pediatric transfusion-risks and guidelines -cairo 9-01

8/8/2019 Pediatric Transfusion-Risks and Guidelines -Cairo 9-01

1/47

Pediatric

Transfusion

Risks and GuidelinesRisks and GuidelinesJed B. Gorlin, MD

Memorial Blood Center Minnesota


2/47

Trends in NeonatalTrends in Neonatal

TransfusionTransfusion

Transfusionpractices have

become moreconservative.

Survival continuesto improve despite

less bloodtransfused!

Extreme premies(


3/47

PediatricTransfusion:PediatricTransfusion:Risks and GuidelinesRisks and Guidelines

Review of overall risks of transfusionGuidelines for Pediatric Transfusion

Red Cell

PlateletPlasma


4/47

Risks ofTransfusionRisks ofTransfusion

Infectious Risks

Viral

Bacterial

Protozoa

Ricketsia

Other

?Prion

Non-infectious risks

Transfusion Reaction

Metabolic

Cardiac Overload

Dilutional Coagulopathy

TAGVHD

Alloimmunization


5/47

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


6/47

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


7/47

NonNon--Infectious RisksInfectious Risks

Transfusion Reactions

Metabolic complicationsDilutional coagulopathy

Cardiac Overload

TAGVHD

Alloimmunization-RBC, platelets


8/47

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


9/47

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


10/47

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


11/47


12/47

CMVatrisk guidelineCMVatrisk guideline

CMV Ab - pregnant women/fetus

Premature infants (


13/47

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


14/47

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.


15/47

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)


16/47

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 (


17/47

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


18/47

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


19/47

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


20/47

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


22/47

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


23/47

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.


24/47

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


25/47


26/47

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


27/47

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


28/47


29/47

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


30/47

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


31/47

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


32/47

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


33/47

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.


34/47

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


35/47

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.


36/47

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


37/47

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.


38/47

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.


39/47

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


40/47

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


41/47

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.


42/47

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.


43/47

Neonatal Bleeding: PlateletsNeonatal Bleeding: Platelets

Normal range: Similar to adults

Clinical ramification of thrombocytopenia

(TCP) (


44/47

NeonatalPlatelet RxNeonatalPlatelet Rx

Role for prophylactic platelet transfusionsunproven

Nonetheless, general consensus supportplatelet Tx for neonates with plt20K.


45/47

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


46/47

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


47/47

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

pediatric transfusion-risks and guidelines -cairo 9-01

Documents