Factorial design: 3950 children with severe anaemia Transfusion strategies Long-term management Blantyre Malawi Uganda TRansfusion and TReatment of severe Anaemia in African Children Trial

Pattern of usage of blood: demand UK Africa Largely elective-use Pre-planned and predictable ¾ ’s blood use: paediatric & pregnancy-related Largely emergency use Unpredictable Highly seasonal

Recommendations for Paediatric transfusion and concerns Give a transfusion (20mls/kg whole blood or 10mls/kg packed cells to all children with a Hb of ≤4 g/dl (profound anaemia) less severely anaemic children (Hb 4–6 g/dl) +features of severity Current recommendation developed by ‘blood safety’ committee of WHO (transfusion specialists) not paediatric guideline committee Designed to protect supplies of blood Not evidence based- but driven by necessity Evidence suggests that doctors usually ignore these One size fits all: leads to 30% under transfused (Kiguli BMC Med 2015)

Severe anaemia group (Hb < 5g/dl)* 48 hour mortality if received BTX within 8 hours =4% 48 hour mortality if DID NOT get BTX within 8 hours =54% Poor Tx guideline compliance:

Transfusion questions Which children should receive a transfusion? Current WHO guidelines have not been evaluated in clinical trials. We don’t know if giving blood to all children with Hb <6g/dl would help. How much blood should be given in a transfusion? A quarter of children receiving transfusions remain severely anaemic and up to one third get two or more blood transfusions during a single hospital admission. We don’t know if giving larger initial volumes of blood would help

Transfusion Strategies in TRACT Transfusions strategies are  30ml/kg whole blood or 15mls/kg packed cells (R1:30)  20ml/kg whole blood or 10mls/kg packed cells (R2:20)  No Transfusion (standard of care) Transfusion Strategy indicated here

And new terminology for most clinicians!! Whole blood Either delivered in the same bag or one or more satellite bags from the donor: closed system; no dilution); alternatively via a transfer bag (open system: no dilution) Median haematocrit for whole blood = 45-55% Packed cells (spun in centrifuge, plasma removed) Median haematocrit for packed cells ~55-60% (WHO considers this to be 70%); ‘Settled cells’ or red cell concentrate (settled whole blood by gravity, plasma removed) Median haematocrit 50-55%

Whole blood Viable for days Red cell concentrate from decantation Viable for days Packed cell Viable for 1 day only Red cell concentrate from centrifugation Viable for days WHO WHO indicates packed cells but these are only viable for one day!! Vast majority of red cell are concentrates ie LOWER haematocrit as SAGM addeed

Pre-trial audit

Packed cell?? Whole blood??

Early-trial audit

Blood pack type and haematocrit Median (IQR) haematocrit by supply method: no significant difference according to type of blood Number of packs with haematocrit information (%) Median (IQR) haematocrit of packs Whole blood (direct)79 (68%)61 (52, 77)~45 Whole blood (transfer bags)39 (67%)56 (47, 65)~45 Packed cells (spun)36 (43%)54 (49, 68) ~55-60 (WHO 70) Semi-packed cells (gravity)77 (96%)64 (53, 71)~50-60 *P-value for two sided t-test (unequal variance) comparing means in those with whole blood (direct) and packed cells (spun) is p=

Training and meetings Something about communication/strengthening improved labelling etc

2015 April re-audit Compare mean Hb and HCT after training on pack identification

SitePack typeNMean HCTMean Hb Haemocue Mean Hb CBC MulagoPacked cells spun MbaleRed cell concentrate (gravity) SorotiRed cell concentrate (gravity) SorotiWhole blood NOTE: The median haematocrit for whole blood should be 45-55% and for packed cells ~55-60% (WHO considers 70%); for semi-packed 50-55%.

Lessons learnt Strengthening of communication between regional BTS, hospital transfusion labs and clinicians on paediatric wards to ensure the quality control of blood issued for transfusion. Proper identification of blood packs is essential for continuous quality control As we wait for evidence from robust clinical trials on BT, clinicians should adhere to the current guidelines “Standard of care”.

Acknowledgements The TRACT study group BTS – Uganda and Malawi Hospitals involved