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Why PLANET-2 needs to succeed?

Why PLANET-2 needs to succeed?. Simon Stanworth Anna Curley. 1. The trial question is still relevant?. (Still) no evidence base No recent informative literature/studies US study not funded.

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Why PLANET-2 needs to succeed?

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  1. Why PLANET-2 needs to succeed? Simon Stanworth Anna Curley

  2. 1. The trial question is still relevant? • (Still) no evidence base • No recent informative literature/studies • US study not funded

  3. Evidence-based focused review of platelet transfusions for critically ill patients with thrombocytopenia

  4. Neonatal studies Recommendation: For critically ill children with severe thrombocytopenia and no evidence of bleeding, there is insufficient evidence to recommend for or against platelet transfusion.

  5. 2. Common clinical problem • Thrombocytopenia common, platelet transfusions still only main therapy • Thrombopoietin analogues

  6. 3.

  7. 4. We should be learning lessons from other clinical groups/ settings? • The leukaemia population – no prophylaxis • TOPPS trial.

  8. TOPPS • Prophylactic platelet transfusion used as standard practice but no supporting evidence base • Randomised clinical trial of no prophylaxis vs. prophylaxis: Prophylactic platelet transfusions reduce bleeding (50% to 43%) • May not be effective in all patient subgroups e.g. autologous stem cell transplants. • Other strategies e.g. TXA review and proposals new trial

  9. TOPPs: design Test: no-prophylaxis P o p u l a t i o n Group 1 Haemostatic Outcomes Group 2 Standard: prophylactic platelets at < 10x109/L

  10. Recording bleedingGrading bleeding (WHO) in adult trials Grade 1 - mild Grade 2 - moderate (red cell transfusion not needed acutely) Grade 3 - severe (requiring red cell transfusion within 24 hours) Grade 4 - debilitating/ life-threatening

  11. Subgroups – TOPPS Results: Primary Outcome WHO grade 2-4 bleeding: no-prophylaxis: 50% (151/300) prophylaxis: 43% (128/298) Predominant bleeding was grade 2

  12. Learning about outcomes - bleeding

  13. Next steps • Individualising use of platelet transfusions - subgroups • Risk factors

  14. Protocol adherence & Data completeness • Most transfusions in both arms were given according to protocol: no-prophylaxis [89%; 450/504] vs. prophylaxis [91%; 810/894] • Assessments completed on 93% (8405/9030) and 97% (8733/8970) of days in the no-prophylaxis group & prophylaxis groups

  15. 5.Platelet count poor predictor of bleeding risk

  16. Morning platelet count and bleeding risk Dose of prophylactic platelet transfusions and prevention of hemorrhage. Slichter et al. NEJM 2010;362:600-613

  17. Bleeding the Following Day Unadjusted Odds Ratios (OR) P = 0.030 Total Platelet Count OR 0.98, 95% CI 0.97 to 1.00 P = 0.008 Absolute Immature Platelet Number OR 0.60, 95% CI 0.41 to 0.88 P = 0.346 Immature Platelet Fraction OR 0.97, 95% CI 0.90 to 1.03 1 0 0.2 0.8 1.2 2 0.4 1.6 1.8 0.6 1.4 Odds Ratios and 95% Confidence Intervals

  18. 6.The risks of platelet transfusion • Uncertainty in neonatal transfusion practice. • Biological product • Risks of blood transfusion. • Potential for important benefits to reduce bleeding in neonates, and long term developmental consequences. • Prioritisation – the need for studies in children

  19. Risks of platelet transfusions Haemovigilance data (UK) Compared findings for adults vs children/infants: extrapolated data from ‘Where does blood go?’, 2008 Incidence of adverse outcomes of blood transfusion (per 100,000 red cells issued) Adults 13 Children <18 yrs 18 Infants <12 mths 37 Stainsby et al, Br J Haematol 2008; 141:73-79

  20. Haemovigilance: errors and clinical events Reasons for increase in errors Under-reporting in neonatal population: immunological immaturity, masked by symptoms, or simply not recognised e.g. necrotising enterocolitis other complications, such as line-associated infections, problems with multiple cannulations or extravasations rarely reported

  21. 7. Other potential side effects Necrotising enterocolitis Kenton et al, J Perinatol. 2005;25:173-7 • Retrospective analysis of neonates with NEC • Results suggested platelet transfusions in thrombocytopenic infants with NEC associated with greater morbidity

  22. 8. Addressing other clinical uncertainties • Use of non-steroidal anti-inflammatory drugs • The baby with rapidly falling platelet counts • Use of blood components, platelets (or plasma) as a volume expander.

  23. 9. Strengthening haematology research • The benefits of collaboration • The importance of supportive care & transfusion for sick neonates – colloids/albumin • Baseline for new targeted research e.g. individualise use of platelet and other blood components, thrombopoietin.

  24. Because the public want research

  25. The Planet-2 babies

  26. The Planet two team • TSC • TMG • CTU • PIs • Research nurses • IDMC

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