Transfusion Volume for Children with Severe and LifeThreatening Anaemia

Kathryn Maitland; Peter Olupot-Olupot; Sarah Kiguli; George chagaluka; Florence Aloroker; Robert Opoka; Ayub Mpoya; Charles Engoru; J Nteziyaremye; Macpherson mellewa; Pedro Rafael Saramago Goncalves; Elizabeth George; Diana M. Gibb; Sarah Walker

doi:10.1056/NEJMoa1900100

Transfusion Volume for Children with Severe and LifeThreatening Anaemia

Kathryn Maitland, Peter Olupot-Olupot, Sarah Kiguli, George chagaluka, Florence Aloroker, Robert Opoka, Ayub Mpoya, Charles Engoru, J Nteziyaremye, Macpherson mellewa, Pedro Rafael Saramago Goncalves, Elizabeth George, Diana M. Gibb, Sarah Walker

Centre for Health Economics

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Severe anaemia (haemoglobin<6g/dl) is a leading cause of hospital admission and mortality in children in sub-Saharan Africa. World Health Organization recommends 20mls/kg whole blood equivalent regardless of haemoglobin, which standard calculations suggest is insufficient for deficit-correction. Methods: The TRACT factorial open-label trial randomized Ugandan and Malawian children aged 2 months to 12 years with haemoglobin <6g/dl and severity signs to immediate transfusion with 20mls/kg vs 30mls/kg whole blood equivalent. Three other randomizations investigated triggered transfusion, post-discharge micronutrients and/or cotrimoxazole. The primary endpoint was 28-day mortality. Results: 3196 eligible children (median 37 months; 2050(64%) with malaria) were randomized to 30mls/kg (n=1598) or 20mls/kg (n=1598) transfusion and followed for 180-days (134(4%) lost-to-follow-up). 1592(99.7%) 30mls/kg vs 1596(99.7%) 20mls/kg started transfusion, both a median 1.2h from randomization. Mean(standard deviation) total blood transfused was 475(385) vs 353(348) mls respectively. Haemoglobin recovery was significantly faster and greater with 30mls/kg (p<0.001). 55(3%) 30mls/kg vs 72(5%) 20mls/kg children died before 28-days (hazard ratio[HR]=0.76 (95% CI 0.54-1.08) p=0.13), and 134(8%) vs 154(10%) respectively before 180-days (HR=0.86 (0.68-1.09) p=0.21). Nevertheless, this masked significant heterogeneity (p≤0.004) at both time-points for fever (>37.5C) at screening. 30mls/kg reduced mortality in the 1943(61%) children without fever (28-day HR=0.43 (0.27,0.69) p=0.001), but increased mortality in the 1253(39%) children with fever (HR=1.91 (1.04,3.49) p=0.04). There was no evidence of differences between groups in re-admissions (p=0.38), serious adverse events (p=0.58) nor in haemoglobin recovery at 180-days (p=0.10). Conclusions: Mortality could be reduced by transfusing 30mls/kg whole blood equivalent in children presenting with severe anaemia without fever.

Original language	English
Pages (from-to)	420-431
Number of pages	12
Journal	New England Journal of Medicine
Volume	381
DOIs	https://doi.org/10.1056/NEJMoa1900100
Publication status	Published - 1 Aug 2019

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Maitland, K., Olupot-Olupot, P., Kiguli, S., chagaluka, G., Aloroker, F., Opoka, R., Mpoya, A., Engoru, C., Nteziyaremye, J., mellewa, M., Saramago Goncalves, P. R., George, E., Gibb, D. M., & Walker, S. (2019). Transfusion Volume for Children with Severe and LifeThreatening Anaemia. New England Journal of Medicine , 381, 420-431. https://doi.org/10.1056/NEJMoa1900100

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title = "Transfusion Volume for Children with Severe and LifeThreatening Anaemia",

abstract = "Background: Severe anaemia (haemoglobin<6g/dl) is a leading cause of hospital admission and mortality in children in sub-Saharan Africa. World Health Organization recommends 20mls/kg whole blood equivalent regardless of haemoglobin, which standard calculations suggest is insufficient for deficit-correction. Methods: The TRACT factorial open-label trial randomized Ugandan and Malawian children aged 2 months to 12 years with haemoglobin <6g/dl and severity signs to immediate transfusion with 20mls/kg vs 30mls/kg whole blood equivalent. Three other randomizations investigated triggered transfusion, post-discharge micronutrients and/or cotrimoxazole. The primary endpoint was 28-day mortality. Results: 3196 eligible children (median 37 months; 2050(64%) with malaria) were randomized to 30mls/kg (n=1598) or 20mls/kg (n=1598) transfusion and followed for 180-days (134(4%) lost-to-follow-up). 1592(99.7%) 30mls/kg vs 1596(99.7%) 20mls/kg started transfusion, both a median 1.2h from randomization. Mean(standard deviation) total blood transfused was 475(385) vs 353(348) mls respectively. Haemoglobin recovery was significantly faster and greater with 30mls/kg (p<0.001). 55(3%) 30mls/kg vs 72(5%) 20mls/kg children died before 28-days (hazard ratio[HR]=0.76 (95% CI 0.54-1.08) p=0.13), and 134(8%) vs 154(10%) respectively before 180-days (HR=0.86 (0.68-1.09) p=0.21). Nevertheless, this masked significant heterogeneity (p≤0.004) at both time-points for fever (>37.5C) at screening. 30mls/kg reduced mortality in the 1943(61%) children without fever (28-day HR=0.43 (0.27,0.69) p=0.001), but increased mortality in the 1253(39%) children with fever (HR=1.91 (1.04,3.49) p=0.04). There was no evidence of differences between groups in re-admissions (p=0.38), serious adverse events (p=0.58) nor in haemoglobin recovery at 180-days (p=0.10). Conclusions: Mortality could be reduced by transfusing 30mls/kg whole blood equivalent in children presenting with severe anaemia without fever.",

author = "Kathryn Maitland and Peter Olupot-Olupot and Sarah Kiguli and George chagaluka and Florence Aloroker and Robert Opoka and Ayub Mpoya and Charles Engoru and J Nteziyaremye and Macpherson mellewa and {Saramago Goncalves}, {Pedro Rafael} and Elizabeth George and Gibb, {Diana M.} and Sarah Walker",

year = "2019",

month = aug,

day = "1",

doi = "10.1056/NEJMoa1900100",

language = "English",

volume = "381",

pages = "420--431",

journal = "New England Journal of Medicine ",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

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TY - JOUR

T1 - Transfusion Volume for Children with Severe and LifeThreatening Anaemia

AU - Maitland, Kathryn

AU - Olupot-Olupot, Peter

AU - Kiguli, Sarah

AU - chagaluka, George

AU - Aloroker, Florence

AU - Opoka, Robert

AU - Mpoya, Ayub

AU - Engoru, Charles

AU - Nteziyaremye, J

AU - mellewa, Macpherson

AU - Saramago Goncalves, Pedro Rafael

AU - George, Elizabeth

AU - Gibb, Diana M.

AU - Walker, Sarah

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background: Severe anaemia (haemoglobin<6g/dl) is a leading cause of hospital admission and mortality in children in sub-Saharan Africa. World Health Organization recommends 20mls/kg whole blood equivalent regardless of haemoglobin, which standard calculations suggest is insufficient for deficit-correction. Methods: The TRACT factorial open-label trial randomized Ugandan and Malawian children aged 2 months to 12 years with haemoglobin <6g/dl and severity signs to immediate transfusion with 20mls/kg vs 30mls/kg whole blood equivalent. Three other randomizations investigated triggered transfusion, post-discharge micronutrients and/or cotrimoxazole. The primary endpoint was 28-day mortality. Results: 3196 eligible children (median 37 months; 2050(64%) with malaria) were randomized to 30mls/kg (n=1598) or 20mls/kg (n=1598) transfusion and followed for 180-days (134(4%) lost-to-follow-up). 1592(99.7%) 30mls/kg vs 1596(99.7%) 20mls/kg started transfusion, both a median 1.2h from randomization. Mean(standard deviation) total blood transfused was 475(385) vs 353(348) mls respectively. Haemoglobin recovery was significantly faster and greater with 30mls/kg (p<0.001). 55(3%) 30mls/kg vs 72(5%) 20mls/kg children died before 28-days (hazard ratio[HR]=0.76 (95% CI 0.54-1.08) p=0.13), and 134(8%) vs 154(10%) respectively before 180-days (HR=0.86 (0.68-1.09) p=0.21). Nevertheless, this masked significant heterogeneity (p≤0.004) at both time-points for fever (>37.5C) at screening. 30mls/kg reduced mortality in the 1943(61%) children without fever (28-day HR=0.43 (0.27,0.69) p=0.001), but increased mortality in the 1253(39%) children with fever (HR=1.91 (1.04,3.49) p=0.04). There was no evidence of differences between groups in re-admissions (p=0.38), serious adverse events (p=0.58) nor in haemoglobin recovery at 180-days (p=0.10). Conclusions: Mortality could be reduced by transfusing 30mls/kg whole blood equivalent in children presenting with severe anaemia without fever.

AB - Background: Severe anaemia (haemoglobin<6g/dl) is a leading cause of hospital admission and mortality in children in sub-Saharan Africa. World Health Organization recommends 20mls/kg whole blood equivalent regardless of haemoglobin, which standard calculations suggest is insufficient for deficit-correction. Methods: The TRACT factorial open-label trial randomized Ugandan and Malawian children aged 2 months to 12 years with haemoglobin <6g/dl and severity signs to immediate transfusion with 20mls/kg vs 30mls/kg whole blood equivalent. Three other randomizations investigated triggered transfusion, post-discharge micronutrients and/or cotrimoxazole. The primary endpoint was 28-day mortality. Results: 3196 eligible children (median 37 months; 2050(64%) with malaria) were randomized to 30mls/kg (n=1598) or 20mls/kg (n=1598) transfusion and followed for 180-days (134(4%) lost-to-follow-up). 1592(99.7%) 30mls/kg vs 1596(99.7%) 20mls/kg started transfusion, both a median 1.2h from randomization. Mean(standard deviation) total blood transfused was 475(385) vs 353(348) mls respectively. Haemoglobin recovery was significantly faster and greater with 30mls/kg (p<0.001). 55(3%) 30mls/kg vs 72(5%) 20mls/kg children died before 28-days (hazard ratio[HR]=0.76 (95% CI 0.54-1.08) p=0.13), and 134(8%) vs 154(10%) respectively before 180-days (HR=0.86 (0.68-1.09) p=0.21). Nevertheless, this masked significant heterogeneity (p≤0.004) at both time-points for fever (>37.5C) at screening. 30mls/kg reduced mortality in the 1943(61%) children without fever (28-day HR=0.43 (0.27,0.69) p=0.001), but increased mortality in the 1253(39%) children with fever (HR=1.91 (1.04,3.49) p=0.04). There was no evidence of differences between groups in re-admissions (p=0.38), serious adverse events (p=0.58) nor in haemoglobin recovery at 180-days (p=0.10). Conclusions: Mortality could be reduced by transfusing 30mls/kg whole blood equivalent in children presenting with severe anaemia without fever.

U2 - 10.1056/NEJMoa1900100

DO - 10.1056/NEJMoa1900100

M3 - Article

SN - 0028-4793

VL - 381

SP - 420

EP - 431

JO - New England Journal of Medicine

JF - New England Journal of Medicine

ER -