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Transfusion

• Introduction
• When to transfuse
• Complications
• Investigation
• Management of Normovolaemic anaemia of prematurity
• Acute Blood Loss
• Areas of Uncertainty in Clinical Practice

Introduction

Red blood cell (RBC) transfusions in neonates are used to treat

•  hypovolaemic anaemic shock

•  normovolaemic anaemia of prematurity, secondary to

  • Delayed and reduced RBC production
  • Shortened RBC survival
  • Rapid postnatal growth
  • Iatrogenic loss from frequent blood sampling for laboratory monitoring
•   hyperbilirubinaemia (double volume exchange transfusion)

 

This topic concentrates predominantly on the second scenario.

When to transfuse

There are no simple clinical or laboratory indicators of necessity for blood transfusion.

As the consideration of transfusion includes the combination of oxygen carrying and delivery, it should be noted that oxygen delivery is primarily determined by

• cardiac output
• haemoglobin concentration
• haemoglobin oxygen saturation

Final oxygen delivery is further dependent on

• the oxygen diffusion gradient (determined in part by the haemoglobin oxygen affinity)
• the diffusion distance between the capillary and the cell
• cellular uptake mechanisms

The theoretical critical haemoglobin (Hb) or haematocrit (Hct) threshold level required to maintain tissue oxygenation will vary dependent on the form of hypoxaemia.

Historically, transfusion guidelines have been shown to reduce transfusion rates in very premature newborns without worsening outcome though care should be taken when interpreting these reports.

Two recent trials have examined haemoglobin transfusion thresholds in very premature newborns.

The randomised PINT (Premature Infants in Need of Transfusion) trial included 451 newborns <1000g birth weight who were less than 48 hours of age. The trial compared two different transfusion algorithms (liberal vs. restrictive) based on chronologic age, haemoglobin threshold and need for respiratory support.   The trial showed no difference in hospital mortality or survival with BPD or vision threatening ROP or brain injury on head ultrasound.   At two year follow up there was no significant difference in the composite outcome of death or cerebral palsy, cognitive delay, hearing loss or blindness.

The other large randomised trial included 100 newborns between 500 and 1300grams birth weight. This trial compared slightly different transfusion algorithms based on haematocrit thresholds that varied by need for respiratory support. These targets were also based on the spectrum of clinical practice at the time. This trial showed no difference to in-hospital survival, ROP, BPD, time in supplemental oxygen, apnoea requiring ventilation or growth.

Unfortunately, neither trial provides a definitive answer as to when to transfuse a premature newborn with normovolaemic anaemia of prematurity. Both trials show a non statistically significant trend towards an advantage in the liberal transfusion arm with no difference in blood donor exposure.

In summary

1. There is no good evidence to support the use of transfusion for weight gain, apnoea requiring ventilation or dependency on supplemental oxygen.
2. Despite these trials there remains uncertainty about the precise timing and basis for transfusion in the context of anaemia of prematurity.

Complications

There are many potential adverse effects of RBC transfusion. These include

• volume overload
• immunosensitisation
• graft versus host disease
• metabolic derangements (hyperkalaemia, hypocalacaemia)
• transmission of infection (cases per million donations)
  • HIV (0.79)
  • hepatitis C (4.27)
  • hepatitis B (2.71)
• transfusion related acute lung injury (TRALI)
• necrotising enterocolitis has occasionally occurred post transfusion

 

Therefore RBC transfusion should be avoided, or if necessary the risk minimised by

• using guidelines for RBC transfusion as these can significantly reduce the number and volume of RBC transfusions. Although based on good quality randomised trials these algorithms were derived from variations in clinical practice.
• reducing donor exposure by the use of Pedi packs
• using CMV negative blood. The UK Transfusion Services guidelines (2002) recommend using CMV negative transfusions in the first year of life. However, leucocyte depleted (<5x106/unit) products may
  significantly reduce the risk of CMV transmission. Fetuses, infants <1500grams, immunodeficient
  patients and stem cell transplant recipients are at greatest risk of CMV transmission. If CMV negative products are not available (60-70% of adults are CMV positive), leucocyte depleted products are an acceptable alternative.
• using leucocyte reduced blood using a leucocyte depletion filter
• using irradiated blood.  Red cells are irradiated for exchange transfusion, after intra-uterine transfusion, directed donation (1st or 2nd degree relative) or HLA matched donor or when infant has suspected or proven immunodeficiency. Red cells should be used within 24 hours of irradiation. It is the responsibility of the doctor ordering the transfusion to request irradiated red cells. There is no evidence that transfusion with directed donor blood is safer for neonates.

Australian and New Zealand Society of Blood Transfusion (ASBT) Protocol avoids the need for repeated crossmatching prior to transfusion in the first 4months of life (development of antibodies to red cell antigens is very uncommon in the first 4 months of life). Once an infant is on the ASBT protocol no further samples are required for pretransfusion testing and blood may be ordered by telephoning the blood bank. Infants are eligible for ASBT if they are less than 4 months, have pretransfusion ABO and RH(D) group performed, are DAT negative, have no atypical red cell antibodies and have 1 continuous admission (babies that are discharged and readmitted must requalify for ASBT).

Investigation

• Hb, Hct, reticulocyte count
• ABO and Rh grouping of baby and mother

Management of Normovolaemic anaemia of prematurity

Consideration should be given to following the liberal algorithm of the PINT study.

Note that this is an operational guideline only. Consideration should be given to non-algorithm compliant transfusion in the event of poor circulation, shock (of any form), surgery and coagulopathy.

 PINT liberal Haemoglobin threshold algorithm

Note that there is a difference in threshold dependent on the site of collection (central [arterial/ venous] vs. capillary).

 

	If requiring	respiratory support	If NOT requiring	respiratory support
	Capillary haemoglobin	Central haemoglobin	Capillary haemoglobin	Central haemoglobin
Days 0-7	135g/l or less	122g/l or less	120 g/l or less	109g/l or less
Days 8-14	120 g/lor less	109 g/l or less	109 g/l or less	90g/l or less
Days 15 to discharge	100 g/l or less	90 g/l or less	85 g/l or less	77 g/l or less

• Do not transfuse to replace blood removed for laboratory testing.

Parents must be informaed of the need to transfuse a stable infant.

The exact volume of transfusion is not precisely known. A volume of 20ml/kg of packed RBC over 4 hours would reflect current practice. Infants with critical circulatory status may require frusemide 1mg/kg mid-way through transfusion. Feeds do not need to be witheld routinely during transfusion.

Acute Blood Loss

Transfuse with whole blood or packed RBC 20 ml/kg or estimated volume of blood loss titrated to infants response to transfusion. This should be given over 30 minutes. In emergencies uncrossmatched O Rh negative blood may be transfused.

Areas of Uncertainty in Clinical Practice

The use of recombinant erythropoietin remains controversial. The reader is referred to the Cochrane review on the topic for thorough discussion. Erythropoietin and iron/folate therapy may be considered in exceptional circumstances such as religious opposition to transfusion.

 

References

Bell EF, et al. Randomized trial of liberal versus restiricive guidelines for red blood cell transfusions in preterm infants. Pediatrics 2005; 115: 1685-1691.

Ramasethu J, Luban LC. Red blood cell transfusions in the newborn. Semin Neonatol 1999;4:5-16

Fetus and Newborn Committee, Canadian Paediatric Society. Guidelines for transfusion of erythrocytes to neonates and premature infants. Can Med Assoc J 1992;147:1781-6

Franz AR. Pohlandt F. Red blood cell transfusions in very and extremely low birth weight infants under restrictive guidelines: is exogenous erythropoietin necessary? Arch Dis Child Fetal Neonatal Ed 2001; 84: F96-100

Hume H. Red blood cell transfusions for preterm infants: the role of evidence-based medicaine. Semin Perinatol 1997; 21: 8-19

MaierRF et al Changing practices of red blood cell transfusions in infants with birth weights less than 1000g. J Pediatr. 2000 Feb; 136(2): 220-4

Kirpalani H et al The premature Infants in Need of transfusion (PINT) study: a randomized, controllde trial of restricitve (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. JPediatr. 2006 Sep; 149(3): 301-307.

Paul D, Leef K, Locke R, Stefano J. Transfusion Volume in Infants with very Low Birth Weight: A Randominzed Trial of 10 versus 20mL/kg J Pediatr Hematol Oncol 2002; 24(1) 43-46

Other Reading/Web links

Ramasethu J, Luban LC. Red blood cell transfusions in the newborn. Semin Neonatol 1999;4:5-16

RPA Newborn Care

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