patients. In contrast to TE-PE, patients with ISPAT were not investigated systematically for presence of thrombophilia, had more surgical interventions as the initial management and were often treated with anti-platelet medications. This review summarises important data and identifies gaps in the knowledge of paediatric PE, which may help to design future studies.

Keywords

Pulmonary embolism - pulmonary artery thrombosis - paediatrics - children

Full Text

References

References
1 Boulet SL, Amendah D, Grosse SD. et al. Health care expenditures associated with venous thromboembolism among children. Thromb Res 2012; 129: 583-587.
2 Limbrey R, Howard L. Developments in the management and treatment of pulmonary embolism. Eur Resp Rev 2015; 24: 484-497.
3 Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13.
4 Hancock HS, Wang M, Gist KM. et al. Cardiac findings and long-term thromboembolic outcomes following pulmonary embolism in children: a combined retrospective-prospective inception cohort study. Cardiol Young 2013; 23: 344-352.
5 Buck JR, Connors RH, Coon WW. et al. Pulmonary embolism in children. J Ped Surg 1981; 16: 385-391.
6 Bernstein D, Coupey S, Schonberg SK. Pulmonary embolism in adolescents. Am J Dis Child 1986; 140: 667-671.
7 Hoyer PF, Gonda S, Barthels M. et al. Thromboembolic complications in children with nephrotic syndrome. Risk and incidence. Acta Paed Scand 1986; 75: 804-810.
8 Lee EY, Tse SK, Zurakowski D. et al. Children suspected of having pulmonary embolism: multidetector CT pulmonary angiography--thromboembolic risk factors and implications for appropriate use. Radiology 2012; 262: 242-251.
9 Nuss R, Hays T, Chudgar U. et al. Antiphospholipid antibodies and coagulation regulatory protein abnormalities in children with pulmonary emboli. J Ped Hematol/Oncol 1997; 19: 202-207.
10 Rajpurkar M, Warrier I, Chitlur M. et al. Pulmonary embolism-experience at a single children’s hospital. Thromb Res 2007; 119: 699-703.
11 Tavil B, Kuskonmaz B, Kiper N. et al. Pulmonary thromboembolism in childhood: a single-centre experience from Turkey. Heart Lung 2009; 38: 56-65.
12 Victoria T, Mong A, Altes T. et al. Evaluation of pulmonary embolism in a pediatric population with high clinical suspicion. Ped Radiol 2009; 39: 35-41.
13 Zhang LJ, Wang ZJ, Zhou CS. et al. Evaluation of pulmonary embolism in pediatric patients with nephrotic syndrome with dual energy CT pulmonary angiography. Acad Radiol 2012; 19: 341-348.
14 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: 563-565.
15 Raffini L, Huang YS, Witmer C. et al. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics 2009; 124: 1001-1008.
16 Emery JL. Pulmonary Embolism in Children. Arch Dis Child 1962; 37: 591-595.
17 Emery JL. Pulmonary thrombosis and its association with unexpected death in childhood. Arch Dis Child 1953; 28: 187-193.
18 Puranik R, Chow CK, Duflou JA. et al. Sudden death in the young. Heart Rhythm 2005; 2: 1277-1282.
19 Drury RA, Mylius EA. The changing pattern of pulmonary embolism in Ugandan Africans. Afr J Med Sci 1973; 4: 369-381.
20 Sanerkin NG, Edwards P, Jacobs J. Pulmonary thrombo-embolic phenomena in the newborn. J Pathol Bacteriol 1966; 91: 569-574.
21 Athale UH, Nagel K, Khan AA. et al. Thromboembolism in children with lymphoma. Thromb Res 2008; 122: 459-465.
22 Athale U, Siciliano S, Thabane L. et al. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer 2008; 51: 792-797.
23 Paz-Priel I, Long L, Helman LJ. et al. Thromboembolic events in children and young adults with pediatric sarcoma. J Clin Oncol 2007; 25: 1519-1524.
24 Uderzo C, Faccini P, Rovelli A. et al. Pulmonary thromboembolism in childhood leukemia: 8-years’ experience in a pediatric hematology centre. J Clin Oncol 1995; 13: 2805-2812.
25 Goldenberg NA, Branchford B, Wang M. et al. Percutaneous mechanical and pharmacomechanical thrombolysis for occlusive deep vein thrombosis of the proximal limb in adolescent subjects: findings from an institution-based prospective inception cohort study of pediatric venous thromboembolism. J Vasc Interv Radiol 2011; 22: 121-132.
26 Biss TT, Brandao LR, Kahr WH. et al. Clinical features and outcome of pulmonary embolism in children. Br J Haematol 2008; 142: 808-818.
27 Desai MH, Linares HA, Herndon DN. Pulmonary embolism in burned children. Burns 1989; 15: 376-380.
28 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: 1251-1257.
29 Hsu DT, Addonizio LJ, Hordof AJ. et al. Acute pulmonary embolism in pediatric patients awaiting heart transplantation. J Am Coll Cardiol 1991; 17: 1621-1625.
30 van Ommen CH, Heyboer H, Groothoff JW. et al. Persistent tachypnea in children: keep pulmonary embolism in mind. J Ped Hematol/Oncol 1998; 20: 570-573.
31 Dollery CM, Sullivan ID, Bauraind O. et al. Thrombosis and embolism in long-term central venous access for parenteral nutrition. Lancet 1994; 344: 1043-1045.
32 Kosiak M, Korbus-Kosiak A, Kosiak W. et al. Is chest sonography a breakthrough in diagnosis of pulmonary thromboembolism in children?. Ped Pulmonol 2008; 43: 1183-1187.
33 Marraro G, Uderzo C, Marchi P. et al. Acute respiratory failure and pulmonary thrombosis in leukemic children. Cancer 1991; 67: 696-702.
34 Lee EY, Kritsaneepaiboon S, Arellano CM. et al. Unsuspected pulmonary emboli in pediatric oncology patients: detection with MDCT. Am J Roentgenol 2010; 194: 1216-1222.
35 Lee EY, Zucker EJ, Tsai J. et al. Pulmonary MDCT angiography: value of multi-planar reformatted images in detecting pulmonary embolism in children. Am J Roentgenol 2011; 197: 1460-1465.
36 Lee EY, Zurakowski D, Diperna S. et al. Parenchymal and pleural abnormalities in children with and without pulmonary embolism at MDCT pulmonary angiography. Ped Radiol 2010; 40: 173-181.
37 Biss TT, Brandao LR, Kahr WH. et al. Clinical probability score and D-dimer estimation lack utility in the diagnosis of childhood pulmonary embolism. J Thromb Haemost 2009; 7: 1633-1638.
38 Arnold RW, Janitz E, Poulton TB. et al. Pulmonary CT angiography to evaluate for pulmonary embolism in children visiting adult-centreed community hospitals. Am J Roentgenol 2011; 196: W823-830.
39 Sirachainan N, Chuansumrit A, Angchaisuksiri P. et al. Venous thromboembolism in Thai children. Ped Hematol Oncol 2007; 24: 245-256.
40 Machnowska M, Burbridge BE, Fladeland D. Are pretest clinical probability algorithms used before obtaining multidetector computed tomographic pulmonary embolism studies?. Canad Assoc Radiol J 2011; 62: 107-109.
41 Manco-Johnson MJ, Nuss R, Hays T. et al. Combined thrombolytic and anticoagulant therapy for venous thrombosis in children. J Ped 2000; 136: 446-453.
42 Kritsaneepaiboon S, Lee EY, Zurakowski D. et al. MDCT pulmonary angiography evaluation of pulmonary embolism in children. Am J Roentgenol 2009; 192: 1246-1252.
43 Champ C, Byard RW. Pulmonary thromboembolism and unexpected death in infancy. J Paediatr Child Health 1994; 30: 550-551.
44 Hennelly KE, Baskin MN, Monuteuax MC. et al. Detection of Pulmonary Embolism in High-Risk Children. J Pediatr 2016; 178: 214-218.e3.
45 Agha BS, Sturm JJ, Simon HK. et al. Pulmonary embolism in the pediatric emergency department. Pediatrics 2013; 132: 663-667.
46 Tarumi T, Martincic D, Thomas A. et al. Familial thrombophilia associated with fibrinogen paris V: Dusart syndrome. Blood 2000; 96: 1191-1193.
47 Bavare AC, Naik SX, Lin PH. et al. Catheter-directed thrombolysis for severe pulmonary embolism in pediatric patients. Ann Vasc Surg 2014; 28: 1794.e1-7.
48 Sandoval JA, Sheehan MP, Stonerock CE. et al. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg 2008; 47: 837-843.
49 Jimenez D, Lobo JL, Barrios D. et al. Risk stratification of patients with acute symptomatic pulmonary embolism. Intern Emerg Med 2016; 11: 11-18.
50 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (23) (Suppl. 01) I4-8.
51 Zhang S, Zhai Z, Yang Y. et al. Pulmonary embolism risk stratification by European Society of Cardiology is associated with recurrent venous thromboembolism: Findings from a long-term follow-up study. Int J Cardiol 2016; 202: 275-281.
52 Wells PS, Ginsberg JS, Anderson DR. et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998; 129: 997-1005.
53 Klok FA, Mos IC, Nijkeuter M. et al. Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Arch Intern Med 2008; 168: 2131-2136.
54 Kline JA, Courtney DM, Kabrhel C. et al. Prospective multicentre evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost 2008; 6: 772-780.
55 Ibanez-Bravo S, Banzo I, Quirce R. et al. Ventilation/Perfusion SPECT lung scintigraphy and computed tomography pulmonary angiography in patients with clinical suspicion of pulmonary embolism. Rev Esp Med Nucl Imagen Mol 2016 Epub ahead of print.
56 Kappelman MD, Horvath-Puho E, Sandler RS. et al. Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide study. Gut 2011; 60: 937-943.
57 McBride WJ, Gadowski GR, Keller MS. et al. Pulmonary embolism in pediatric trauma patients. J Trauma 1994; 37: 913-915.
58 Truitt AK, Sorrells DL, Halvorson E. et al. Pulmonary embolism: which pediatric trauma patients are at risk?. J Ped Surg 2005; 40: 124-127.
59 Fleming GA, Khan M, Janssen D. et al. Angiojet rheolytic thrombectomy in infants following cardiac surgery. Catheter Cardiovasc Interv 2010; 76: 233-240.
60 Forbes TJ, Rosenthal GL, Reul Jr GR. et al. Risk factors for life-threatening cavopulmonary thrombosis in patients undergoing bidirectional superior cavopulmonary shunt: an exploratory study. Am Heart J 1997; 134: 865-871.
61 Goble MM, Gomez CA. Neonatal pulmonary artery thrombosis: echocardio-graphic characteristics and possible contributing factors. J Am Soc Echocardiogr 2005; 18: 693.
62 Jadhav M, Sapre A, Garekar S. et al. Neonatal pulmonary artery thrombosis. Ann Ped Cardiol 2012; 5: 44-46.
63 Kaestner M, Handke RP, Photiadis J. et al. Implantation of stents as an alternative to reoperation in neonates and infants with acute complications after surgical creation of a systemic-to-pulmonary arterial shunt. Cardiol Young 2008; 18: 177-184.
64 Kim SJ, Kim WH, Lim HG. et al. Outcome of 200 patients after an extracardiac Fontan procedure. J Thoracic Cardiovasc Surg 2008; 136: 108-116.
65 Lee SY, Baek JS, Kim GB. et al. Clinical significance of thrombosis in an intra-cardiac blind pouch after a Fontan operation. Ped Cardiol 2012; 33: 42-48.
66 Li JS, Yow E, Berezny KY. et al. Clinical outcomes of palliative surgery including a systemic-to-pulmonary artery shunt in infants with cyanotic congenital heart disease: does aspirin make a difference?. Circulation 2007; 116: 293-297.
67 Menon SC, Hagler DJ, Cetta F. et al. Rheolytic mechanical thrombectomy for pulmonary artery thrombus in children with complex cyanotic congenital heart disease. Catheter Cardiovasc Interv 2008; 71: 237-243.
68 Tiete AR, Sachweh JS, Roemer U. et al. Right ventricular outflow tract reconstruction with the Contegra bovine jugular vein conduit: a word of caution. Ann Thorac Surg 2004; 77: 2151-2156.