Transfusion in fetuses, neonates, older children (BSH 2016)
Definitions
Neonate – up to 28 days
Infant – 28 days to 1 year
Clinically significant bleeding = WHO bleeding grades 2-4 (of total range 1-4)
Blood Components - basic requirements
Red Cells - additional requirements
Platelets - additional requirements
FFP and Cryo - additional requirements
Granulocytes - additional requirements
Plasma components
Imported for all patients born after 1st jan 1996
Methylene Blue (MB) treatment results in 25-30% reduced factors VIII, XI, FGN and reduced thrombin generation. This is of uncertain clinical significance.
Solvent Detergent (SD) treatment results in reduced protein S, antitrypsin and antiplasmin and has been associated with thrombosis.
Neonates
Intrauterine transfusion (IUT) / Fetal Blood Sampling (FBS)
Continuous ultrasound, can be performed ages 16-35 weeks
Risks: 1-3% fetal death per procedure, up to 20% in hydrops fetalis
AE’s: miscarriage, preterm labour, fetal bradycardia, cord haematoma, vessel spasm, bleeding from puncture site.
QA – 2 specialists + minimum 15 procedures per year
Red cell IUT
Indications: HDN 2o to anti-D, -c or –k, or fetal parvovirus
Middle cerebral artery peak systolic velocities (MCA PSV) for non-invasive diagnosis
Transfuse aiming for Hct 0.45
Aim for delivery at 37-38 weeks
24 hours to prepare – in emergency irradiated red cell exchange units or irradiated paedipacks are acceptable.
Post-delivery Management
Monitor for several weeks, risk of haemolysis / bone marrow suppression in neonates that were transfused for HDN.
Anaemia beyond a few weeks usually result of passively acquired maternal antibodies (jaundice, haemolytic blood film).
Late anaemia follows transient suppression of neonatal erythropoiesis by transfusion.
Platelet IUT
Indication: Neonatal Alloimmune Thrombocytopenia (NAIT)
Almost all cases due to alloantibodies to HPA-1a (80-90%), HPA-5b and HPA-3a
Treat mother with steroids / IVIg in first instance to avoid IUT
Greatest risk at plt count <50
Transfuse more slowly than red cells due to risk of circulatory stasis / stroke
Neonatal Red Cell Transfusion
15ml/kg for non-bleeding neonates
Principles
Guidelines developed based on studies for VLBW pre-term babies (<1.5Kg)
90% of <28wk pre-term babies require transfusion, often iatrogenic anaemia
Neonatal blood volume is 80ml/kg
Physiology is poorly understood - e.g. transfusion is replacing HbF with adult HbA which has a different oxygen dissociation curve. ?Complications of prematurity such as retinopathy and bronchopulomnary dysplasia related to this.
Transfusion thresholds:
Restrictive non-inferior to liberal thresholds and so restrictive arguably the preferred strategy
Iowa 2005, PINT 2006, TOP 2020, ETTNO 2020, Plos One Meta-analysis 2021
Red cells
Indications: Surrogate markers of anaemia – poor growth, lethargy, apneic episodes
Risks: as for adults + necrotizing enterocolitis (NEC)
Use of paedipacks reduces donor exposure for multiply transfused neonates
Exchange blood transfusion (EBT)
Indications: rapidly rising bilirubin not response to phototherapy or IVIg. Or for severe anaemia.
Used in HDN to prevent bilirubin encephalopathy and removes antibody-coated red cells and excess bilirubin.
Other uses include other causes of neonatal hyperbilirubinaemia – e.g. G6PD def
Single blood volume EBT removes 75% of neonatal RBC’s, double vol up to 85-90%, and 50% of circulating bilirubin.
EPO
May reduce need for transfusion. Risk of retinopathy of prematurity (due to stimulated neovascularization).
Placental transfusion and delayed cord clamping (DCC)
Where baby does not need resuscitation, DCC of 1 minute increases Hb, reduces frequency of iron def at 2-6 months and reduced transfusion requirement.
Surgery and large volume transfusion (non-cardiac)
Definition – 80ml/kg in 24 hours or 50% of circulating volume in 3 hours
To avoid hyperkalaemia /hypothermia à red cells <5 days old, within 24 hours of irradiation, transfused through blood warmer.
Neonatal Platelet Transfusion
PLANET-2 2019 - Restrictive thresholds reduced death and major bleeding versus liberal strategy. Why? As with RBC an adult product is replacing neonatal cells. Platelets have many immune and inflammatory roles and interactions with neonatal transfusion poorly understood.
NICU’s often use plt count <25 as trigger for transfusion
NAIT – monitor with cranial USS for hemorrhage. No bleeding, Tx <25, bleeding aim for 50-100. IVIg alternative if HPA-1a/5b neg platelets do not increment. Resolves spontaneously 1-6 weeks after birth.
Neonatal FFP / Cryoprecipitate
Uncertainty around appropriate use of FFP prophylaxis
Studies show inconsistent benefit of coagulopathy screening and early plasma use to prevent intracranial bleeding. 1996 study showed no benefit (but neonates are younger now)
Normal values for PT/APTT poorly defined in neonates
‘Normal’ local population samples hard to attain + variation in analysers and reagents means difficult to interpret results. This most affects APTT.
PT raised by polycythaemia.
Neonatal purpura fulminans (PF)
Skin necrosis and DIC secondary to severe protein C or S deficiency
Early recognition and treat with FFP. Prot C concentrate available. No Prot S.
T-activation
Occurs in neonatal sepsis, particularly NEC and S.pneumoniae.
Neuroaminidase produced by infective organism strips sialic acid from red cell surface, exposing the T-cryptantigen.
Detectable by lectin panel.
Anti-T antibodies are naturally occurring IgM, developing in infancy.
Where haemolysis post-transfusion occurs and high suspicion this is due to anti-T, could consider:
Red cells in SAGM (little plasma present)
Low-titre anti-T FFP
Washed platelets in platelet suspension medium
Infants and Children
Calculate Vol. = (Desired Rise in Hb x weight(kg) x 4) / 10
Principles
50% of paediatric transfusion to non-neonates go to haem-onc patients
Other groups – cardiac surgery, PICU, ECMO
Children receiving regular transfusions should be vaccinated for Hep B
Those on chronic transfusions should have extended red cell phenotyping/genotyping, e.g. haemoglobinopathies, aplastic anaemia
Monitor growth – e.g. restrictive transfusion in thalassemia may impair it
Red cell transfusion
PICU
TRIPICU 2007 – restrictive threshold (70g/l) reduced blood use, no extra harm
Phlebotomy losses contribute to anaemia and increased blood requirement
Stem cell transplant / oncology
No specific guidance, current practice suggests 70-80g/l threshold is appropriate
?Tx for thalassemia - ?hypertransfuse to improve engraftment. Not been proven.
Surgery (non-cardiac)
Craniofacial, scoliosis and cardiac surgery cause greatest blood loss
Correct iron def pre-op
Tranexamic acid reduces blood loss – best dose and side effects not fully established
As for PICU, transfusion threshold of 70g/l
Consider cell salvage
Platelet Transfusion
Principles
No data on transfusion thresholds in haem-onc
Howard et al 2000 – 941 LP’s performed on children with plt <50 and without prophylactic plt transfusion found no bleeding events.
Survey of UK paed centers plt threshold prior to LP found variation of 10-80
FFP & Cryoprecipitate
Principles
Very little evidence of most current uses of FFP in infants and children
Should not be used to correct minor PT defects in non-bleeding pts prior to surgery
Suggested FGN threshold of 1.0g/l for transfusion
Major indications or cryoprecipitate in infants and children are DIC with bleeding,
bleeding following cardiac surgery and major haemorrhage.
Major Haemorrhage
Blood volume of children approx. 80ml/kg
Major haemorrhage = 80ml/kg in 24 hours, 40ml/kg in 3 hours or 2-3ml/kg/min
Management as for adults
Volume to transfuse = (Desired Hb – Actual Hb) x Weight x Factor / 10
Factor can be between 3-5, often 4 is used
4ml/kg is approx. equal to a one unit transfusion in an adult, raising Hb by 10g/l
Maximum 20ml/kg