RCH logo

Blood Transfusion

Neonatal transfusions

  • 1. Purpose and scope 

    Neonates, particularly those premature will commonly receive blood transfusions. Approximately 40% of low-birth-weight neonates and up to 90% of ELBW neonates will receive a red cell transfusion during their admission (Villeneuve, 2021).

    The purpose of this document is to provide guidance that ensures blood product prescription and transfusion thresholds are consistent with the current evidence and international guidance at The Royal Children’s Hospital (RCH).

    Neonatal transfusion should be undertaken with consideration to the guideline below and in conjunction with the RCH Blood transfusion – fresh blood products procedure. 

    2. Definitions 

    Term/Abbreviation Explanation
    CPAPContinuous positive airway pressure
    DICDisseminated intravascular coagulation  
    FBC Full blood count
    FFP Fresh frozen plasma
    Hb Haemoglobin
    ICHIntracranial hemorrhage
    NAIT Neonatal alloimmune thrombocytopenia 
    NEC Necrotising enterocolitis 
    PPV Positive pressure ventilation
    RBC Red blood cells

    3. Guideline 

    3.1 Red blood cells (RBC) 

    RBC transfusion thresholds 

    Haemoglobin (Hb) concentration declines in all neonates (term and preterm) within the first few months of life and reaches a nadir between week 6 and week 12 in term neonates. This nadir occurs earlier and is lower in preterm and low birth weight neonates. Anaemia of prematurity in preterm neonates is exacerbated by iatrogenic blood sampling and medical comorbidities.

    Randomised controlled trial evidence from the Transfusion of Prematures (TOP) trial and Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes (ETTNO) trial have demonstrated that red cell transfusions delivered at more restrictive thresholds are safe and associated with reduced exposure to red cell transfusion.

    The following table describes the Hb and transfusion threshold guidance for preterm (and *term) neonates at RCH. (See RCH Blood Product use in the Newborn Intensive Care Unit – Butterfly ward for further information).

    Table 1. 

    Hb red cell transfusion thresholds in preterm (and *term) neonate guidance

     

     Hb (g/L) 

    Critical threshold

    Hb (g/L)

    Non-critical threshold
     First 24 hours 110 100
     1 - 7 days 110 100
     8 - 14 days 100 85
     >15 days 85 70

    * Trial evidence is primarily from pre-term neonates, the evidence for term neonates is less clear, but the same thresholds are recommended.

    Critical threshold 

    Respiratory support (PPV, CPAP, high flow nasal cannula with FiO2 > 0.35 for greater than 12 hours in 24-hour period, supplemental O2 ≥ 1L/min), > 6 apnoeas requiring intervention per 24 hours, active NEC or sepsis requiring inotropic support, selected cardiac patients. 

    Non-critical threshold

    No respiratory support, well, no haemolysing or bleeding.

    Samples:

    Hb measured from a large artery, or veins tend to be lower than free flowing capillary samples. In general, a Hb result from an FBC is preferable to a Hb from blood gas. See Pre-transfusion testing for specific neonatal pre-transfusion sample information. 

    RBC dosing

    The typical neonatal red cell transfusion volume is 10 – 20ml/kg. The upper end of the range applies to severe anaemia, ongoing bleeding or haemolysis. Dosing should consider the weight of the neonate and, if available, the size of the pedi pack. 

    RBC components 

    Australian Red Cross Lifeblood (Lifeblood) manufacturer paediatric specific red cells called (Pedi packs). These are manufactured from an adult sized leucocyte-depleted unit which is divided into four packs of equal volume. Pedi packs assist with reducing donor exposure for neonates requiring transfusions and minimising wastage. Pedi packs may be requested from Lifeblood.

    RBC pedi pack specifications

    • Group O 
    • RhD positive or RhD negative

    Paediatric red cells may be irradiated at any time up to 14 days of collection. 

    Lifeblood typical RBC Pedi pack unit (2024)
    Parameter Mean ± 1SD Specification
    Volume (mL) 60 ± 4 25 – 100
    HCT (L/L) 0.62 ± 0.03 0.5 – 0.7

    In instances where pedi packs are not available, do not with-hold life-saving transfusions utilise adult RBC units. 

    Special neonatal RBC clinical indications 

    Haemolytic disease of the fetus and newborn (HDFN)

    		 Simple top up transfusions:
    • Group O and RhD compatible with mother and infant.
    • Red cells must be antigen negative for the corresponding maternal alloantibodies

    Exchange transfusions (see Exchange transfusion in NICU) 
    • Exchange transfusions may be performed to treat severe hyperbilirubinaemia and reduce this risk of kernicterus, by removing bilirubin, and in the case of HDFN, remove antibody coated red cells.
    • Lifeblood produces a specific red cell component for neonatal exchange transfusion that is:

            - Group O 

            - RhD negative, Kell negative

            - Red cell antigen negative for any maternal alloantibodies.

            - Fresh (< 5 days old)

            - Known haematocrit (0.60 L/L)

    • Red cells for exchange transfusion must be irradiated
    • Once irradiated, RBCs must be transfused within 24 hours.

    Large volume transfusion (e.g. exchange transfusion, ECLS or craniosynostosis surgery)

    Complications

    Neonates are at increased risk of hypothermia and metabolic complications following large volume red cell transfusions including electrolyte disturbances e.g., hypocalacaemia, hyperkalaemia and acid-base disturbances. 

    3.2 Platelets

    Platelet transfusion thresholds

    Neonates frequently receive platelet transfusions to treat (therapeutic) and to prevent bleeding when the platelet count is low or prior to some invasive procedures and surgery (see Table 2).

    The PLaNeT 2 study, a randomised clinical trial in pre-term neonates evaluated a platelet transfusion threshold of 25 x 109/L compared with a platelet transfusion threshold of 50 x 109/L. The study showed that in preterm infants with severe thrombocytopenia, those randomised to receive platelet transfusions at a threshold of 50 x 109/L had a significantly higher rate of death or major bleeding within 28 days of randomisation that those who received platelet transfusions at a threshold of 25 x 109/L (Curley et al, 2019). Sub-analysis by Fustulo-Gunnick et al. (2019) found that all neonates, even the sickest or those at most risk of major bleeding or death benefited. The following table describes neonatal platelet transfusion guidance at RCH. (See RCH Blood Product use in the Newborn Intensive Care Unit – Butterfly ward for further information).

    Table 2. 

    Suggested Neonatal platelet transfusion thresholds
    Platelet count (x109/L) Indication for platelet transfusion
    < 25
    • Neonates with no bleeding
    < 50
    • Neonates with bleeding
    • Neonates with coagulopathy/DIC
    • Neonates with NAIT (if previously affected sibling with NAIT and ICH)
    • Prior to surgery
    • Prior to lumbar puncture.
    < 100
    • Neonates with major bleeding (e.g. ICH)
    •  High risk surgery with significant bleeding risk:
       – Neurosurgery
       – Ophthalmologic surgery

    Platelet transfusion dosing

    The typical neonatal platelet transfusion volume is 10ml/kg (up to one pedi-pack).

    Dosing should consider the weight of the neonate and the size of the pedi-pack.

    Blood bank will supply the most appropriate unit with consideration to available stock and volume ordered. 

    Platelet components

    Lifeblood manufactures paediatric specific platelets that are leucocyte-depleted and suspended in platelet additive solution. An adult dose apheresis unit is divided into three packs of equal volume, to reduce neonatal donor exposure and minimise wastage.

    Lifeblood pedi pack platelets are:

    • Group O (group A or B may specifically be requested from Lifeblood on an individualised basis)
    • RhD negative or RhD positive
    • Typically CMV negative.
    • All platelets are irradiated by Lifeblood. 
    Lifeblood typical platelet pedi pack (2024)
    Parameter Mean ± 1 SD Specification
    Volume (mL) 55 ± 1 40 – 60
    Platelet count (x 109/unit) 72 ± 10 >50

    In instances where platelet pedi packs are unavailable, utilise appropriate adult sized platelet units. 

    3.3 Fresh Frozen Plasma (FFP) 

    There are significant differences between pre-term and term neonates, infants and children in the normal reference ranges of coagulation screening tests, such as Activated partial thromboplastin time (APTT) and prothrombin time (PT). Neonates have lower levels of most coagulation proteins, as part of their normal haemostatic development, which rarely corresponds to a significant spontaneous bleeding risk.

    Routine coagulation screening of all neonates may lead to inappropriate plasma transfusions; therefore, coagulation screening should be reserved for those neonates with bleeding, at high risk of bleeding e.g., NEC, DIC and sepsis. (New, 2016).

    There is no evidence that supports the transfusion of FFP to non-bleeding neonates with minor coagulation abnormalities.

    FFP may benefit neonates with clinically significant bleeding and prior to invasive procedures in those with significant coagulopathy. FFP may be ineffective in correcting an INR that is <2.5 (Karam, 2015).

    The INR correlates poorly with bleeding risk. Minor procedures may be performed with an INR of <2.0 (NBA, 2016). 

    Interpretation of coagulation tests in neonates

    Prolongations of the PT and/or APTT may indicate an underlying bleeding disorder and should be evaluated further with mixing studies and may require specific coagulation factor studies. Contact haematologist to provide guidance with further investigations.

    Interpretation of coagulation test in neonates
    Prolonged PT Full correction on mixing
    • Evaluation for vitamin K deficiency.
    • Treatment with vitamin K.
    • If persistent - evaluation for factor VII deficiency.
    Prolonged APTT Full correction on mixing
    • Male infant – evaluate for Haemophilia A (Factor VIII) and Haemophilia B (Factor IX)
    Prolonged APTT and PT Full correction on mixing
    • Evaluation for vitamin K deficiency and liver disease.
    • Treatment with vitamin K.
    • Common pathway factor deficiencies.


    FFP transfusion indications  

    The following table describes neonatal FFP transfusion guidance at RCH. (See RCH Blood Product use in the Newborn Intensive Care Unit – Butterfly ward for further information).

    Suggested Neonatal FFP transfusion guidance
    Non-bleeding neonates with coagulopathy
    • Do not routinely transfuse FFP
    Prevention of IVH associated with prematurity
    • Do not routinely transfuse FFP
    As a volume replacement
    • Do not routinely transfuse FFP
    Liver disease with coagulopathy and no bleeding
    • Do not routinely transfuse FFP
    Prior to invasive procedure
    • Balance the risk of bleeding associated with the procedure, the risk of complication from the procedure, the aetiology of the coagulopathy and whether alternate treatments may be appropriate.
    • The INR correlates poorly with bleeding risk.  
    • Minor procedures may be performed with INR <2.0s
    • FFP is largely ineffective at correcting INR <2.4s.
    Massive haemorrhage.
    • Provide balanced resuscitation with RBC, FFP,   platelets and cryoprecipitate to avoid haemodilution.
    • Aiming for an APTT/PT <1.5 x midpoint of normal range
    Clinically significant bleeding
    • Aiming for an APTT/PT <1.5 x midpoint of normal range
    Specific factor deficiencies (e.g., factor V deficiency) and bleeding
    • Where a specific factor concentrate is not available.
    Purpura fulminans secondary to homozygous protein C or S deficiency
    • Plasma transfusion is the treatment for protein S deficiency. Plasma transfusion should be administered until protein C concentrate is able to be obtained.
    Congenital TTP (Thrombotic, thrombocytopenic purpura)
    • Plasma exchange (simple transfusion may be performed until plasma exchange can commence).

    Paediatric FFP specifications

    Clinical FFP from a single unit of whole blood is divided into 4 equal volume pedi packs, with the purpose of reducing exposure and reducing component wastage.

    Typically manufactured as group AB.

    Lifeblood typical FFP Pedi pack (2024)
    Parameter Mean ± 1 SD Specification
    Volume (mL) 69 ± 4 60 - 80

    In instances where FFP pedi packs are unavailable adult-sized FFP should be utilised. 

    FFP dosing 

    The typical neonatal FFP transfusion volume is 10-20ml/kg. Dosing should consider the weight of the neonate and the size of the FFP pedi pack. 

    3.4 Cryoprecipitate 

    Fibrinogen is an essential coagulation factor for haemostasis and hypofibrinogenaemia is a significant risk factor for bleeding in neonates and children. Nevertheless, there are age-dependent differences in fibrinogen levels and fibrinolysis between neonates and older children and appropriate reference ranges should be utilised.

    Cryoprecipitate may be used to provide fibrinogen replacement and treat acquired hypofibrinogenaemia, in the contexts of bleeding, massive haemorrhage and prior to invasive procedures.

    Cryoprecipitate transfusion indications

    The following table describes neonatal cryoprecipitate transfusion guidance at RCH. (See RCH Blood Product use in the Newborn Intensive Care Unit – Butterfly ward for further information).

    Suggested Neonatal cryoprecipitate transfusion guidance
    Non-bleeding neonates with hypofibrinogenaemia
    • Do not routinely transfuse
    Liver disease with hypofibrinogenaemia and no bleeding
    • Do not routinely transfuse
    Prior to invasive procedures with a significant risk of bleeding or at a critical site (neurosurgery or eye surgery)
    • Consider cryoprecipitate when fibrinogen <1.0g/L
    Acute DIC and hypofibrinogenaemia and significant bleeding
    • Consider cryoprecipitate when fibrinogen <1.0g/L
    Acquired fibrinogen deficiency with minor bleeding
    • Consider cryoprecipitate when fibrinogen <1.0g/L
    Active bleeding (e.g. intraoperative or post-operative surgical bleeding)
    • Consider cryoprecipitate when fibrinogen <1.5g/L
    Prior to invasive procedures with a significant risk of bleeding or at a critical site (neurosurgery or eye surgery)
    • Consider cryoprecipitate when fibrinogen <1.5g/L
    Massive transfusion
    • Aim fibrinogen levels >1.5g/L

    Cryoprecipitate dosing 

    The typical neonatal cryoprecipitate transfusion volume is 5 -10ml/kg. Dosing should consider the weight of the neonate and the typical volume of the cryoprecipitate unit (37mls).

    Cryoprecipitate specifications

    Cryoprecipitate is prepared by thawing whole blood-derived FFP, recovering and re-freezing the cold-insoluble precipitate.

    Available in all ABO groups. 

    Lifeblood typical cryoprecipitate unit (2024)
    Parameter Mean ± 1 SD Specification
    Volume (mL) 37 ± 2 30 – 40
    Fibrinogen (mg/unit) 372 ± 114 ≥ 140
    FVIII (IU/unit) 152 ± 40 ≥ 70

    3.5 References 

    Curley A, Stanworth SJ, Willoughby K, Fustolo-Gunnink SF, et al. PlaNeT2 MATISSE Collaborators. Randomized Trial of Platelet-Transfusion Thresholds in Neonates. N Engl J Med. 2019;380:242-251.

    Franz AR, Engel C, Bassler D, et al.; ETTNO Investigators. Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Neonates: The ETTNO Randomized Clinical Trial. JAMA. 2020;324:560-570.

    Fustolo-Gunnink SF, Fijnvandraat K, van Klaveren D, Stanworth SJ, Curley A, et al. PlaNeT2 and MATISSE collaborators. Preterm neonates benefit from low prophylactic platelet transfusion threshold despite varying risk of bleeding or death. Blood. 2019;134:2354-2360.

    Karam O, Demaret P, Shefler A, Leteurtre S, Spinella PC, Stanworth SJ, Tucci M; Canadian Critical Care Trials Group (CCCTG); Pediatric Acute Lung Injury and Sepsis Investigators (PALISI); BloodNet; PlasmaTV Investigators. Indications and Effects of Plasma Transfusions in Critically Ill Children. Am J Respir Crit Care Med. 2015 Jun 15;191(12):1395-402. doi: 10.1164/rccm.201503-0450OC. PMID: 25859890. 

    Kirpalani H, Bell EF, Hintz SR, et al. NICHD Neonatal Research Network. Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Neonates. N Engl J Med. 2020;383:2639-2651.

    National Blood Authority (NBA) (2016). Patient Blood Management Guidelines: Module 6 – Neonatal and Paediatrics, NBA, Canberra, Australia.
    http://www.blood.gov.au/pbm-module-6 (http://www.blood.gov.au/pbm-module-6) 

    New HV, Berryman J, Bolton-Maggs PH, Cantwell C, Chalmers EA, Davies T, Gottstein R, Kelleher A, Kumar S, Morley SL, Stanworth SJ; British Committee for Standards in Haematology. Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol. 2016 Dec;175(5):784-828. doi: 10.1111/bjh.14233. Epub 2016 Nov 11. PMID: 27861734.

    Villeneuve, A, Arsenault, V, Lacroix, J and Tucci, M. Neonatal red blood cell transfusion. Vox Sang, 2021;116: 366-378

    Document authorship and review details
    Authorship Dr Gemma Crighton, Anne Kinmonth, Dr Helen Savoia
    Date first introduced ----
    Date of last review 7/03/2025
    Date of next review 24/09/2027
    Details of changes New document as of 24/09/2024