Skip to main content
Top
Published in: Pediatric Cardiology 7/2019

01-10-2019 | Dabigatran | Review Article

Direct Oral Anticoagulants: Novel Approach for the Treatment of Thrombosis in Pediatric Patients?

Authors: Ján Mikler, Matej Samoš, Tomáš Bolek, Ingrid Škorňová, Lucia Stančiaková, Ján Staško, Marián Mokáň

Published in: Pediatric Cardiology | Issue 7/2019

Login to get access

Abstract

Venous thromboembolism (VTE) is a rare, but life-threatening disease in those who have not reached their adulthood. This condition is usually treated with heparin or low molecular weight heparins which require parenteral administration and, in case of unfractionated heparin, also frequent laboratory monitoring and dose adjustment. Direct oral anticoagulants (DOACs)—direct thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors rivaroxaban, apixaban, and edoxaban—are currently frequently used for the prevention and treatment of VTE in adult population. In fact, these agents offer several advantages compared to traditional agents, such as oral route of administration, short on-set and off-set of action, predictable pharmacologic profile with low risk of food and drug interactions, and no need for routine laboratory assessment of anticoagulant activity. However, clinical experience with these directly acting oral anticoagulants in pediatric population is very limited as these drugs had been tested and are used mostly in adult individuals. This article reviews the current data from pre- and post-marketing studies reporting the use of DOACs for the treatment of VTE in pediatric patients.
Literature
4.
go back to reference Antonijevic NM, Zivkovic ID, Jovanovic LM, Matic DM, Kocica MJ, Mrdovic IB, Kanjuh VI, Culafic MD (2017) Dabigatran—metabolism, pharmacologic properties and drug interactions. Curr Drug Metab 18:622–635CrossRefPubMed Antonijevic NM, Zivkovic ID, Jovanovic LM, Matic DM, Kocica MJ, Mrdovic IB, Kanjuh VI, Culafic MD (2017) Dabigatran—metabolism, pharmacologic properties and drug interactions. Curr Drug Metab 18:622–635CrossRefPubMed
5.
go back to reference Kvasnicka T, Malikova I, Zenahlikova Z, Kettnerova K, Brzezkova R, Zima T, Ulrych J, Briza J, Netuka I, Kvasnicka J (2017) Rivaroxaban—metabolism, pharmacologic properties and drug interactions. Curr Drug Metab 18:636–642CrossRefPubMed Kvasnicka T, Malikova I, Zenahlikova Z, Kettnerova K, Brzezkova R, Zima T, Ulrych J, Briza J, Netuka I, Kvasnicka J (2017) Rivaroxaban—metabolism, pharmacologic properties and drug interactions. Curr Drug Metab 18:636–642CrossRefPubMed
6.
go back to reference Kubisz P, Stanciakova L, Dobrotova M, Samos M, Mokan M, Stasko J (2017) Apixaban—metabolism, pharmacologic properties and drug interactions. Curr Drug Metab 18:609–621PubMed Kubisz P, Stanciakova L, Dobrotova M, Samos M, Mokan M, Stasko J (2017) Apixaban—metabolism, pharmacologic properties and drug interactions. Curr Drug Metab 18:609–621PubMed
8.
go back to reference Thoenes M, Minguet J, Bramlage K, Bramlage P, Ferrero C (2016) Betrixaban—the next direct factor Xa inhibitor? Expert Rev Hematol 9:1111–1117CrossRefPubMed Thoenes M, Minguet J, Bramlage K, Bramlage P, Ferrero C (2016) Betrixaban—the next direct factor Xa inhibitor? Expert Rev Hematol 9:1111–1117CrossRefPubMed
10.
go back to reference Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ, RE-COVER Study Group (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361:2342–2352CrossRefPubMed Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ, RE-COVER Study Group (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361:2342–2352CrossRefPubMed
11.
go back to reference Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ, RE-MEDY Trial Investigators, RE-SONATE Trial Investigators (2013) Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 368:709–718CrossRefPubMed Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ, RE-MEDY Trial Investigators, RE-SONATE Trial Investigators (2013) Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 368:709–718CrossRefPubMed
12.
go back to reference Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S, EINSTEIN Investigators (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510CrossRefPubMed Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S, EINSTEIN Investigators (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510CrossRefPubMed
13.
go back to reference Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A, EINSTEIN-PE Investigators (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297CrossRefPubMed Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A, EINSTEIN-PE Investigators (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297CrossRefPubMed
14.
go back to reference Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P, EINSTEIN CHOICE Investigators (2017) Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 376:1211–1222CrossRefPubMed Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P, EINSTEIN CHOICE Investigators (2017) Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 376:1211–1222CrossRefPubMed
15.
go back to reference Siontis KC, Zhang X, Eckard A, Bhave N, Schaubel DE, He K, Tilea A, Stack AG, Balkrishnan R, Yao X, Noseworthy PA, Shah ND, Saran R, Nallamothu BK (2018) Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation 138:1519–1529CrossRefPubMedPubMedCentral Siontis KC, Zhang X, Eckard A, Bhave N, Schaubel DE, He K, Tilea A, Stack AG, Balkrishnan R, Yao X, Noseworthy PA, Shah ND, Saran R, Nallamothu BK (2018) Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation 138:1519–1529CrossRefPubMedPubMedCentral
16.
go back to reference Bolek T, Samoš M, Škorňová I, Stančiaková L, Staško J, Korpallová B, Galajda P, Kubisz P, Mokáň M (2019) Does proton pump inhibition change the on-treatment anti-Xa activity in xabans-treated patients with atrial fibrillation? A pilot study. J Thromb Thrombolysis 47:140–145CrossRefPubMed Bolek T, Samoš M, Škorňová I, Stančiaková L, Staško J, Korpallová B, Galajda P, Kubisz P, Mokáň M (2019) Does proton pump inhibition change the on-treatment anti-Xa activity in xabans-treated patients with atrial fibrillation? A pilot study. J Thromb Thrombolysis 47:140–145CrossRefPubMed
17.
go back to reference Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI, AMPLIFY Investigators (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808CrossRefPubMed Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI, AMPLIFY Investigators (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808CrossRefPubMed
18.
go back to reference Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI, AMPLIFY-EXT Investigators (2013) Apixaban for extended treatment of venous thromboembolism. N Engl J Med 368:699–708CrossRefPubMed Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI, AMPLIFY-EXT Investigators (2013) Apixaban for extended treatment of venous thromboembolism. N Engl J Med 368:699–708CrossRefPubMed
19.
go back to reference Lip GY, Agnelli G (2014) Edoxaban: a focused review of its clinical pharmacology. Eur Heart J 35:1844–1855CrossRefPubMed Lip GY, Agnelli G (2014) Edoxaban: a focused review of its clinical pharmacology. Eur Heart J 35:1844–1855CrossRefPubMed
20.
go back to reference Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415CrossRef Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415CrossRef
21.
go back to reference Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM, APEX Investigators (2016) Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med 375:534–544CrossRefPubMed Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM, APEX Investigators (2016) Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med 375:534–544CrossRefPubMed
22.
23.
go back to reference Nossair FF, Chan HHW, Gantioqui J, Atkinson HM, Berry LR, Chan AKC (2017) In-vitro assessment of the effect of dabigatran on thrombosis of adult and neonatal plasma: comparisons using thromboelastography and microscopic visualization of fibrin clot structure. Blood Coagul Fibrinolysis 28:551–557CrossRefPubMed Nossair FF, Chan HHW, Gantioqui J, Atkinson HM, Berry LR, Chan AKC (2017) In-vitro assessment of the effect of dabigatran on thrombosis of adult and neonatal plasma: comparisons using thromboelastography and microscopic visualization of fibrin clot structure. Blood Coagul Fibrinolysis 28:551–557CrossRefPubMed
24.
go back to reference Dietrich K, Stang L, van Ryn J, Mitchell LG (2015) Assessing the anticoagulant effect of dabigatran in children: an in vitro study. Thromb Res 135:630–635CrossRefPubMed Dietrich K, Stang L, van Ryn J, Mitchell LG (2015) Assessing the anticoagulant effect of dabigatran in children: an in vitro study. Thromb Res 135:630–635CrossRefPubMed
25.
go back to reference von Vajna E, Alam R, So TY (2016) Current clinical trials on the use of direct oral anticoagulants in the pediatric population. Cardiol Ther 5:19–41CrossRef von Vajna E, Alam R, So TY (2016) Current clinical trials on the use of direct oral anticoagulants in the pediatric population. Cardiol Ther 5:19–41CrossRef
26.
go back to reference Halton JML, Albisetti M, Biss B, Bomgaars L, Brueckmann M, Gropper S, Harper R, Huang F, Luciani M, Maas H, Tartakovsky I, Mitchell LG (2017) Phase IIa study of dabigatran etexilate in children with venous thrombosis: pharmacokinetics, safety, and tolerability. J Thromb Haemost 15:2147–2157CrossRefPubMed Halton JML, Albisetti M, Biss B, Bomgaars L, Brueckmann M, Gropper S, Harper R, Huang F, Luciani M, Maas H, Tartakovsky I, Mitchell LG (2017) Phase IIa study of dabigatran etexilate in children with venous thrombosis: pharmacokinetics, safety, and tolerability. J Thromb Haemost 15:2147–2157CrossRefPubMed
27.
go back to reference Boehringer Ingelheim (2000) Open label study comparing efficacy and safety of dabigatran etexilate to standard of care in paediatric patients with venous thromboembolism (VTE). In: ClinicalTrials.gov [internet]. National Library of Medicine (US), Bethesda [cited 2015 Jun 15]. NLM identifier: NCT01895777 Boehringer Ingelheim (2000) Open label study comparing efficacy and safety of dabigatran etexilate to standard of care in paediatric patients with venous thromboembolism (VTE). In: ClinicalTrials.gov [internet]. National Library of Medicine (US), Bethesda [cited 2015 Jun 15]. NLM identifier: NCT01895777
28.
go back to reference Boehringer Ingelheim (2000) Safety of dabigatran etexilate in blood clot prevention in children. In: ClinicalTrials.gov [internet]. National Library of Medicine (US), Bethesda. NLM identifier: NCT02197416 Boehringer Ingelheim (2000) Safety of dabigatran etexilate in blood clot prevention in children. In: ClinicalTrials.gov [internet]. National Library of Medicine (US), Bethesda. NLM identifier: NCT02197416
29.
go back to reference Shapiro S, Bhatnagar N, Khan A, Beavis J, Keeling D (2018) Idarucizumab for dabigatran overdose in a child. Br J Haematol 180:457–459CrossRefPubMed Shapiro S, Bhatnagar N, Khan A, Beavis J, Keeling D (2018) Idarucizumab for dabigatran overdose in a child. Br J Haematol 180:457–459CrossRefPubMed
30.
go back to reference Martinelli I, Bucciarelli P, Artoni A, Fossali EF, Passamonti SM, Tripodi A, Peyvandi F (2013) Anticoagulant treatment with rivaroxaban in severe protein S deficiency. Pediatrics 132:e1435–e1439CrossRefPubMed Martinelli I, Bucciarelli P, Artoni A, Fossali EF, Passamonti SM, Tripodi A, Peyvandi F (2013) Anticoagulant treatment with rivaroxaban in severe protein S deficiency. Pediatrics 132:e1435–e1439CrossRefPubMed
31.
go back to reference Van Bruwaene L, Huisman A, Urbanus RT, Versluys B (2016) Heparin-resistant thrombosis due to homozygous antithrombin deficiency treated with rivaroxaban: a case report. J Pediatr Hematol Oncol 38:658–660CrossRefPubMed Van Bruwaene L, Huisman A, Urbanus RT, Versluys B (2016) Heparin-resistant thrombosis due to homozygous antithrombin deficiency treated with rivaroxaban: a case report. J Pediatr Hematol Oncol 38:658–660CrossRefPubMed
32.
go back to reference Ma JY, Zhang X, Li XF, He LJ, Ma N, Wei YY, Wu RH, Wang FY (2018) Thrombotic storm in a 4-year-old boy with a thrombus in the right atrium. Int J Immunopathol Pharmacol. 32:2058738418778121CrossRefPubMedPubMedCentral Ma JY, Zhang X, Li XF, He LJ, Ma N, Wei YY, Wu RH, Wang FY (2018) Thrombotic storm in a 4-year-old boy with a thrombus in the right atrium. Int J Immunopathol Pharmacol. 32:2058738418778121CrossRefPubMedPubMedCentral
33.
go back to reference Attard C, Monagle P, Kubitza D, Ignjatovic V (2012) The in vitro anticoagulant effect of rivaroxaban in children. Thromb Res 130:804–807CrossRefPubMed Attard C, Monagle P, Kubitza D, Ignjatovic V (2012) The in vitro anticoagulant effect of rivaroxaban in children. Thromb Res 130:804–807CrossRefPubMed
34.
go back to reference Attard C, Monagle P, Kubitza D, Ignjatovic V (2014) The in-vitro anticoagulant effect of rivaroxaban in neonates. Blood Coagul Fibrinolysis 25:237–240CrossRefPubMed Attard C, Monagle P, Kubitza D, Ignjatovic V (2014) The in-vitro anticoagulant effect of rivaroxaban in neonates. Blood Coagul Fibrinolysis 25:237–240CrossRefPubMed
35.
go back to reference Beyer-Westendorf J, Gehrisch S (2014) Phamacokinetics of rivaroxaban in adolescents. Hamostaseologie 34:85–87CrossRefPubMed Beyer-Westendorf J, Gehrisch S (2014) Phamacokinetics of rivaroxaban in adolescents. Hamostaseologie 34:85–87CrossRefPubMed
36.
go back to reference Kubitza D, Willmann S, Becka M, Thelen K, Young G, Brandão LR, Monagle P, Male C, Chan A, Kennet G, Martinelli I, Saracco P, Lensing AWA (2018) Exploratory evaluation of pharmacodynamics, pharmacokinetics and safety of rivaroxaban in children and adolescents: an EINSTEIN-Jr phase I study. Thromb J 16:31CrossRefPubMedPubMedCentral Kubitza D, Willmann S, Becka M, Thelen K, Young G, Brandão LR, Monagle P, Male C, Chan A, Kennet G, Martinelli I, Saracco P, Lensing AWA (2018) Exploratory evaluation of pharmacodynamics, pharmacokinetics and safety of rivaroxaban in children and adolescents: an EINSTEIN-Jr phase I study. Thromb J 16:31CrossRefPubMedPubMedCentral
37.
go back to reference Bayer (2000) EINSTEIN Junior Phase II: oral rivaroxaban in young children with venous thrombosis (EINSTEINJr). In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM Identifier: NCT02309411 Bayer (2000) EINSTEIN Junior Phase II: oral rivaroxaban in young children with venous thrombosis (EINSTEINJr). In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM Identifier: NCT02309411
38.
go back to reference Bayer (2000) Oral rivaroxaban in children with venous thrombosis (EINSTEINJunior). In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM Identifier: 01684423 Bayer (2000) Oral rivaroxaban in children with venous thrombosis (EINSTEINJunior). In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM Identifier: 01684423
39.
go back to reference Lensing AWA, Male C, Young G, Kubitza D, Kenet G, Patricia Massicotte M, Chan A, Molinari AC, Nowak-Goettl U, Pap ÁF, Adalbo I, Smith WT, Mason A, Thelen K, Berkowitz SD, Crowther M, Schmidt S, Price V, Prins MH, Monagle P (2018) Rivaroxaban versus standard anticoagulation for acute venous thromboembolism in childhood. Design of the EINSTEIN-Jr phase III study. Thromb J 16:34CrossRefPubMedPubMedCentral Lensing AWA, Male C, Young G, Kubitza D, Kenet G, Patricia Massicotte M, Chan A, Molinari AC, Nowak-Goettl U, Pap ÁF, Adalbo I, Smith WT, Mason A, Thelen K, Berkowitz SD, Crowther M, Schmidt S, Price V, Prins MH, Monagle P (2018) Rivaroxaban versus standard anticoagulation for acute venous thromboembolism in childhood. Design of the EINSTEIN-Jr phase III study. Thromb J 16:34CrossRefPubMedPubMedCentral
40.
go back to reference Weirthein J, Scolnik D, Milshtein NY, Capua T, Glatstein M (2019) Accidental rivaroxaban intoxication in a boy: some lessons in managing new oral anticoagulants in children. Pediatr Emerg Care 35:e44–e46CrossRefPubMed Weirthein J, Scolnik D, Milshtein NY, Capua T, Glatstein M (2019) Accidental rivaroxaban intoxication in a boy: some lessons in managing new oral anticoagulants in children. Pediatr Emerg Care 35:e44–e46CrossRefPubMed
41.
go back to reference Bristol-Myers Squibb (2000) Study to evaluate a single dose of apixaban in pediatric subjects at risk for a thrombotic disorder. In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM Identifier: NCT01707394 Bristol-Myers Squibb (2000) Study to evaluate a single dose of apixaban in pediatric subjects at risk for a thrombotic disorder. In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM Identifier: NCT01707394
42.
go back to reference O’Brien SH, Li D, Mitchell LG, Hess T, Zee P, Yee DL, Newburger JW, Sung L, Rodriguez V (2019) PREVAPIX-ALL: apixaban compared to standard of care for prevention of venous thrombosis in paediatric acute lymphoblastic leukaemia (all)-rationale and design. Thromb Haemost 119:844–853CrossRefPubMed O’Brien SH, Li D, Mitchell LG, Hess T, Zee P, Yee DL, Newburger JW, Sung L, Rodriguez V (2019) PREVAPIX-ALL: apixaban compared to standard of care for prevention of venous thrombosis in paediatric acute lymphoblastic leukaemia (all)-rationale and design. Thromb Haemost 119:844–853CrossRefPubMed
43.
go back to reference Daiichi Sanyko (2000) A Phase 1, open-label, single-dose, non-randomized study to evaluate pharmacokinetics and pharmacodynamics of edoxaban in pediatric patients. In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM identifier: NCT02303431 Daiichi Sanyko (2000) A Phase 1, open-label, single-dose, non-randomized study to evaluate pharmacokinetics and pharmacodynamics of edoxaban in pediatric patients. In: ClinicalTrials.gov. National Library of Medicine (US), Bethesda. NLM identifier: NCT02303431
44.
go back to reference Samoš M, Stančiaková L, Škornova I, Bolek T, Kovar F, Stasko J, Galajda P, Mokan M, Kubisz P (2017) Review of the pharmacology of the emerging possibilities of the direct oral anticoagulants’ reversal. Curr Drug Metab 18:643–650CrossRefPubMed Samoš M, Stančiaková L, Škornova I, Bolek T, Kovar F, Stasko J, Galajda P, Mokan M, Kubisz P (2017) Review of the pharmacology of the emerging possibilities of the direct oral anticoagulants’ reversal. Curr Drug Metab 18:643–650CrossRefPubMed
45.
go back to reference Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI (2017) Idarucizumab for dabigatran reversal—full cohort analysis. N Engl J Med 377:431–441CrossRefPubMed Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI (2017) Idarucizumab for dabigatran reversal—full cohort analysis. N Engl J Med 377:431–441CrossRefPubMed
46.
go back to reference Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Demchuk AM, Pallin DJ, Concha M, Goodman S, Leeds J, Souza S, Siegal DM, Zotova E, Meeks B, Ahmad S, Nakamya J, Milling TJ Jr, ANNEXA-4 Investigators (2019) Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med 380:1326–1335CrossRefPubMedPubMedCentral Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Demchuk AM, Pallin DJ, Concha M, Goodman S, Leeds J, Souza S, Siegal DM, Zotova E, Meeks B, Ahmad S, Nakamya J, Milling TJ Jr, ANNEXA-4 Investigators (2019) Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med 380:1326–1335CrossRefPubMedPubMedCentral
Metadata
Title
Direct Oral Anticoagulants: Novel Approach for the Treatment of Thrombosis in Pediatric Patients?
Authors
Ján Mikler
Matej Samoš
Tomáš Bolek
Ingrid Škorňová
Lucia Stančiaková
Ján Staško
Marián Mokáň
Publication date
01-10-2019
Publisher
Springer US
Published in
Pediatric Cardiology / Issue 7/2019
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-019-02159-3

Other articles of this Issue 7/2019

Pediatric Cardiology 7/2019 Go to the issue