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Pediatric
Transfusion
Risks and GuidelinesRisks and GuidelinesJed B. Gorlin, MD
Memorial Blood Center Minnesota
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Trends in NeonatalTrends in Neonatal
TransfusionTransfusion
Transfusionpractices have
become moreconservative.
Survival continuesto improve despite
less bloodtransfused!
Extreme premies(
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PediatricTransfusion:PediatricTransfusion:Risks and GuidelinesRisks and Guidelines
Review of overall risks of transfusionGuidelines for Pediatric Transfusion
Red Cell
PlateletPlasma
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Risks ofTransfusionRisks ofTransfusion
Infectious Risks
Viral
Bacterial
Protozoa
Ricketsia
Other
?Prion
Non-infectious risks
Transfusion Reaction
Metabolic
Cardiac Overload
Dilutional Coagulopathy
TAGVHD
Alloimmunization
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Transfusion SafetyTransfusion Safety
Product Safety
DonorRecruitment
Donor historyscreening
Donor Testing
Manufacturing cGMP
Transfusion Safety Patient blood sample
Med indication for Tx. Special Tx needs
Select right unit
Issue to floor
administration
monitoring & evaluationof reaction
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Current Risks SummaryCurrent Risks Summary
(NAT)(NAT)
HIV, HCV 1 in 1,000,000
Bacteria 1 in 1-10,000
Mis-transfusion 1 in 500-16,000
Lung injury 1 in 5000
TAGVHD 1 in 10,000?
Cardiac 1 in 100-1,000Metabolic rxn neonate 1 in 10-100
Undertransfusion 1 in 50-1000
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NonNon--Infectious RisksInfectious Risks
Transfusion Reactions
Metabolic complicationsDilutional coagulopathy
Cardiac Overload
TAGVHD
Alloimmunization-RBC, platelets
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Transfusion ReactionsTransfusion Reactions
Hemolytic
Acute hemolytic (typical ABO incompatibility)
Delayed (antibodies to minor red cell antigens)
Febrile
Allergic
Severe: Anaphylaxis, Shock
Moderate: Extensive Hives, itching
Mild: Few hives
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WHOLE BLOOD ABO AND RH
COMPATIBILITY
DONOR
RECIPIENT A B O AB Rh
Positive
Rh
Negative
A y
B y
O y
AB y
Rh Positive y y
Rh Negative y
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PACKED RBC ABO AND RH
COMPATIBILITY
DONOR
RECIPIENT A B O AB RhPositive
RhNegative
A y y
B y y
O y
AB y y y y
Rh Positive y y
Rh Negative y
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CMVatrisk guidelineCMVatrisk guideline
CMV Ab - pregnant women/fetus
Premature infants (
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MetabolicComplicationsMetabolicComplications
Infants at particular risk
Hyperkalemia- K leaks out of cells as they age.Irradiation doubles rate of leak.
Hypothermia- Use blood warmer
Hemolysis
Storage: exposure to freezing or excessive heat
Hypo-osmotic: Only use compatible solutions Bacterial contamination may cause hemolysis
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Transfusion AssociatedTransfusion Associated
GraftGraft--Versus Host DiseaseVersus Host Disease
When donor lymphocytes attack the host
Host Immuncompetent
Host Overwhelmed (Premie)
Host Immune-competent but donor is HLAhomozygous for an HLA antigen that therecipient is heterozygous for. Most common
setting is related donor.
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AABB TAGVHD @ risk guideAABB TAGVHD @ risk guide
Irradiate cellular components to 2500(1500)
BMTX congenital immune deficiency
Neonates getting intrauterine, during or postexchange
Hodgkins lymphoma Directed donor/family member/HLA or X-
match
? Premie < 1200, other chemo (fludarabine,2CDA)
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NeonatalTx.NeonatalTx.-- TAGVHDTAGVHD
No apparent increased risk in full termnewborns
Low risk in premies. However,premature infants also represent one ofthe largest number of reports. Majority
represent related directed donors.Consensus (
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TransfusionTransfusion--related lungrelated lung
injuryinjury
Incidence ~1:5,000 but rarely reported inpediatric transfusion recipients
Pathogenesis: Donor anti-HLA and anti-PMNantibodies causing activation of hostleukocytes = pulmonary capillary trapping.
May be fatal
Donor is typically multiparous female
Usually Platelet or Plasma comp. RBC rare
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Alternatives to bloodAlternatives to blood
transfusiontransfusion
Lower transfusion triggers: What we havelearned from Jehovahs Witness patients
Autologous transfusion Beware overzealousdonation may cause iatrogenic anemia
Pharmacologic: Iron, Folate, Erythropoietin(see Neonatal issues)
Intraoperative hemodilution &blood salvage
Hemoglobin/Platelet substitutes
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Directed DonationsDirected Donations
Pros: Keeps patient,
parents andextended familyhappy.
May result in fewerdonor exposures
May encourageblood donation byindividuals who donot usually donate
Cons: No study shows that
directed donations aresafer and many showthat directed donor bloodis rejected at a greaterrate. (first time donationrate higher)
Alloimunization
Logistics/$/Error
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NeonatalTransfusionNeonatalTransfusion
Many premature newborns requiretransfusion
Iatrogenic: Frequent blood sampling,especially for monitoring blood gases mayresult in requirement to replace blood out.
Blood donor exposures in premature infants 9g Hgb @ 10-12 weeks
BW 1-1.5 kg, Nadir ~8 g Hgb.
BW
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Physiologic Factors:Physiologic Factors:
Neonatal anemiaNeonatal anemia
Loss of fetal hemoglobinDifferent Hbg-O2 dissociation curves: left
shifted 1/2 saturation is at 16 to 18mmHginstead of 24-26.
Fetal hemoglobin has reduced 2,3 DPGeffect
Decreased production of erythropoietin(Epo) in response to anemia
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Phlebotomy Blood LossesPhlebotomy Blood Losses
Mean levels of sampling = 0.8-3.1ml/kg/day.
Corresponds to 30%-300% of infantblood volume over course of stay inNICU
Transcutaneous O2 monitoring, smaller
volumes for ABG and lab studies helpreduce volume out.
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Treatment of Anemia ofPrematurityTreatment of Anemia ofPrematurity
Observation- Non-ill infants toleratesignificant anemia (see guideline)
TransfusionAllogeneic
Directed
Limited donor program
Autologous-harvesting autologous blood fromplacenta
Erythropoietin
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Guidelines forNeonatal RBCGuidelines forNeonatal RBC
TransfusionTransfusion
Definitions of severe, moderate, symptomaticmust be locally defined
No proven benefit of replacing iatrogenicblood loss by ml. Instead transfuse tomaintain minimum hct
Few studies guide transfusion triggers
Transfusion to treat apneic episodes iscontroversial
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Transfusion: Neonatal AnemiaTransfusion: Neonatal Anemia
How much: 10-20ml/kg
How fast: Over 2-4 hours
What: RBC product of choice:Controversial- See summary of StraussstudiesAge: # of days since unit donated
Anticoagulant
Irradiation
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Neonatal Rx: K+ & Age of UnitsNeonatal Rx: K+ & Age of Units
Extracellular Potassium (K+) rises withextended storage (CPDA-1: 78mmol/L in unit d 35,
45-50 @ d42 in AS); irradiation doubles rate No significant change in [K+] post small
volume (10-20ml/kg) given over 2-3 hours.
K+ problematic in massive transfusionCardiac Bypass, ECMO, Neonatal Exch Tx.
Give blood less than one week old, or washed
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Neonatal 2,3 DPGNeonatal 2,3 DPG
2,3 DPG levels are depleted during RBCstorage
Formerly used as an argument to providefresh blood to neonates
At least one study documents similar 2,3DPG levels in infants post-Tx of either fresh
or stored blood, proving that infants arecapable of 2,3 DPG regeneration
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Cold StorageCold Storage
RBC are stored at 2-6oC.
Rapid transfusion results in
hypothermia, hypoglycemiaRapid transfusion requires use of a
blood warmer-Use only FDA clearedwith alarm. Microwave ovens (not
intended for blood warming) have beenassociated with fatal hemolysis
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NeonatalTxNeonatalTx-- GlucoseGlucose
The anticoagulant preservative solutionin a 450ml bag of CPDA-1 red cells
contains 31grams of glucose.
This yields over 600 mg/dL glucoseconcentration.
Hyperglycemia is rarely of clinicalsignificance, but post transfusionhypoglycemia may ensue due tostimulation of insulin secretion
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NeonatalTxNeonatalTx-- HypocalcemiaHypocalcemia
The reason blood doesnt clot in the bagfollowing donation is complete chelation
of Ca++ by citrate. Excess citrate ispresent to ensure complete chelationregardless of donor calcium level.
Greatest risk of hypocalcemia: largevolume transfusion to neonates (bypass, ECMO, exchange), patients withacidemia or hepatic dysfunction.
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TT--Antigen ActivationAntigen Activation
Results in hemolysis of patient red cellsfollowing infusion of plasma component.
T-Antigen activation occurs followingNEC and sepsis, most typically fromgram negative organisms, such as
Clostridia.Mechanism: Enzymatic removal of sialic
acid residues from glycophorins,exposing a cryptantigen (T). All adult
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NeonatalTx.NeonatalTx.--DeGowinDeGowin
InventoryInventory
Infants < 1 Kg- Assigned to 1/2 unit-Aliquoted up to 42 days
Infants 1-1.3 Kg 1/4-1/2 unit
Infants >1.3 Kg use as needed
When unit is >14 days, no new
recipients assigned to that unitLarge volume transfusions (exchange,
cardiac bypass or ECMO) still requirelow [K+] source-fresh or washed.
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Erythropoietin vs.Transfusions forErythropoietin vs.Transfusions for
NeonatesNeonates
> 20 controlled trials of Epo Rx of neonates
No convincing evidence that Epo Rx substantially
reduces transfusion requirements in NICU patientsat greatest risk for the most transfusions, I.e. theprofoundly premature.
Currently 1.0kg requireRBC Tx
Nearly all infants
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Neonatal Autologous BloodNeonatal Autologous Blood
Placental cord blood collection:hematopoietic progenitors) & RBC for
Tx.Problems identified:
Patients for who it is easiest to collect are leastlikely to require transfusion
Difficult to predict who will subsequently requiretransfusion at or prior to delivery
High rate of bacterial contamination of placentalblood collections.
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NeonatalTransfusion: XNeonatalTransfusion: X
matchmatch
AABB Standard 5.15.5.1: ABO, Rh testeither neonate or mother for Ab
5.15.5.1.1Repeat ABO, Rh may beomitted rest of admission
5.15.5.1.2 If Ab Sc (-), no X-match is
required for intitial or subsequenttransfusions.
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NeonatalTransfusion:NeonatalTransfusion:
Xmatch IIXmatch II
If AbSc+, give RBC negative for that antigen,OR X-match compatible UNTIL Ab no longer
detectable (since antibodies are invariablymaternal, i.e. passive)
If non group-O neonate is to receive non-group O cells, test neonate for anti-A, and
anti-B, including by antiglobulin phase
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Intrauterine TransfusionIntrauterine Transfusion
By definition premature, Initial ABO, Rh typeunknown
Generally receive: Irradiated, CMV- (Ab orleukoreduced), group O cells, AB plasma.
Follow-up of HDN patients who received IUTrequired as they may have prolonged
erythroblastopenia, due to large unadsorbedload of maternal allo-RBC antibody
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Neonatal SummaryNeonatal Summary
Many premies Transf. Relatively large
amounts transfused
Passive Transfer of Ab
Lack ofIsohemagglutinnin
Long life expectancy
Immature immunesystem-Risk ofTAGVHD
Limited donor program
Citrate, K+, vol., Temp:special requirements
Test maternal serum
Lack back-type, no X-match required
Limit donors, boutiquecomponents
Irradiate for extremepremies, exchange Tx.
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Dilutional HemostaticDilutional Hemostatic
DysfunctionDysfunction
Occurs following massive RBC transfusion.
Neonatal levels of vitamin K dependant
factors normally lower. Thrombocytopenia may precipitate bleeding
Consider whole blood or plasma componentprime of large extracorporeal volume circuitslike Cardiac Bypass or ECMO.
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Neonatal Bleeding: PlateletsNeonatal Bleeding: Platelets
Normal range: Similar to adults
Clinical ramification of thrombocytopenia
(TCP) (
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NeonatalPlatelet RxNeonatalPlatelet Rx
Role for prophylactic platelet transfusionsunproven
Nonetheless, general consensus supportplatelet Tx for neonates with plt20K.
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NeonatalPlatelet Rx: HowNeonatalPlatelet Rx: How
much?much?
Goal = > 100K
Generally easily achieved by 5-10ml/kg of
platelet rich plasma from a unit of wholeblood. No additional concentration is requiredunless no concentrate with compatibleplasma is available (e.g. AB infant may
require plasma depletion of non-ABcomponent)Andrew JPed (1993) 123:285
Like RBC may require irradiation
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Guidelines forPlateletGuidelines forPlatelet
transfusion*transfusion*
Platelets < 100,000/ul and bleeding orclinically unstable (inc. IVH)
Platelets < 50,000/ul and invasiveprocedure
Platelets < 20,000/ul and no bleedingand clinically stable
* from Strauss, Chap 20 Neonatal Transfusion inAnderson, Ness Scientific Basis of TransfusionMedicine
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Pediatric plasma transfusionPediatric plasma transfusion
Most infants have low levels of vitamin K dependant factors,hence, all infants receive vitamin K at birth.
IM vitamin K is more effective than PO.
Many infants, especially premature normally have prolongedINR, hence prolongation ofINR, in absence of clinicalbleeding or significant risk of bleeding is NOT an indicationfor plasma transfusion. Rx is vit K.
Plasma 10-15cc/kg is usual dose Cryoprecipitate may be required if treating fibrinogen level