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Thromboprophylaxis in High Risk Children.

Thromboprophylaxis in High Risk Children. E A Chalmers Royal Hospital for Sick Children Glasgow. VTE in Children & Adolescents. Scope of the problem: Disease Burden Risk Factors Outcomes Prevention: Evidence Guidelines & Strategies. Incidence of VTE in Children.

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Thromboprophylaxis in High Risk Children.

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  1. Thromboprophylaxis in High Risk Children. E A Chalmers Royal Hospital for Sick Children Glasgow RSM Oct 2007

  2. VTE in Children & Adolescents. Scope of the problem: • Disease Burden • Risk Factors • Outcomes Prevention: • Evidence • Guidelines & Strategies. RSM Oct 2007

  3. Incidence of VTE in Children RSM Oct 2007

  4. Thrombosis – Age Distribution. RSM Oct 2007

  5. Distribution of Peripheral DVT & PE RSM Oct 2007

  6. Thrombosis – Risk Factors • CVL 48% • Sepsis 32% • Immobility 28% • Malignancy 26% • Surgery 21% • TPN 12% • Renal Disease 11% • FHx 10% RSM Oct 2007

  7. Thrombosis – Incidence in Children with Cancer. Author Condition Incidence Symptoms Sutor ’99 ALL(BFM-90) 1.7% 100% Nowak-Gottl ‘01 ALL(COALL) 2.5% 100% Mitchell ’01 ALL(PARKAA) 37% 1.6% Glazer ’01 Cancer 50% 25% RSM Oct 2007

  8. Thrombosis – Incidence in Children Following Trauma. • Incidence: • 0.07%-1.9% • Risk factors: • Older age. • Severity of injury (ISS>24). • Vascular injury. RSM Oct 2007

  9. Childhood VTE – Outcomes RSM Oct 2007

  10. Childhood VTE – Outcomes • Morbidity: • Symptoms related to site of thrombosis • Loss of central venous access • Recurrent thrombosis • 8% at 3 yrs – follow up of Canadian Registry. • Post thrombotic syndrome (PTS) • 9-17% in recent studies. RSM Oct 2007

  11. Prevention of VTE in Children & Adolescents. • At Risk Populations: • CVL related VTE. • Non-CVL related VTE. • Methods: • Thromboprophylaxis. • Mechanical methods. RSM Oct 2007

  12. Venous Thrombosis – Risk Factors • CVLs are the single most important risk factor for thrombosis in children RSM Oct 2007

  13. CVL/VTE – Site & Other CVL Related Features • Incidence of VTE was highest with femoral & subclavian lines (p=0.014) • Incidence of VTE was independent of: • Catheter type • Catheter size • Duration of placement (up to 50 days) RSM Oct 2007

  14. CVL Related Thrombosis. CVLTE IncidenceOdds ratio p-value SC Vein 44% 3.14 0.025 (1.2-8.5) Jugular Vein 20% Percutaneous 47% 3.5 0.011 (1.3-9.2) Cut-down 20% SCV/Percutaneous. 54% 5 0.001 (1.9-13.1) TOTAL 33% (28/85) (Male, Blood 2002) RSM Oct 2007

  15. Prevention of CVL Related VTE. LMWH(Reviparin) Standard Care Number (%) Number (%) Symptomatic VTE3/78 (3.8) 3/80 (3.8) Asymptomatic VTE 8/78 (10.3) 7/80 (8.8) Total VTE 11/78 (14.1) 10/80 (12.5) Major Bleeding 0 (0) 1/94 (1.1) Minor Bleeding 48/90 (53.3) 41/94 (43.6) Death 0 (0) 2/94 (2.1) Protekt Study, 2001 RSM Oct 2007

  16. Prevention of CVL Related VTE in Children with Leukaemia. • Study design: • RCT low dose warfarin vs control • Endpoints: • Jugular VTE at 1, 3, 6 months by USS • Enrollment: • Patients =29 Controls = 33; Total 62 • Study outcome: • Trial stopped after interim analysis • No differnce between to groups • Problems: • LD warfarin arm – • Frequent sub-therapeutic INRs Rudd, Acta Paediatrica, 2006 RSM Oct 2007

  17. ACCP Guidelines. • Recommend: • “against the use of routine systematic thromboprophylaxis for children with CVLs” • Recommend: • “consideration of thromboprophylaxis for children receiving long term home TPN using VKA” RSM Oct 2007

  18. Antithrombin for Prevention of Thrombosis in ALL • Coagulopathy during ALL therapy: • Multifactorial – effects of steriods & asparaginse. • Reduced antithrombin. • Antithrombin replacement – PARKAA study: • Antithrombin replacement during induction. • Trend towards protective clinical effect in AT treated group: VTE 28% vs 37%. • No benefit in surrogate markers of thrombin generation RSM Oct 2007

  19. Prevention of Non-CVL Related VTE. • No clinical trials. • Current practice: variable & ad hoc. • Association of Paediatric Anaesthetists. • Strategies on identifying those at high risk. • Requires consensus on who should be considered for prophylaxis. • e.g. adolescents with other risk factors. RSM Oct 2007

  20. Future Directions. • Better data collection on the incidence of VTE in specific populations. • Development of scoring systems to identify those at highest risk. • Clinical trials of thromboprophylaxis – utilization of new agents. RSM Oct 2007

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