1. Maile Parker, MSIV University of Washington School of Medicine Sept. 27, 2012 Prevention of Venous Thromboembolism and Catheter Occlusion in Pediatric Patients With Central Venous Catheters

2. Case: TE  2 y/o male with stage 4 neuroblastoma presents with painful, swollen left lower extremity s/p placement of femoral apheresis catheter

3. Goals  Determine whether there is evidence for pharmacologic VTE prophylaxis in pediatric population with CVCs  Determine whether there is evidence for pharmacologic prevention of CVC occlusion

4. Venous thromboembolism  Virchow’s triad

6.  Contrast venography (gold standard)  Venous duplex

7. Risk factors  Malignancy  Older age  OCP/pregnancy  Central venous access  Immobility >72 h  Long bone fractures/surgery  Spinal cord injury  Congenital prothrombotic risk factors

8. Pediatric population  Incidence of VTE in children poorly characterized  Lack of consensus/guidelines regarding risk stratification and prophylaxis in children

9. Epidemiology  Incidence: 0.07-0.14/10,000 children/year, 5/10,000 hospital admissions  Mortality rate ~ 2%  2/3 of VTEs diagnosed in children are associated with central venous catheters (CVC)  Incidence of VTE in children with CVC is 25-40%  Femoral>jugular>subclavian  Multi lumen> single lumen

10. Physiology  Lower risk of VTE in children  bleeding time longer in children <10 years of life  Significantly decreased leves of coagulant factors II, V, VII, IX, X, XI, XII  α 2M and C 1-Inh inhibitor levels elevated in childhood, protein C levels were low

11. 2 RCTs regarding chemoprophylaxis of CVC related thrombosis in kids: Massicotte P, Julian JA, Gent M; et al. PROTEKT Study Group, An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line-related thrombotic complications in children: the PROTEKT trial, Thromb Res 2003 1092-3 101-108

12. PROTEKT trial  Population: Patients 36 wk GA-18 y with first CVC  Intervention/comparison: Randomized to LMWH or no treatment  Outcomes:  Clinically significant VTE, or DVT on exit venogram (day 30 or day of line removal)  Major bleeding event

14. Schroeder AR, Axelrod DM et al; A continuous heparin infusion does not prevent catheter- related thrombosis in infants after cardiac surgery, Pediatric Critical Care Med 2010 114 489-495

15.  Population: 90 infants <1 y/o undergoing cardiac surgery  Intervention/comparison: Continuous 10 unit/kg/h heparin infusion vs placebo  Outcomes:  catheter thrombosis  catheter malfunction  bleeding

18. Heparin infusion to prevent CVC occlusion Shah PS, Shah VS. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database of Systematic Reviews 2008, Issue 2.

19.  3 studies  Population: Neonates with PICC  Intervention/comparison: Continuous unfractionated heparin 0.5-1 unit/kg/h  Outcomes:  Catheter occlusion  Thrombosis  Sepsis  Bleeding

21. Conclusions  Based on current evidence, systemic administration of unfractionated heparin or LMWH does not decrease VTE risk in children with CVC  Heparin infusion at low dose prevents catheter occlusion in children

22. References Sandoval, John A, Sheehan, Michael P, Stonerock, Charles E, Shafique, Shoaib, Rescorla, Frederick J, Dalsing, Michael C. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: An increasing population at risk. Journal of Vascular Surgery, Volume 47, Issue 4, April 2008, Pages 837–843 Brian W. Gray, Raquel Gonzalez, Kavita S. Warrier, Lauren A. Stephens, Robert A. Drongowski, Steven W. Pipe, George B. Mychaliska, Characterization of central venous catheter–associated deep venous thrombosis in infants, Journal of Pediatric Surgery, Volume 47, Issue 6, June 2012, Pages 1159-1166 Paul Monagle, MBBS, MD, FCCP; Anthony K. C. Chan, MBBS; Neil A. Goldenberg, MD, PhD; Rebecca N. Ichord, MD; Janna M. Journeycake, MD, MSCS; Ulrike Nowak-Göttl, MD; Sara K. Vesely, PhD. Antithrombotic Therapy in Neonates and Children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST, 2012, Volume 141, Issue 2, No. 2 suppl Massicotte P, Julian JA, Gent M; et al. PROTEKT Study Group, An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line-related thrombotic complications in children: the PROTEKT trial, Thromb Res 2003 1092-3 101-108 Schroeder AR, Axelrod DM, Silverman NH, Rubesova E, Merkel E, Roth SJ; A continuous heparin infusion does not prevent catheter-related thrombosis in infants after cardiac surgery, Pediatr Crit Care Med 2010 114 489-495 Shah PS, Shah VS. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database of Systematic Reviews 2008, Issue 2.