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Why PLANET-2 needs to succeed? Simon Stanworth Anna Curley.
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Transcript of Why PLANET-2 needs to succeed? Simon Stanworth Anna Curley.
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
Evidence-based focused review of platelet transfusions for critically ill patients with thrombocytopenia
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.
2. Common clinical problem
• Thrombocytopenia common, platelet transfusions still only main therapy
• Thrombopoietin analogues
3.
4. We should be learning lessons from other clinical groups/ settings?
1. The leukaemia population – no prophylaxis
2. TOPPS trial.
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
PP
ooppuullaattiioonn
Group 1
Group 2
HaemostaticOutcomes
Test: no-prophylaxis
Standard: prophylactic platelets at < 10x109/L
TOPPs: design
Recording bleeding
Grading 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
Subgroups – TOPPS Results: Primary Outcome
WHO grade 2-4 bleeding: no-prophylaxis: 50% (151/300) prophylaxis: 43% (128/298)
Predominant bleeding was grade 2
Learning about outcomes - bleeding
Next steps• Individualising use of platelet transfusions - subgroups• Risk factors
Rates of WHO grade 2-4 bleeding
Prophylaxis No Prophylaxis
AutologousHSCT
95/210(45%)
99/210(47%)
‘Other’: chemotherapy/ allogeneic HSCT
33/90(38%)
52/90(58%)
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
5.Platelet count poor predictor of bleeding risk
Morning platelet count and bleeding risk
Dose of prophylactic platelet transfusions and prevention of hemorrhage. Slichter et al. NEJM 2010;362:600-613
Bleeding the Following DayUnadjusted Odds Ratios (OR)
Odds Ratios and 95% Confidence Intervals
10.20 20.80.60.4 1.81.61.41.2
Total Platelet Count
Absolute Immature Platelet Number
Immature Platelet Fraction
P = 0.030
P = 0.008
P = 0.346
OR 0.60, 95% CI 0.41 to 0.88
OR 0.97, 95% CI 0.90 to 1.03
OR 0.98, 95% CI 0.97 to 1.00
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
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
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
7. Other potential side effects Necrotising enterocolitis
Retrospective analysis of neonates with NEC Results suggested platelet transfusions in
thrombocytopenic infants with NEC associated with greater morbidity
Kenton et al, J Perinatol. 2005;25:173-7
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.
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.
Because the public want research
The Planet-2 babies
The Planet two team
• TSC
• TMG
• CTU
• PIs
• Research nurses
• IDMC