Blood%20Transfusion%20in%20the%20Newborn

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An Evidence-Based Approach to Transfusion of the
Preterm Infant
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Disclosure

• I am on the speakers bureau for
• Ikari
• and
• Fisher Paykell

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Anemia of Prematurity

• 1. ANEMIA
• Definitions
• Clinical burden and effects
• Risk benefit ratio
• 2. REDUCING TRANSFUSION
• Placental transfusion
• Minimizing iatrogenic anemia
• Erythropoietin
• 3. WHAT HEMOGLOBIN TRIGGERS TO USE?
• Randomized Trial Data

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Hemoglobin and reticulocytes during first year of
life
Rapid developmental changes and complex
interactions for oxygen delivery (prevent)
developing clear cut criteria for transfusion.
Consequently clinical practices vary widely.
Lundstrom 1977 Saarnen and Siimes 1978 Cited
by Dallman PR 1981
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International survey of transfusion practices for
extremely premature infants. Guillén U Sem
Perinatol 201236244
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Risk benefit ratio of transfusions

• Higher hemoglobin may improve
• oxygen transport
• cardiac output
• weight gain
• apnea
• BUT may increase
• infections - donor related
• iron stores
• necrotising enterocolitis
• children adults - death rates
• complications from old blood

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Pre Tx 97-113 g/l
Pre Tx 97-113 g/l
Pre Tx 113-129 g/l
Pre Tx Hgblt97
Pre Tx Hgblt97
Pre Tx 113-129 g/l
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(J Pediatr 2014164475-80).
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Intra-hospital death to day 28 in 1077
infants with BW lt 1500 g
Transfused
Non-Transfused
Red Blood cell transfusions are independently
associated with intra-hospital mortality in VLBW
J Pediatrics 2011 159 371
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Do transfusions cause NEC? Kirpalani H, Zupancic
JA. Sem Perinatol 2012 36269 Whyte R, Kirpalani
H. Low vs high haemoglobin threshold for blood
transfusion in very low birth weight infants.
Cochrane Database Syst Rev. 2011CD000512
RCT Data
More NEC with restrictive transfusions
Favours Restrictive
Favours Liberal
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Do transfusions cause NEC? Kirpalani H,
Zupancic JA. Sem Perinatol 2012 36269
More NEC with liberal transfusions
Observational Studies
Favours Liberal
Favours Restrictive
OR of 7.5 is implausibly high
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Anemia of Prematurity

• 1. ANEMIA
• Definitions
• Clinical burden and effects
• Risk benefit ratio
• 2. REDUCING TRANSFUSION
• Placental transfusion
• Minimizing iatrogenic anemia
• Erythropoietin
• 3. WHAT HEMOGLOBIN TRIGGERS TO USE?
• Randomized Trial Data

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Effects of placental transfusion in ELBW long
and short-term outcomes Ghavam
S, Batra D, Mercer J, Kugelman A, Hosono S, Oh W,
Rabe H, Kirpalani H. Transfusion. 2014541192
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Phlebotomy overdraw in the neonatal intensive
care nursery. Lin JC, et al Pediatrics.
2000106(2) .
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Early Erythropoietin. Ohlsson A, Aher SM.
Cochrane 2014 4CD004863.
OUTCOMETransfusions ROP gt
Stage 3
614 Infants
862 Infants
RR 1.48 (1.02, 2.13)
RR 0.79 (0.73, 0.84)
Favours EPO Control
Favours EPO Control
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Anemia of Prematurity
1. ANEMIA - Definitions - Clinical burden
and effects - Risk benefit ratio 2.
REDUCING TRANSFUSION - Placental
Transfusion - Minimizing iatrogenic anemia -
Erythropoietin 3. WHAT HEMOGLOBIN TRIGGERS
TO USE? - Randomized Trial Data
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Comparison of Trial Design
Iowa Trial Iowa Trial PINT Trial PINT Trial
Restrictive Liberal Restrictive Liberal
Participating centers 1 1 10 10
No. of subjects 100 100 451 451
Treatment allocation Randomized Randomized Randomized Randomized
Stratification Birth weight Birth weight Birth weight, center Birth weight, center
Mean BW (g) 954 958 771 769
Mean GA (wk) 28 28 26 26

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Population lt32 wks GA
Intervention Liberal Hgb Tx
Comparison Restrictive Hgb Tx
Outcomes No. of RBC Tx Time frame
36 wks PMA
PICOT Iowa
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PRIMARY OUTCOME IOWA Number of Transfusions
High Hgb
Low Hgb
5.2 4.5
3.3 2.9
p 0.025
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ADDITIONAL OUTCOMES IN IOWA STUDY
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J Pediatr 2006149 301
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Population lt1000 g BW
Intervention Liberal Hgb Tx
Comparison Restrictive Hgb Tx Outcomes
Intact Survival Time frame 36 wks PMA
PICOT PINT
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Inclusions

• lt 1000 g BW
• lt 48 hours age
• lt 31 wks GA

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TRANSFUSION THRESHOLDS
PINT
Respiratory support
Yes No
Age Week one Week two Week three
High Low High Low
135 115 120 100 100 85
120 100 100 85 85 75
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PRIMARY OUTCOME PINT Death, BPD, severe ROP,
Brain Injury
High Hgb
Low Hgb
165/223 (74)
159/228 (70)
OR 1.3 95 CI 0.8-2.0 p 0.26
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PINT-Outcome Study (PINT-OS)
Primary Outcome a-priori components
0.1
OR
1
10
100
1.45 (0.94, 2.21) 1.18 (0.72,1.93) 1.32 (0.53,
3.27) 1.74 (0.98, 3.11) 2.16 (0.19, 24.1) 1.45
(0.32, 6.58)
Composite
p0.09
Death
Cerebral Palsy
p0.06
Cognitive Delay lt70
Blindness
Deafness
Favors Low Favors High
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PINT-Outcome Study (PINT-OS)
Post-Hoc Secondary Analysis
0.1
OR
1
10
100

1.71 1.12, 2.61
1.18 0.72 , 1.93
1.32 0.53 , 3.27
1.81 1.12,2.93
2.16 0.19 , 24.1
1.45 0.32 , 6.58
Composite
p0.013
Death
Cerebral Palsy
Cognitive Delay lt85
p0.016
Blindness
Deafness
Favors Low Favors High
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RCT era Risk benefit ratio of transfusions

• Higher hemoglobin may improve
• oxygen transport
• cardiac output
• weight gain - Not true
• apnea - Not true
• NEC ?
• Neurocognitive outcomes ?
• BUT may increase or unknown
• Infections - donor related
• iron stores
• death rates - unlikely

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WHEN SHOULD WE TRANSFUSE?
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Transfusions For Prematures (TOP) Does a
Liberal Red Blood Cell Transfusion Strategy
Improve Neurologically-Intact Survival
of ELBW Infants as Compared to a
Restrictive Strategy? Clinicaltrials.gov
NCT01702805
NICHD NEONATAL RESEARCH NETWORK
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CONCLUSIONS

• 1. Low thresholds of PINT and Iowa studies were
  comparable
• 2. It is reasonable to maintain infants above
  these lower thresholds
• 3. The high threshold was higher in Iowa
  than in PINT
• 4. The benefit of higher thresholds remains
  uncertain

16th Century dissection