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

2. Goals  Discuss incidence and risk factors for CVC related VTE  Determine whether there is evidence for pharmacologic VTE prophylaxis in pediatric population with CVCs

3. Definitions  DVT= thrombosis of internal jugular vein or deep veins of extremities  VTE= DVT or pulmonary embolism  CVC= intravenous catheter inserted through a large vein and ending in the vena cava or right atrium  Thrombosis/VTE vs catheter occlusion: Thrombosis= clot in vessel, occlusion=clot only in catheter

4. Venous thromboembolism  Virchow’s triad

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

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

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

10. Physiology  Lower risk of VTE in children

11. 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)

12.  Incidence of VTE in children with CVC is 25-40%  Multi lumen> single lumen  Femoral> Internal Jugular> Subclavian

13. Is VTE prophylaxis indicated in children with central lines?

14. 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

15. PROphylaxis of ThromboEmbolism in Kids Trial (PROTEKT)  Population: Patients 36 wk GA-18 y with first CVC  Intervention/comparison: Randomized to systemic doses of LMWH or standard care  Outcomes:  Clinically significant VTE, or DVT on exit venogram (day 30 or day of line removal)  Major bleeding event

17. 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

18.  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

21. Conclusions  Based on current evidence, systemic administration of unfractionated heparin or LMWH does not decrease VTE risk in children with CVC

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