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

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

RSM Oct 2007 Incidence of VTE in Children Population/Study Cases per 100,000 Adults yr 25 – 30 Adults 70 – 79 yr 300 – 500 Canadian Registry 0.7 BPSU Registry 0.6

RSM Oct 2007 Thrombosis – Age Distribution.

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

RSM Oct 2007 Thrombosis – Risk Factors  CVL48%  Sepsis32%  Immobility28%  Malignancy26%  Surgery21%  TPN12%  Renal Disease11%  FHx10%

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%

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.

RSM Oct 2007 Childhood VTE – Outcomes OutcomeBPSUCanadaDPSU All cause Mortality 9%9.5%17% Direct Mortality 1.5%2.2%2%

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.

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

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

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)

RSM Oct 2007 CVL Related Thrombosis. CVLTE IncidenceOdds ratiop-value SC Vein44% ( ) Jugular Vein 20% Percutaneous47% ( ) Cut-down20% SCV/Percutaneous.54% ( ) TOTAL 33% (28/85) (Male, Blood 2002)

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

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

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”

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

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.

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.