Direct Oral Anticoagulants: Overcoming the Challenges of Managing Venous Thromboembolism in Children

Abstract

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism, is relatively common among adults, with estimated incidence rates ranging from approximately 10 to 1200 per 100 000 adults aged ≥30 years. 1 Raskob G.E. Angchaisuksiri P. Blanco A.N. Büller H. Gallus A. Hunt B.J. et al. Thrombosis: a major contributor to global disease burden. Semin Thromb Hemost. 2014; 40: 724-735 Crossref PubMed Scopus (73) Google Scholar VTE is less common in children than in adults, with estimated incidence rates ranging from 0.7 to 4.9 per 100 000 children. 2 Andrew M. David M. Adams M. Ali K. Anderson R. Barnard D. et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994; 83: 1251-1257 Crossref PubMed Google Scholar , 3 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: 676-681 Abstract Full Text Full Text PDF PubMed Scopus (517) Google Scholar , 4 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: 563-565 Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar , 5 Tuckuviene R. Christensen A.L. Helgestad J. Johnsen S.P. Kristensen S.R. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr. 2011; 159: 663-669 Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar However, it can have serious consequences, such as death, recurrence of thrombosis, loss of vessel patency required for future intravascular cannulation or organ transplantation, chronic pulmonary hypertension, or post-thrombotic syndrome. 2 Andrew M. David M. Adams M. Ali K. Anderson R. Barnard D. et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994; 83: 1251-1257 Crossref PubMed Google Scholar ,6 Goldenberg N.A. Donadini M.P. Kahn S.R. Crowther M. Kenet G. Nowak-Göttl U. et al. Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica. 2010; 95: 1952-1959 Crossref PubMed Scopus (137) Google Scholar , 7 Greene L.A. Goldenberg N.A. Deep vein thrombosis: thrombolysis in the pediatric population. Semin Intervent Radiol. 2012; 29: 36-43 Crossref PubMed Scopus (18) Google Scholar , 8 Pelland-Marcotte M.C. Tucker C. Klaassen A. Avila M.L. Amid A. Amiri N. et al. Outcomes and risk factors of massive and submassive pulmonary embolism in children: a retrospective cohort study. Lancet Haematol. 2019; 6: e144-e153 Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Despite its relative rarity, the incidence of pediatric VTE has increased in recent years. 5 Tuckuviene R. Christensen A.L. Helgestad J. Johnsen S.P. Kristensen S.R. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr. 2011; 159: 663-669 Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar ,9 Sandoval J.A. Sheehan M.P. Stonerock C.E. Shafique S. Rescorla F.J. Dalsing M.C. 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 Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar ,10 Carpenter S.L. Richardson T. Hall M. Increasing rate of pulmonary embolism diagnosed in hospitalized children in the United States from 2001 to 2014. Blood Adv. 2018; 2: 1403-1408 Crossref PubMed Scopus (38) Google Scholar This increase is considered related to a number of factors, including the increased use of central venous catheters (CVCs), improved survival rates for children with chronic or critical conditions, and more frequent VTE diagnoses through improved pediatrician awareness and imaging techniques. 11 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: 1001-1008 Crossref PubMed Scopus (569) Google Scholar ,12 Malec L. Young G. Treatment of venous thromboembolism in pediatric patients. Front Pediatr. 2017; 5: 26 Crossref PubMed Scopus (18) Google Scholar First to the public, next to youThe Journal of PediatricsVol. 240PreviewThanks to direct-to-consumer marketing, snappy jingles, familiar spokespeople, and ubiquitous slogans, you are probably familiar with some direct oral anticoagulants (as well as any number of other classes of medications), such as rivaroxaban (Xarelto) and apixaban (Eliquis). You might not have focused on their use, however, since they were initially developed for use in adults. This volume of The Journal includes a Medical Progress report on direct anticoagulants (DOACs) for use in children with venous thromboembolism, including data from the latest trials and projected approval by the US Food and Drug Administration. Full-Text PDF