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RSM Oct 2007 Thromboprophylaxis in High Risk Children. E A Chalmers Royal Hospital for Sick Children Glasgow
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RSM Oct 2007 VTE in Children & Adolescents. Scope of the problem: Disease Burden Risk Factors Outcomes Prevention: Evidence Guidelines & Strategies.
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RSM Oct 2007 Incidence of VTE in Children Population/Study Cases per 100,000 Adults 25-30 yr 25 – 30 Adults 70 – 79 yr 300 – 500 Canadian Registry 0.7 BPSU Registry 0.6
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RSM Oct 2007 Thrombosis – Age Distribution.
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RSM Oct 2007 Distribution of Peripheral DVT & PE SiteCanadaBPSU Upper limb DVT47 (34%)48 (30%) Lower limb DVT68 (50%)95 (59%) PE 8 (6%) 5 (3%) DVT/PE 14 (10%) 12 (8%) Total Events137160
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RSM Oct 2007 Thrombosis – Risk Factors CVL48% Sepsis32% Immobility28% Malignancy26% Surgery21% TPN12% Renal Disease11% FHx10%
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RSM Oct 2007 Thrombosis – Incidence in Children with Cancer. AuthorConditionIncidence Symptoms Sutor ’99ALL(BFM-90)1.7%100% Nowak-Gottl ‘01 ALL(COALL)2.5%100% Mitchell ’01ALL(PARKAA) 37%1.6% Glazer ’01Cancer 50%25%
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RSM Oct 2007 Thrombosis – Incidence in Children Following Trauma. Incidence: 0.07%-1.9% Risk factors: Older age. Severity of injury (ISS>24). Vascular injury.
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RSM Oct 2007 Childhood VTE – Outcomes OutcomeBPSUCanadaDPSU All cause Mortality 9%9.5%17% Direct Mortality 1.5%2.2%2%
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RSM Oct 2007 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.
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RSM Oct 2007 Prevention of VTE in Children & Adolescents. At Risk Populations: CVL related VTE. Non-CVL related VTE. Methods: Thromboprophylaxis. Mechanical methods.
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RSM Oct 2007 Venous Thrombosis – Risk Factors CVLs are the single most important risk factor for thrombosis in children
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RSM Oct 2007 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)
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RSM Oct 2007 CVL Related Thrombosis. CVLTE IncidenceOdds ratiop-value SC Vein44% 3.140.025 (1.2-8.5) Jugular Vein 20% Percutaneous47% 3.50.011 (1.3-9.2) Cut-down20% SCV/Percutaneous.54% 50.001 (1.9-13.1) TOTAL 33% (28/85) (Male, Blood 2002)
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RSM Oct 2007 Prevention of CVL Related VTE. LMWH(Reviparin)Standard CareNumber (%) Symptomatic VTE3/78(3.8)3/80(3.8) Asymptomatic VTE8/78(10.3)7/80(8.8) Total VTE11/78(14.1)10/80(12.5) Major Bleeding0(0) 1/94(1.1) Minor Bleeding48/90(53.3)41/94(43.6) Death0(0)2/94(2.1) Protekt Study, 2001
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RSM Oct 2007 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
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RSM Oct 2007 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”
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RSM Oct 2007 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
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RSM Oct 2007 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.
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RSM Oct 2007 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.
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