Semin intervent Radiol 2012; 29(01): 036-043
DOI: 10.1055/s-0032-1302450
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Deep Vein Thrombosis: Thrombolysis in the Pediatric Population

Lindsey A. Greene
1   Department of Pediatrics, Weill Cornell Medical College, New York, New York
,
Neil A. Goldenberg
2   Children's Hospital Colorado
3   Section of Hematology/Oncology/Bone Marrow Transplant and Center for Cancer and Blood Disorders, Department of Pediatrics
4   Mountain States Regional Hemophilia and Thrombosis Center
5   Division of Hematology/Oncology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, Colorado
› Author Affiliations
Further Information

Publication History

Publication Date:
16 April 2012 (online)

Abstract

Improved medical treatment options have advanced pediatric care but often necessitate both invasive vascular procedures and venous access predisposing these patients to venous thrombotic events. Although pediatric deep vein thrombosis (DVT) is an increasingly recognized phenomenon, high-quality evidence for its antithrombotic treatment in general remains limited, and even more so with respect to thrombolytic therapy. Correspondingly, current American College of Chest Physicians guidelines discourage the routine use of thrombolytic therapy for pediatric DVT; by contrast, American Heart Association guidelines suggest consideration for such therapy in young patients in whom the balance of benefit to risk may be most favorable. The developing hemostatic system and relative rarity of thrombotic events have historically posed impediments to the design and conduction of prospective clinical trials of thrombolysis in children. This narrative review summarizes available information regarding thrombolytic therapy for pediatric DVT.

 
  • References

  • 1 Goldenberg NA, Bernard TJ. Venous thromboembolism in children. Hematol Oncol Clin North Am 2010; 24 (1) 151-166
  • 2 Raffini L. Thrombolysis for intravascular thrombosis in neonates and children. Curr Opin Pediatr 2009; 21 (1) 9-14
  • 3 Vu LT, Nobuhara KK, Lee H, Farmer DL. Determination of risk factors for deep venous thrombosis in hospitalized children. J Pediatr Surg 2008; 43 (6) 1095-1099
  • 4 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 (4) 563-565
  • 5 Goldenberg NA, Durham JD, Knapp-Clevenger R, Manco-Johnson MJ. A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children. Blood 2007; 110 (1) 45-53
  • 6 Goldenberg NA. Long-term outcomes of venous thrombosis in children. Curr Opin Hematol 2005; 12 (5) 370-376
  • 7 Dix D, Andrew M, Marzinotto V , et al. The use of low molecular weight heparin in pediatric patients: a prospective cohort study. J Pediatr 2000; 136 (4) 439-445
  • 8 Massicotte P, Julian JA, Gent M , et al; REVIVE Study Group. 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
  • 9 Prandoni P, Lensing AW, Cogo A , et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125 (1) 1-7
  • 10 Popuri RK, Vedantham S. The role of thrombolysis in the clinical management of deep vein thrombosis. Arterioscler Thromb Vasc Biol 2011; 31 (3) 479-484
  • 11 Manco-Johnson MJ. How I treat venous thrombosis in children. Blood 2006; 107 (1) 21-29
  • 12 Nowak-Göttl U, Junker R, Kreuz W , et al; Childhood Thrombophilia Study Group. Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors. Blood 2001; 97 (4) 858-862
  • 13 Young G, Albisetti M, Bonduel M , et al. Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies. Circulation 2008; 118 (13) 1373-1382
  • 14 Manco-Johnson MJ. Postthrombotic syndrome in children. Acta Haematol 2006; 115 (3-4) 207-213
  • 15 Goldenberg NA, Donadini MP, Kahn SR , et al. Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica 2010; 95 (11) 1952-1959
  • 16 Manco-Johnson MJ, Knapp-Clevenger R, Miller B , et al. Post thrombotic syndrome (PTS) in children: validation of a new pediatric outcome instrument and results in a comprehensive cohort of children with extremity deep vein thrombosis (DVT). Blood 2003; 102: 553a
  • 17 Goldenberg NA, Knapp-Clevenger R, Manco-Johnson MJ ; Mountain States Regional Thrombophilia Group. Elevated plasma factor VIII and D-dimer levels as predictors of poor outcomes of thrombosis in children. N Engl J Med 2004; 351 (11) 1081-1088
  • 18 Goldenberg NA, Branchford B, Wang M, Ray Jr C, Durham JD, Manco-Johnson MJ. 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 (2) 121-132
  • 19 Manco-Johnson MJ, Nuss R, Hays T, Krupski W, Drose J, Manco-Johnson ML. Combined thrombolytic and anticoagulant therapy for venous thrombosis in children. J Pediatr 2000; 136 (4) 446-453
  • 20 Wang M, Hays T, Balasa V , et al; Pediatric Coagulation Consortium. Low-dose tissue plasminogen activator thrombolysis in children. J Pediatr Hematol Oncol 2003; 25 (5) 379-386
  • 21 Albisetti M. Thrombolytic therapy in children. Thromb Res 2006; 118 (1) 95-105
  • 22 Monagle P, Chalmers E, Chan A , 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
  • 23 Jaff MR, McMurtry MS, Archer SL , et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123 (16) 1788-1830
  • 24 Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ ; American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 Suppl) 454S-545S
  • 25 Watson LI, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev 2004; (4) CD002783
  • 26 Enden T, Kløw NE, Sandvik L , et al; CaVenT study group. Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency. J Thromb Haemost 2009; 7 (8) 1268-1275
  • 27 Vedantham S. Preventing pediatric postthrombotic syndrome: preparing the way. J Vasc Interv Radiol 2011; 22 (3) 405-407
  • 28 Yee DL, Chan AK, Williams S, Goldenberg NA, Massicotte MP, Raffini LJ. Varied opinions on thrombolysis for venous thromboembolism in infants and children: findings from a survey of pediatric hematology-oncology specialists. Pediatr Blood Cancer 2009; 53 (6) 960-966
  • 29 Gupta AA, Leaker M, Andrew M , et al. Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children. J Pediatr 2001; 139 (5) 682-688
  • 30 Kukreja K, Vaidya S. Venous interventions in children. Tech Vasc Interv Radiol 2011; 14 (1) 16-21
  • 31 Manco-Johnson MJ, Grabowski EF, Hellgreen M , et al. Recommendations for tPA thrombolysis in children. On behalf of the Scientific Subcommittee on Perinatal and Pediatric Thrombosis of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis. Thromb Haemost 2002; 88 (1) 157-158
  • 32 Saxonhouse MA, Manco-Johnson MJ. The evaluation and management of neonatal coagulation disorders. Semin Perinatol 2009; 33 (1) 52-65
  • 33 Goldenberg NA, Hathaway WE, Jacobson L, Manco-Johnson MJ. A new global assay of coagulation and fibrinolysis. Thromb Res 2005; 116 (4) 345-356
  • 34 Simpson ML, Goldenberg NA, Jacobson LJ, Bombardier CG, Hathaway WE, Manco-Johnson MJ. Simultaneous thrombin and plasmin generation capacities in normal and abnormal states of coagulation and fibrinolysis in children and adults. Thromb Res 2011; 127 (4) 317-323
  • 35 Smith AA, Jacobson LJ, Miller BI, Hathaway WE, Manco-Johnson MJ. A new euglobulin clot lysis assay for global fibrinolysis. Thromb Res 2003; 112 (5-6) 329-337
  • 36 Andrew M, Paes B, Johnston M. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol Oncol 1990; 12 (1) 95-104
  • 37 Andrew M, Brooker L, Leaker M, Paes B, Weitz J. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. Thromb Haemost 1992; 68 (3) 325-330
  • 38 Col JJ, Col-De Beys CM, Renkin JP, Lavenne-Pardonge EM, Bachy JL, Moriau MH. Pharmacokinetics, thrombolytic efficacy and hemorrhagic risk of different streptokinase regimens in heparin-treated acute myocardial infarction. Am J Cardiol 1989; 63 (17) 1185-1192
  • 39 Lynch M, Pentecost BL, Littler WA, Stockley RA. The significance of anti-streptokinase antibodies. Clin Exp Immunol 1994; 96 (3) 427-431
  • 40 Köhler M, Sen S, Miyashita C , et al. Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction. Thromb Res 1991; 62 (1-2) 75-81
  • 41 Pennica D, Holmes WE, Kohr WJ , et al. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 1983; 301 (5897) 214-221
  • 42 Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982; 257 (6) 2912-2919
  • 43 Hoffmeister HM, Szabo S, Helber U, Seipel L. The thrombolytic paradox. Thromb Res 2001; 103 (Suppl. 01) S51-S55
  • 44 Leary SE, Harrod VL, de Alarcon PA, Reiss UM. Low-dose systemic thrombolytic therapy for deep vein thrombosis in pediatric patients. J Pediatr Hematol Oncol 2010; 32 (2) 97-102
  • 45 Laiho MK, Oinonen A, Sugano N , et al. Preservation of venous valve function after catheter-directed and systemic thrombolysis for deep venous thrombosis. Eur J Vasc Endovasc Surg 2004; 28 (4) 391-396
  • 46 Williams MD. Thrombolysis in children. Br J Haematol 2010; 148 (1) 26-36
  • 47 Newall F, Browne M, Savoia H, Campbell J, Barnes C, Monagle P. Assessing the outcome of systemic tissue plasminogen activator for the management of venous and arterial thrombosis in pediatrics. J Pediatr Hematol Oncol 2007; 29 (4) 269-273
  • 48 Bush RL, Lin PH, Bates JT, Mureebe L, Zhou W, Lumsden AB. Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis: safety and feasibility study. J Vasc Surg 2004; 40 (5) 965-970
  • 49 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