Semin Thromb Hemost 2021; 47(08): 920-930
DOI: 10.1055/s-0041-1729886
Review Article

Venous Thromboembolism in Pediatric Cancer Patients with Central Venous Catheter—A Systematic Review and Meta-analysis

Rasmus Søgaard Hansen
1   Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark
,
Mads Nybo
1   Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark
,
Anne-Mette Hvas
2   Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
3   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
› Institutsangaben
Funding None.

Abstract

Pediatric cancer patients hold an increased risk of venous thromboembolism (VTE) due to their cancer. Central venous catheters (CVCs) further increase the VTE risk. This systematic literature review elucidates the VTE incidence in pediatric cancer patients with CVC. MEDLINE and EMBASE were searched in August 2020 without time limits. We included studies reporting original data on patients ≤18 years with any CVC type and any cancer type, who were examined for VTE with ≥7 days follow-up. In total, 682 unique records were identified, whereof 189 studies were assessed in full text. Altogether, 25 studies were included, containing 2,318 pediatric cancer patients with CVC, of which 17% suffered VTE. Fifteen studies (n = 1,551) described CVC-related VTE and reported 11% CVC-related VTE. Concerning cancer type, 991 children suffered from acute lymphoblastic leukemia (ALL) and 616 from solid tumors. Meta-analysis revealed VTE incidence (95% confidence interval) of 21% (8–37) for ALL and 7% (0.1–17) for solid tumors. Additionally, 20% of children with tunneled or nontunneled CVC and 12% of children with implantable ports suffered VTE. In conclusion, pediatric cancer patients with CVC have substantial VTE risk. Children with ALL and CVC have higher VTE incidence than children with solid tumors and CVC. Implantable port catheter should be preferred over tunneled or nontunneled CVC to reduce VTE risk. Thrombophilia investigation does not seem relevant in pediatric cancer patients with CVC and VTE. To prevent VTE, intensified catheter care is recommended, especially in children with ALL.

Supplementary Material



Publikationsverlauf

Artikel online veröffentlicht:
02. September 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Steliarova-Foucher E, Colombet M, Ries LAG. et al; IICC-3 contributors. International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol 2017; 18 (06) 719-731
  • 2 Trousseau A. Clinique Medicale de l'Hotel-Dieu Paris. London: The New Sydenham Society; . Phlegmasia alba dolens; 1865: 654-712
  • 3 Forbrigger Z, Kuhle S, Brown MM, Moorehead PC, Digout C, Kulkarni K. The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study. Ann Hematol 2018; 97 (10) 1903-1908
  • 4 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 (06) 792-797
  • 5 Ko RH, Thornburg CD. Venous Thromboembolism in Children with Cancer and Blood Disorders. Front Pediatr 2017; 5: 12
  • 6 Bordbar M, Karimi M, Shakibazad N. Thrombosis in pediatric malignancy: a review and future perspectives with focus on management. Blood Coagul Fibrinolysis 2018; 29 (07) 596-601
  • 7 Onyeama SN, Hanson SJ, Dasgupta M, Baker K, Simpson PM, Punzalan RC. Central venous catheter-associated venous thromboembolism in children with hematologic malignancy. J Pediatr Hematol Oncol 2018; 40 (08) e519-e524
  • 8 Giordano P, Saracco P, Grassi M. et al; Italian Association of Pediatric Hematology and Oncology (AIEOP). Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Ann Hematol 2015; 94 (11) 1765-1776
  • 9 Chopra V, Anand S, Hickner A. et al. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet 2013; 382 (9889): 311-325
  • 10 Ahn DH, Illum HB, Wang DH, Sharma A, Dowell JE. Upper extremity venous thrombosis in patients with cancer with peripherally inserted central venous catheters: a retrospective analysis of risk factors. J Oncol Pract 2013; 9 (01) e8-e12
  • 11 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009; 151 (04) 264-269 , W64
  • 12 National Heart, Lung, and Blood Institute. Study Quality Assessment Tools. . Accessed February 19, 2021 at: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
  • 13 Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health 2013; 67 (11) 974-978
  • 14 Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
  • 15 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21 (11) 1539-1558
  • 16 Terrin N, Schmid CH, Lau J, Olkin I. Adjusting for publication bias in the presence of heterogeneity. Stat Med 2003; 22 (13) 2113-2126
  • 17 Schoot RA, van de Wetering MD, Stijnen T. et al; DCOG-Aristocaths Supportive Care Working Group. Prevalence of symptomatic and asymptomatic thrombosis in pediatric oncology patients with tunneled central venous catheters. Pediatr Blood Cancer 2016; 63 (08) 1438-1444
  • 18 Ruud E, Holmstrøm H, De Lange C, Hogstad EM, Wesenberg F. Low-dose warfarin for the prevention of central line-associated thromboses in children with malignancies—a randomized, controlled study. Acta Paediatr 2006; 95 (09) 1053-1059
  • 19 Mitchell LG, Andrew M, Hanna K. et al; Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase Group (PARKAA). A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study. Cancer 2003; 97 (02) 508-516
  • 20 Kalmanti M, Germanakis J, Stiakaki E. et al. Prophylaxis with urokinase in pediatric oncology patients with central venous catheters. Pediatr Hematol Oncol 2002; 19 (03) 173-179
  • 21 Kulkarni K, Halton J, Spavor M. et al. Increased requirement for central venous catheter replacement in paediatric oncology patients with deep venous thrombosis: a multicentre study. Thromb Haemost 2015; 113 (02) 434-435
  • 22 Revel-Vilk S, Yacobovich J, Tamary H. et al. Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer. Cancer 2010; 116 (17) 4197-4205
  • 23 Mitchell L, Lambers M, Flege S. et al. Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study. Blood 2010; 115 (24) 4999-5004
  • 24 Revel-Vilk S, Menahem M, Stoffer C, Weintraub M. Post-thrombotic syndrome after central venous catheter removal in childhood cancer survivors is associated with a history of obstruction. Pediatr Blood Cancer 2010; 55 (01) 153-156
  • 25 Ociepa T, Maloney E, Urasinski T, Sawicki M. Thrombotic complications of tunneled central lines in children with malignancy. J Pediatr Hematol Oncol 2010; 32 (02) 88-92
  • 26 Chung BH, Ma ES, Khong PL, Chan GC. Inherited thrombophilic factors do not increase central venous catheter blockage in children with malignancy. Pediatr Blood Cancer 2008; 51 (04) 509-512
  • 27 Farinasso L, Bertorello N, Garbarini L. et al. Risk factors of central venous lines-related thrombosis in children with acute lymphoblastic leukemia during induction therapy: a prospective study. Leukemia 2007; 21 (03) 552-556
  • 28 Ruud E, Holmstrøm H, de Lange C, Natvig S, Albertsen BK, Wesenberg F. Thrombotic effects of asparaginase in two acute lymphoblastic leukemia protocols (NOPHO ALL-1992 versus NOPHO ALL-2000): a single-institution study. Pediatr Hematol Oncol 2006; 23 (03) 207-216
  • 29 Stiakaki E, Germanakis I, Sfyridaki C, Katzilakis N, Danilatou V, Kalmanti M. Prevalence of Factor V Leiden and other thrombophilic traits among Cretan children with malignancy. Pediatr Blood Cancer 2005; 44 (04) 386-389
  • 30 Male C, Chait P, Andrew M, Hanna K, Julian J, Mitchell L. PARKAA Investigators. Central venous line-related thrombosis in children: association with central venous line location and insertion technique. Blood 2003; 101 (11) 4273-4278
  • 31 Ruud E, Holmstrøm H, Natvig S, Wesenberg F. Prevalence of thrombophilia and central venous catheter-associated neck vein thrombosis in 41 children with cancer—a prospective study. Med Pediatr Oncol 2002; 38 (06) 405-410
  • 32 Glaser DW, Medeiros D, Rollins N, Buchanan GR. Catheter-related thrombosis in children with cancer. J Pediatr 2001; 138 (02) 255-259
  • 33 Stokes DC, Rao BN, Mirro Jr J. et al. Early detection and simplified management of obstructed Hickman and Broviac catheters. J Pediatr Surg 1989; 24 (03) 257-262
  • 34 Wesenberg F, Anker C, Sommerschild H, Flaatten H. Central venous catheter with subcutaneous injection port (Port-A-Cath): clinical experience with children. Pediatr Hematol Oncol 1987; 4 (02) 137-143
  • 35 Pegelow CH, Narvaez M, Toledano SR, Davis J, Oiticica C, Buckner D. Experience with a totally implantable venous device in children. Am J Dis Child 1986; 140 (01) 69-71
  • 36 Östlund Å, Fläring U, Norberg Å. et al. Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters. Br J Anaesth 2019; 123 (03) 316-324
  • 37 Abate ME, Sánchez OE, Boschi R. et al. Analysis of risk factors for central venous catheter-related complications: a prospective observational study in pediatric patients with bone sarcomas. Cancer Nurs 2014; 37 (04) 292-298
  • 38 Albisetti M, Kellenberger CJ, Bergsträsser E. et al. Port-a-cath-related thrombosis and postthrombotic syndrome in pediatric oncology patients. J Pediatr 2013; 163 (05) 1340-1346
  • 39 Rubie H, Juricic M, Claeyssens S. et al. Morbidity using subcutaneous ports and efficacy of vancomycin flushing in cancer. Arch Dis Child 1995; 72 (04) 325-329
  • 40 Previtali P, Paladini S, Gandini L. et al. Role of serial ultrasound screening of venous thrombosis in oncologic children with central lines. Pediatr Hematol Oncol J 2019; 4: 1-6
  • 41 Cassey J, Hendry GM, Patel J. Evaluation of long-term central venous patency in children with chronic venous catheters using image-directed Doppler ultrasonography. J Clin Ultrasound 1994; 22 (05) 313-315
  • 42 Kahale LA, Tsolakian IG, Hakoum MB. et al. Anticoagulation for people with cancer and central venous catheters. Cochrane Database Syst Rev 2018; 6 (06) CD006468
  • 43 Htun KT, Ma MJY, Lee AYY. Incidence and outcomes of catheter related thrombosis (CRT) in patients with acute leukemia using a platelet-adjusted low molecular weight heparin regimen. J Thromb Thrombolysis 2018; 46 (03) 386-392
  • 44 Refaei M, Fernandes B, Brandwein J, Goodyear MD, Pokhrel A, Wu C. Incidence of catheter-related thrombosis in acute leukemia patients: a comparative, retrospective study of the safety of peripherally inserted vs. centrally inserted central venous catheters. Ann Hematol 2016; 95 (12) 2057-2064
  • 45 Al-Asadi O, Almusarhed M, Eldeeb H. Predictive risk factors of venous thromboembolism (VTE) associated with peripherally inserted central catheters (PICC) in ambulant solid cancer patients: retrospective single Centre cohort study. Thromb J 2019; 17: 2
  • 46 Decousus H, Bourmaud A, Fournel P. et al; ONCOCIP Investigators. Cancer-associated thrombosis in patients with implanted ports: a prospective multicenter French cohort study (ONCOCIP). Blood 2018; 132 (07) 707-716
  • 47 Caruso V, Iacoviello L, Di Castelnuovo A. et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood 2006; 108 (07) 2216-2222
  • 48 Raffini L. Thrombophilia in children: who to test, how, when, and why?. Hematology (Am Soc Hematol Educ Program) 2008; 2008: 228-235