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Blood products - red cell transfusion in the neonate

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Blood components available for red cell transfusion of neonates

New Zealand Blood Service currently provides two types of red cell components for neonatal use.

  • Whole blood plasma reduced - used for exchange transfusion and massive transfusion episodes (> 1 blood volume in 24 hours)
  • Red cells resuspended - used for top up transfusion of neonates (10 - 20ml/kg)

A detailed datasheet on these components can be accessed on the New Zealand Blood Service website (www.nzblood.co.nz). See also transfusion handbook 2016.

All blood components provided by NZBS are leucodepleted at source and CMV negative (see special considerations below). Statistical process control is used to ensure that greater than 99% of components will have a level of <5 x 106 WBC per unit (95% confidence). 

Common causes of neonatal anaemia

  • Preterm delivery before establishment of normal red cell and iron stores in last trimester
  • Blood loss for Laboratory testing
  • Expansion of blood volume with growth
  • Physiological cessation of red cell synthesis in the first 6 weeks after birth

Although these factors combine to result in the 'normal' fall in haemoglobin concentration in the first 6-9 weeks after birth, this is accompanied by improved oxygen unloading capacity as 2,3-DPG levels rise, so that tissue oxygen delivery may improve despite reduced oxygen carrying capacity. Thus the possible benefits of transfusion need to be balanced against the known (and unknown) risks for each individual baby.

Indications for transfusion

  1. Shock due to blood loss.  If severe see the Massive Transfusion Guideline (Term baby estimated total blood volume is 80ml/kg and extremely preterm baby is 100ml/kg)
  2. Exchange transfusion for severe haemolytic anaemia - See Neonatal Jaundice Guideline
  3. Anaemia of Prematurity - Transfusion thresholds. There have been four clinical trials comparing higher vs lower haemoglobin thresholds for red blood cell transfusion. The largest of these was the multicentre PINT trial which enrolled infants <31 weeks and <1,000g1. A systematic review of these trials, including 614 infants shows no difference in neonatal morbidity and mortality and no difference in neurodevelopmental outcome at 18-21 months. Using a restrictive (lower) threshold results in a significant reduction in the number of transfusions given2. A lack of benefit for a higher threshold suggests we should be guided by lower haemoglobin thresholds. The table below is modified from the PINT trial and the Canadian Paediatric Society Guideline3.
    Table 1. Haemoglobin concentration g/L (haematocrit %)
      Respiratory Support No Respiratory Support
    < 7 days 115 (35) 100 (30)
    8-14 days 100 (30) 85 (25)
    > 15 days 85 (25) 75 (23)
    These thresholds are for guidance only and should be individualised considering the following factors:
    •  Severity of respiratory disease (and other condition)
    •  Any symptoms that might relate to anaemia e.g increasing apnoeas.
    •  The reticulocyte count (marker of RBC production).
    •  Any evidence of on-going blood loss or haemolysis (e.g. a rhesus baby who'd been managed with intra-uterine transfusions).
    •  Possible or proven sepsis
    •  Baby to have surgery - It remains uncertain what the optimal preoperative haemoglobin should be for neonates undergoing major surgery.
  4. Stable growing babies > 6 weeks old
    Transfuse only if haematocrit < 23 and symptomatic. Transfusion at this age will inhibit the normal onset of erythropoiesis and should usually be discussed with a Specialist. 

Reducing the need for Red Blood Cell (RBC) Transfusion

Delayed cord clamping

Waiting for 30 to 120 seconds before clamping the cord allows about 15 to 20 mls/kg of blood to move from the placenta to the baby. There is good evidence from trials to date that delayed cord clamping reduces the need for later blood transfusion and reduces the total number of transfusions needed.4 In the most recent meta-analysis (which includes the 2017 Australian Placental Transfusion Study, APTS) delayed cord clamping in preterm infants reduced the proportion of infants needing a blood transfusion by 10%.5

Erythropoetin

The use of exogenous erythropoetin (EPO) to reduce the need for transfusion in preterm infants has been the subject of many clinical trials. Systematic review of these trials shows that early (before 8 days of age) or late EPO reduces the need for one or more transfusions and the number of transfusions per baby however, the small reductions are likely to be of limited clinical importance.6,7 There is a non-significant trend to a higher rate of ROP with early EPO. There is little support for the routine use of EPO but it should be considered in cases where there is a need to minimise the risk of requiring a blood transfusion, e.g babies of Jehovah's Witnesses (see section below).

Special considerations when transfusing neonates

Cytomegalovirus Infection

  • Infants weighing less than 1500g, those with immunodeficiency, and stem cell transplant recipients, are at greatest risk of transfusion transmitted CMV disease. These infants should receive cellular blood components that are CMV antibody negative.
  • Cellular blood components produced for neonatal use by NZBS are normally CMV antibody negative. In certain specific settings this may not however be possible.
  • When CMV antibody negative components are not available then the transfusion of leucodepleted components is an acceptable alternative

Irradiation of Blood Components

  • Detailed Guidelines on irradiation of blood components produced by the Australian and New Zealand Society for Blood transfusion (ANZSBT) can be obtained on the NZBS website (www.nzblood.co.nz)
  • Irradiation is used to reduce the risk of Transfusion associated Graft versus Host disease (TA-GvHD).
  • Irradiated components are required for:
    • Infants with known or suspected immunodeficiency disorders
    • Infants who have received intrauterine transfusions
    • Infants transfused with directed donations (from family relatives)
    • Exchange transfusion where the requirement to irradiate will not unduly delay transfusion.

Routine irradiation of cellular blood components for neonates outside of the above is not required by current international guidelines.

Hyperkalemia

Potassium leaches out of red cells during liquid storage. The potassium level in donated blood therefore increases with age. Clinically this is not normally a problem since the potassium rapidly re-enters the red cells following transfusion. The rate of potassium leakage increases significantly in red cell components that have been irradiated.

In certain clinical settings however the increased potassium level may be important. In such settings fresh blood (less than 5 days old) should be used. This applies to:

  • Exchange transfusion
  • Massive transfusion during surgery or following blood loss
  • Infants with significant renal impairment

Prescribing of blood and blood products

The Doctor/NS-ANP:

  • Prescribes the quantity and rate of administration required for transfusion on the blood transfusion/IV fluid balance chart (CR5541)
  • Records the treatment plan in the baby's clinical record
  • Requests blood from the blood bank on NZBS requisition form (111F01802)
  • For infants who are under 1000g and less than 10 days old, or infants who are likely to need multiple transfusions within the first few weeks, order a multipack. This will provide 4 paediatric packs of red cells from a single donor, thereby reducing donor exposure.

The Nurse must be notified that the blood or blood product has been ordered.

Transfusion Volume

  • In general a dose of 15ml/kg can be expected to raise the haemoglobin concentration by about 20g/L
  • Small babies (<1500g) in the first week of life: 10-15ml/kg over 2h
  • Larger babies and older babies: 15-20ml/kg over 2h to maximise haemoglobin rise while minimising numbers of transfusions required.
  • There is no indication for routine furosemide. If there is risk for fluid overload consider giving 1mg/kg at the start of the transfusion8.

Ordering

Paediatric packs of blood are requested one at a time from the Blood Bank as required. Individual aliquots from one adult can be reserved for sequential transfusions to the same baby over the 35 day shelf life of the red cells. This reduces multiple donor exposure. Blood must not be used if out of chilling facility for more than 15 minutes during transport, or prior to infusion.

If blood is not required, the Blood Bank must be informed and blood returned to the Blood Bank immediately.

Fill in the NZ Blood  Request for Blood Bank Tests and Blood Components or Products form. You will also need to complete a  Blood Bank Issue Sheet form CC7029. 

Blood and blood products are sent to the unit by the chute.

Pre-Administration Checklist

  • The unit of blood/plasma must be checked by a Registered Nurse with a current IV certificate and checked by a RN or Enrolled Nurse, Registered Obstetric Nurse with current IV certificate
  • Informed consent must be obtained unless the situation is life threatening. Consent is documented on the Agreement for Treatment (CR0111) form and signed by parent. However verbal consent by a parent is acceptable provided it is documented in baby's chart, until written consent can be obtained.
  • Check maternal antibody status and baby's blood group if known
  • Baby's identity - the baby's identification band is checked against front sheet of clinical records
  • Swinging label is checked with baby identity and component issue form
  • Swinging label is checked with label on bag for donation number, donation group, expiry date and/or collection date to determine age of blood. MUST BE LESS THAN 35 DAYS OLD. To limit donor exposure, dedicated units may be available for small babies who will require up to eight transfusions in the first four weeks of life
  • Check blood is leukodepleted and CMV negative
  • The unit of blood/plasma/platelets is checked for abnormalities (visual inspection)
  • Check prescription order and amount to be given (blood transfusion/IV fluid balance chart)
  • If administering blood via a luered cannula, check patency of luer prior to ordering blood.
  • Administration of each paediatric pack should take no longer than 2 hours - no exceptions. If the amount of blood required must be given over 3 hours, a further pack of blood will need to be obtained from blood bank.
  • If a Guthrie Card (NBST) has not yet been taken, ensure this is done prior to the first RBC Transfusion.

Administration 

  • Blood and blood products, except Albumin, must be filtered through a blood filter giving set (in-line filter set B860 with non-needle spike (180-200 micron size). They must not be infused through a Pall filter (0.22 micron)
  • Blood products are normally given through a peripheral IV sited for this purpose. See the Starship Clinical Guideline on Central Venous Catheters for more information
  • No substance is to be added to blood or blood products
  • Ensure blood syringe is not left in contact with heat source (e.g. under radiant heater or in incubator)
  • If baby is charted furosemide give via the injection port, flushing with saline before and after
  • Rotate syringe periodically to prevent pooling of red cells.

Set-up for administering blood via Central Venous Catheter:

  • Blood and blood products are NOT administered by percutaneous long lines.   
  • Blood given via CVL-UVC is a sterile technique
  • When no other access is available blood and IVN are alternated for half-hour intervals flushing with 0.5ml of 0.9% NaCl (following orders from doctor/NS-ANP).
  • NB: Blood must be administered below the Pall Filter
  • The procedure is the same for a luered CVL except only x one 3 way tap in line is required

Monitoring and documentation

  1. All observations are recorded on the blood transfusion/IV Fluid Chart (pink chart CR5541)
  2. Before commencement of blood, baseline recordings of temperature, heart rate, respirations and blood pressure will be taken and then repeated 15 minutes after commencement of blood
  3. Temperature, heart rate and BP will be recorded every 30 minutes
  4. When checking the unit of blood, the swinging label is checked and signed by both Nurses
  5. Ensure that donation number (sticky label) is placed in the patients clinical record as proof of transfusion

Potential complications

Irradiated Blood

  • On request red cells, platelets and granulocytes can be irradiated at Blood Bank. This reduces the risk of graft versus host disease. 
  • There is a 24 hour shelf life as potassium levels rise in stored irradiated units of blood.

Graft Versus Host (GVH)

Is a complication of transfusions and is due to the transfused white cells (lymphocytes) being immunocompetent and recognising the host cells as foreign tissue.

Hyperviscosity

  • Hyperviscosity may occur in adults when the haemoglobin is greater than 180g/L or the haematocrit greater than 0.65.
  • Hyperviscosity may result in poor circulation, thrombosis, tachypnoea, hypoglycaemia, heart failure, small cerebral thrombosis. In the neonate the plasma protein concentration of blood is lower than in the adult and therefore normal whole blood viscosity is maintained, even with haemoglobins as high as 200g/L. However if a neonate is transfused with adult plasma or blood, one should aim for a haematocrit of the transfused blood to be no greater than 0.65 and a haemoglobin no greater than 160g/L in order to reduce the risk of hyperviscosity problems.

Haemolysis

Haemolysis is the disintegration of red blood cells. It can be caused by:

  • Infusing blood rapidly through small gauge needles and in rare exceptions when a percutaneous longline is used. 
  • Infusing through 0.22 micron filter. 
  • Overheating blood. 
  • Storage at incorrect temperature. 
  • Mixing blood with other drugs. 
  • Mixing glucose with blood in the giving set (glucose rapidly enters the red cells and water follows causing the red cells to swell and haemolyse). 
  • Mixing with sterile water.

Transfusion reactions

Type of reaction Symptoms and signs
Febrile 1. Pyrexia, rigors
Circulatory Overload  1. Increase in blood pressure, heart rate and respirations.
2. Pulmonary oedema, dyspnoea, increase in urinary output
Allergic 1. Urticaria, facial oedema, dyspnoea, hypotension
2. TRALI (Transfusion associated lung injury)
Haemolytic  1. Collapse with hypotension.
2. Shock, pyrexia, rigors, haemoglobinuria, haemoglobinaemia, oliguria, later uraemia. 
Infected Blood  1. Pyrexia, profound collapse and shock, pallor, dyspnoea, low blood pressure, rapid pulse.

Management of Transfusion Reactions

Follow the steps below to manage the baby's reaction to blood and blood products.

  1. STOP THE TRANSFUSION IMMEDIATELY.
  2. The Nurse contacts the Doctor/NS-ANP immediately the baby manifests any sign of reaction.
  3. Babies vital signs must be recorded and documented.
  4. Maintain patency of cannula using a new giving set and 0.9% sodium chloride.
  5. Check label and recipient ID information is correct.
  6. Send NZBS Notification and Investigation of Adverse Transfusion form and the blood product with IV giving set attached in a plastic bag to the Blood Bank immediately to allow investigation of the cause of the reaction.
  7. Notify Blood Bank by phone; discuss urgency of follow-up tests and further transfusion needs.
  8. Take a sample of baby's blood (from a different vein). Blood group serology and EDTA - in purple top tube - send to Blood Bank. FBC + serum biochemistry.
  9. Consider need for blood cultures if sepsis suspected. Blood gases if respiratory distress present. Urine check for haemoglobinuria. Coagulation screen if bleeding.
  10. Parents of baby are to be informed.

Transfusion Associated NEC (TANEC)

It is currently uncertain whether NEC developing within 48 hours of a blood transfusion is an association or causation. In a meta-analysis of observational studies Mohamed et al report a moderate risk of bias, studies do not address the fact there are many cases of NEC that are not associated with transfusion, and many transfusions happen in preterm neonates who are not linked to NEC within 48 hours.9 Another prospective observational study reported severe anaemia not transfusion was associated with NEC.10 Some authors have suggested withholding feeds around a transfusion may reduce the risk of TANEC, however the level of evidence is low.11 It is not our routine practice to withhold feeds during a transfusion. 

Risks of infection

Human Immunodeficiency Virus (HIV) In Australia and NZ approximately 1 million units of blood and blood products are transfused annually. Since 1985 when HIV screening commenced, no known cases of post transfusion HIV infection have been detected.
Hepatitis B Now very rare post transfusion.
Hepatitis C No acute cases of Hepatitis C post transfusion have been detected since HCV screening commenced in 1992.
Creutzfeldt-Jakob Disease (CJD) There are no clearly documented cases of CJD being passed on by blood products. However it remains a theoretical possibility. This may be markedly reduced with pre-storage filtering of blood.
Cytomegalovirus (CMV) Occasional cases occur but are relatively rare. Neonatal transfused red blood cells are leukodepleted and CMV antibody negative

In New Zealand, blood for transfusion is carefully screened prior to being issued by blood bank. However there is always a risk that in the future other infectious diseases may be discovered.

Jehovah's Witnesses

The ADHB provides information for staff about Jehovah's Witnesses including medical management, and hospital liaison committee member contact details - see here for more information

Jehovah's Witnesses have definite objections to blood transfusions. In the event that a transfusion is indicated for an infant, then the following is recommended:

  1. Make sure Consultant is aware
  2. Discuss need for transfusion with the parents
  3. Review non-blood medical alternatives and if possible treat patient without using allogeneic blood. Erythropoietin use should be considered on an individual basis
  4. Consider contacting Hospital Liaison Committee member - see ADHB intranet for details

If transfusion is urgent:

  1. Ask parents for consent. If consent is withheld, then a decision to go ahead with the transfusion must be made in consultation with senior members of the medical team and clearly documented in the clinical record.
  2. If further transfusions are likely to be needed, ADHB legal counsel should be contacted

For less urgent transfusions, or where the need for transfusion is anticipated:

  1. Ask parents for consent. If consent is withheld then contact ADHB legal counsel for further advice including seeking legal guardianship for the blood transfusion

Anticipated transfusion need can include unwell ELBW infants, babies < 26 weeks, anaemic VLBW infants, significant haemolytic disease, very sick term infants (although many of these would fit the urgent transfusion criteria). 

There is law within the Health Act 1956 (Section 126B) that protects medical practitioners from civil or criminal proceedings for administering blood transfusions without consent to any person under the age of 20 years as long as the judge is satisfied that:

  • The transfusion was (in the reasonable opinion of the person administering the transfusion) necessary to save life, or to prevent permanent injury or prolonged and avoidable pain and suffering; and
  • There were reasonable attempts to obtain consent, or it was impracticable to obtain consent given urgency; and
  • In all the circumstances, administering the transfusion is reasonable

Associated documents

  • Nursing and Midwifery Practice Manual Administration of Blood and Blood Products
  • Informed Consent
  • New Zealand Blood Service Northern Region The Transfusion Medicine Handbook 2016
  • Minimal Haemolysis in Blood co-infused with amino-acid and Dextrose Solutions in Vitro. RP Jankov and RND Roy, J.Paediatric Child Health (1997) 33.P250-252.
  • Small volume Red Blood Cell Transfusions for Neonatal Patients. Heather Hume and Harry Bard.
  • Transfusion Medicine Reviews Vol IX, No 3 July 1995.P187-199.

For further information call the New Zealand Blood Service - Northern Region and ask to speak to the Medical Officer.
Bloodbank will inform the caller as to who this is and advise of appropriate telephone number.

References

  1. Kirpalani H, Whyte RK, Andersen C et al. The premature infants in need of transfusion (PINT) study: A randomised, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr 2006;149:301-7.
  2.  Whyte R, Kirpalani H. Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD000512. DOI: 10.1002/14651858.CD000512.pub2.
  3. Fetus and Newborn Committee. Whyte RK, Jefferies AL; Canadian Paediatric Society Red blood cell transfusion in newborn infants. Position Statement. Paediatr Child Health 2014;19(4):213-17
  4. Rabe H, Diaz-Rossello JL, Duley L, Dowswell T. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD003248. DOI: 10.1002/14651858.CD003248.pub3.
  5. Fogarty M, Osborn DA, Askie L et al. Delayed versus early umbilical cord clamping for preterm infants: A systematic review and meta-analysis, Amer J Obst and Gynae. 2017; 218(1)1-18.doi:10.1016/j.ajog.2017.10.231.
  6. Ohlsson A, Aher SM. Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD004863. DOI: 10.1002/14651858.CD004863.pub4. 
  7. Aher SM, Ohlsson A. Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD004868. DOI: 10.1002/14651858.CD004868.pub4.
  8. Balegar V, Kumar K and Kluckow M. Furosemide for Packed Red Cell Transfusion in Preterm Infants: A Randomized Controlled Trial. J Pediatr 2011;159: 913 -8
  9. Mohamed A; Shah PS. Transfusion associated necrotizing enterocolitis: a meta-analysis of observational data. Pediatrics 2012;129:529-40, 
  10. Patel RM, Knezevic AShenvi N et al. Association of Red Blood Cell Transfusion, Anaemia and Necrotising Enterocolitis in Very Low-Birth-Weight Infants. JAMA 2016;315:889-97.
  11. Keir AK; Wilkinson D. Do feeding practices during transfusion influence the risk of developing necrotising enterocolitis in preterm infants? Archives of Disease in Childhood 2013;98(5):386-8.

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Document Control

  • Date last published: 03 July 2018
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years