Unit 11 Neonatal and
Obstetrical Transfusion
Practice
Terry Kotrla, MS, MT(ASCP)BB
Introduction


Neonatal period – birth to 4 months.
Indications for transfusion DIFFERENT




Weight
Gestational age
Circumstances of delivery
Maturation
Introduction

Ill infants most transfused patients in hospital.



Iatrogenic blood loss carefully monitored.
Once significant, transfuse
Transfusion service must provide specialized
service



Minimize donor exposure if possible.
Use one unit with satellite bags
Use sterile docking device
Sterile Docking



Original bag on left, aliquot bag on right.
Tubing inserted in device and welds the two
together, maintains CLOSED system.
Blood squeezed over.
Fetal and Neonatal Erythropoiesis


Appropriate transfusion practice requires knowledge of
neonatal physiology and careful clinical observation.
As embryo develops predominant sites of hematopoiesis
change:





at about the 9th week of gestation shifts from wall of yolk sac to liver.
at about the 24th week from liver to bone marrow.
Hematopoiesis regulated by gradually increasing
erythropoietin levels stimulated by low oxygen tensions
during intrauterine life.
At 40 weeks (full term), normal infants have cord blood
hemoglobin of 19 +/- 2.2 g/dL.
Neonates of lower birth weight have lower normal
hemoglobin levels.
Fetal and Neonatal Erythropoiesis

Fetal red cells have life span of 45-70 days, 53-95%
hemoglobin F




Hemoglobin A replaces hemoglobin F after birth



Physiologically adapted to low intrauterine oxygen tensions
High oxygen affinity allow red cells to acquire oxygen from
maternal RBC throughout pregnancy and release tissues.
High oxygen affinity results in poor tissue oxygenation after birth.
Oxygen delivery to tissues remains satisfactory despite a
physiologic fall in hemoglobin concentration.
Oxygen dissociation curve shifts to the right, reflecting improving
oxygen delivery to the tissues.
Premature infants have lower hematocrits and greater
percentage of hemoglobin F in their RBC than term newborns.
Fetal and Neonatal Erythropoiesis



As tissue oxygenation improves, erythropoietin
decline and erythropoiesis diminishes.
Decline in RBC produces a "physiologic anemia of
infancy“.
Normally developing infant maintains adequate
tissue oxygenation despite lower hemoglobin levels.
Unique Aspects of Neonatal Physiology



Differences between newborns and adults
dictate differences in transfusion practice.
Newborns are small and physiologically
immature.
Those requiring transfusion are often
premature, sick and unable to tolerate
minimal stresses.
Unique Aspects of Neonatal Physiology

Infant size





Full-term newborns blood volume approximately 85 ml/kg
Premature infants average blood volume of 100 ml/kg.
Survival rates continue to improve for infants weighing 1000
g (2.2 lbs) or less at birth
Transfusion service must provide blood components for
patients whose total blood volume is less than 100 mLs.
Small blood volumes and need for frequent laboratory test
makes replacement of iatrogenic blood loss most common
indication for transfusion.
Unique Aspects of Neonatal Physiology


Infants do not compensate for hypovolemia well.
Results in diminished cardiac output, resulting in





poor tissue perfusion,
low tissue oxygenation and
metabolic acidosis.
Bone marrow responds more slowly to anemia.
If hemolysis occurring due to maternal antibody may
be no increased erythropoiesis for 2-3 weeks.
Unique Aspects of Neonatal Physiology

Cold stress (hypothermia) causes exaggerated
effects:





increased metabolic rate
hypoglycemia
metabolic acidosis
tendency to apneic episodes that may lead to hypoxia,
hypotension and cardiac arrest.
Blood for transfusion should be warmed if given in
large amounts, small amounts reach RT in about 20
minutes and does not need to be warmed.
Unique Aspects of Neonatal Physiology




Immunologically immature, antibodies present in plasma
originate almost entirely from maternal circulation.
IgG only immunoglobulin class that crosses the placenta.
Passively acquired antibody conserved during the neonatal
period due to slow catabolism by the fetus.
Infants exposed to an infectious process in utero or shortly
after birth may produce small amounts of IgM detectable by
sensitive techniques, but rarely form RBC antibodies of either
class during the neonatal period.
Transfusion Associated Graft versus Host
Disease (TA-GVHD)



TA-GVHD reported in newborns receiving
intrauterine transfusion followed by postnatal
exchange transfusion.
Lymphocytes given during intrauterine transfusion
may have induced host tolerance, so that
lymphocytes given in subsequent exchange
transfusion were not rejected in the normal way.
GVHD not felt to be significant clinical problem for
immunologically normal newborns who receive
multiple exchange transfusions.
Transfusion Associated Graft versus Host Disease
(TA-GVHD)




Irradiation of blood kills immunologically
competent lymphocytes.
Irradiated blood given to low birth weight, low
gestational age or septic premature neonates such
infants are immunologically more vulnerable to TAGVHD.
Blood for intrauterine transfusion should be
irradiated.
Any directed donor blood from a relative should be
irradiated.
Unique Aspects of Neonatal Physiology –
Metabolic Problems



Immature kidneys have reduced glomerular filtration
rate and concentrating ability, the newborn may have
difficulty excreting potassium, acid and/or calcium
loads.
Acidosis or hypocalcemia may also occur
postransfusion because immature liver metabolizes
citrate in banked blood inefficiently.
Studies have shown older units do not affect the
infant for routine transfusion purposes.
Cause of Hemolytic Disease



Maternal IgG antibodies directed against an antigen
of paternal origin present on the fetal red blood cells.
IgG antibodies cross the placenta to coat fetal
antigens, cause decreased red blood cell survival
which can result in anemia.
Produced in response to previous pregnancy with
antigen positive fetus OR exposure to red blood
cells, ie transfusion.
Unique Aspects of Neonatal Physiology – 2,3DPG





Tissue oxygenation poor due to high percentage of hemoglobin F.
Hemoglobin F does not release oxygen to the tissues like adult hemoglobin.
Respiratory distress syndrome (RDS) or septic shock have decreased levels of 2,3DPG, alkalosis and hypothermia can further increase the oxygen affinity of
hemoglobin.
2,3-DPG levels decrease in stored blood, newborns should be given freshest blood
available, less than 5 days old if possible.
Controversy in the field about the practice of using fresh blood.



Greater importance to decrease donor exposures rather than give fresh blood.
Allow CPD donor units to be put on hold for infant for 21 days.
Exception is for massive transfusion
Cytomegalovirus (CMV) Infection




Infection by CMV may occur in the perinatal period, either
in-utero or during birth, by breast feeding or by close contact
with mothers or nursery personnel.
CMV mays also be transmitted by transfusion, virus seems to
be associated with leukocytes in blood and components.
Infection in newborns is extremely variable in its
manifestations, ranging from asymptomatic seroconversion to
death.
Symptomatic infection may produce pulmonary, hepatic,
renal, hematologic and/or neurologic dysfunction.
Cytomegalovirus (CMV) Infection


This neonate was found to have respiratory distress, an
extensive rash and hepatomegaly.
Results of CMV IgM and IgG tests and both serum and
plasma DNA polymerase-chain-reaction assays were positive.
Cytomegalovirus (CMV) Infection


Epidemiology and prevention of post transfusion CMV in neonatal
patients have been under intense investigation.
The following observations have been noted:





Where CMV rate is high, symptomatic infection is low.
Babies of seropositive moms unlikely to develop CMV.
Premature infants born of seronegative mothers, weigh less than 1200 grams
and require multiple transfusions at risk for symptomatic postransfusion
infections.
The risk of CMV increases with number of donor exposures.
Risk of transmission decreases by using seronegative donors or components
depleted of leukocytes.
Cytomegalovirus (CMV) Infection

Standards states that in geographic areas where
postransfusion CMV transmission is a problem,
blood with minimal risk of transmitting CMV be used
for:




newborns weighing less than 1200 g,
born to mothers who lack CMV antibodies or
whose antibody status is unknown.
Most blood banks make it standard practice to
transfuse all infants with CMV negative blood.
Hemolytic Disease of the Fetus and
Newborn - HDFN



HDFN, red cells of fetus coated with IgG
alloantibody of maternal origin, directed against
antigen of paternal origin present on fetal cells.
IgG coated cells undergo accelerated destruction,
both before and after birth.
Clinical severity of the disease is extremely
variable, ranging from intrauterine death to a
condition that can be detected only by serologic tests
on blood from an apparently healthy baby.
HDFN - Pathophysiology



Shortened RBC survival causes fetal hematopoietic
tissue increase production of RBCs, causes increase
in nucleated red cells (NRBCs).
Organs containing hematopoietic tissue increase in
size, particularly liver and spleen
(hepatosplenomegaly).
If increased hematopoiesis cannot compensate for
the immune destruction, anemia becomes
progressively more severe.
HDFN - Pathophysiology



Severely affected fetus may develop high output
cardiac failure with generalized edema, a condition
called hydrops fetalis, death may occur in utero.
If live-born, severely affected infants exhibit heart
failure and profound anemia.
Less severely affected infants continue to experience
accelerated red cell destruction, which generates
large quantities of bilirubin.
HDFN - Pathophysiology




In-utero fetal bilirubin processed by maternal
liver.
After birth neonatal immature liver takes over.
Deficient in uridine diphosphoglucoronyl
transferase, bilirubin rises.
Bilirubin 20mg/dL> results in mental
retardation or death, condition known as
kernicterus.
Kernicterus


Kernicterus (bilirubin encephalopathy)
results from high levels of indirect bilirubin
(>20 mg/dL in a term infant with HDN).
Kernicterus occurs at lower levels of bilirubin
in the presence of acidosis, prematurity,
hypoalbuminemia and certain drugs (e.g.,
sulfonamides).
Kernicturus





Affected structures have bright yellow color.
Unbound unconjugated bilirubin crosses blood-brain barrier and, because it is
lipid soluble, penetrates neuronal and glial membranes.
Bilirubin is thought to be toxic to nerve cells
Mechanism of neurotoxicity and reason for topography of lesions are not known.
Patients surviving kernicterus have severe permanent neurologic symptoms
(choreoathetosis, spasticity, muscular rigidity, ataxia, deafness, mental
retardation).
Three Classifications of HDN



ABO
“Other” – unexpected immune antibodies
other than anti-D – Jk, K, Fy, S, etc.
Rh


Immune anti-D alone
Immune anti-D along with other Rh antibodies –
anti-C, -c, -E or –e.
Maternal Immunization




Fetal cells possessing paternal antigen mother
does not possess enter her circulation and
stimulate antibody production.
D antigen most immunogenic but other blood
group antigens may also immunize.
Fetal cells enter maternal circulation during
pregnancy.
Biggest exposure during birth.
Maternal Immunization


Can occur with exposure to <0.1mL
Immunization to D correlates with  volume
of RBCs entering D neg mom’s circulation.
Maternal Immunizing Events

Other than birth can be due to:







Amniocentesis
Miscarriage
Abortion
Chorionic villus sampling
Cordocentesis
Blunt trauma to the abdomen
Rupture of an ectopic pregnancy
Maternal Immunization - Transfusion




Severe HDFN in D neg women transfused
with D pos RBCs and develop anti-D
Must give D neg RBC and platelet products to
females.
If D pos platelets or granulocytes given must
give Rh prophylaxis, i.e., RhIg
Avoid directed donation from husband to wife
ABO Hemolytic Disease





Mother group O, baby A or B
Group O individuals have anti-A, -B and –A,B in
their plasma, fetal RBCs attacked by 2 antibodies
Can occur in any ABO incompatible pregnancy
Occurs in only 3%, is severe in only 1%, and
<1:1,000 require exchange transfusion.
The disease is more common and more severe in
African-American infants.
HDFN Other Than ABO

If this pregnancy is the immunizing event first
baby is not affected or only mildly affected.




Primary immune response – IgM
During pregnancy IgG may not be produced in
sufficient quantity to cause problems.
Severity of HDFN in future pregnancies due
to “other” immune antibodies variable.
If anti-D future pregnancies severely affected.
Prenatal Serologic Tests


ABO/D type and antibody screen.
If antibody screen positive




Identify antibody
Determine clinical significance
If clinically significant patient history
important, previously affected infant.
IgM antibodies are not of concern
Prenatal Serologic Tests




In primary immune response IgM antibodies
may demonstrate high thermal amplitude.
Treat serum with 2ME or DTT to determine if
IgG is present.
Antibody may be present but fetus may be
antigen negative.
If anti-D test father to determine zygosity of
D antigen.
Amniotic Fluid Analysis






Assess probable severity of HDFN.
Based on history of antibody AND maternal
history with previous pregnancies.
Monitor antibody titer, perform if rising.
Measure bile pigments at 450 nm
Level correlates with severity of hemolysis.
Result will determine action plan.
Amniotic Fluid Analysis


Maternal titer greater than 32 for anti-D and 8 for anti-K OR four fold increase in
titer indicates need for analysis of amniotic fluid.
Amniocentesis






Perform at 28 wks if HDN in previous child
Perform at 22 wks if previous child severely affected
Perform if maternal antibody increases before 34th wk.
High values of bilirubin in amniotic fluid analyses by the Liley method or a
hemoglobin concentration of cord blood below 10.0 g/mL.
Type fetus -recent development in fetal RhD typing involves the isolation of free
fetal DNA in maternal serum. In the United Kingdom, this technique has virtually
replaced amniocentesis for fetal RhD determination in the case of a heterozygous
paternal phenotype
Maternal plasma exchange may be instituted if the fetus is too young for
intrauterine transfusion.
Amniocentesis
Amniotic Fluid Analysis



Zone 1- unaffected or mildly affected
Zone 2 – Deliver at 36-38 weeks based on fetal lung maturity.
Zone 3 – Seriously affected, intrauterine transfusion and
preterm delivery indicated.
Amniotic Fluid Analysis
Amniotic Fluid Analysis


Weigh risks in severely affected pregnancy
Respiratory Distress Syndrome (RDS)



Due to inadequate surfactant and lecithin
Determine fetal lung by L/S ratio and
phosphotidylcglycerol (PG) in amniotic fluid.
If lungs not mature, intrauterine transfusion.
Amniotic Fluid Analysis and Fetal
Blood Sampling

Amnio can cause fetomaternal hemorrhage
(FMH)




If amnio done for other reasons and woman
unsensitized D neg, give RhIg
D type of fetus is unknown, prevent
immunization
Cordocentesis – draw blood from umbilical
cord for laboratory analysis
Use non-invasive procedures when possible.
Intrauterine Transfusion (IUT)




Performed after careful evaluation due to high
risk to fetus.
Given to prevent hydrops fetalis and fetal
death.
Rarely feasible before 20th week gestation.
Once started administer every 2 weeks.
Intrauterine Transfusion (IUT)

Blood must be:







Less than 5 days old
Low risk of CMV (CMV neg or safe)
Hematocrit 80% or higher
O negative and COMPATIBLE WITH MOM
Lack antigens which antibody(ies) are directed.
Irradiated
75-175mLs determined by fetal size and age
Intrauterine Transfusion (IUT)

After multiple IUTs RBC testing will not be
accurate:




Will type as O neg as 90% of circulating RBCs
will be donor cells.
Direct Antiglobulin test will be negative
Indirect Antiglobulin Test will be positive.
Cord bilirubin not an accurate indicator of rate
of hemolysis or of likelihood of need for
exchange transfusion after birth.
Intrauterine Transfusion (IUT)






Done in the hospital
Ultrasound to determine the position of the fetus and
placenta.
Local anesthetic to numb site.
Medicate fetus to stop or slow movement.
Ultrasound used to guide needle through abdomen
into fetus's abdomen or umbilical cord vein.
Peritoneal cavity versus cord vein.
Intrauterine Transfusion (IUT)
Intrauterine Exchange Transfusion





Replace fetal blood with donor blood.
Use ultrasound to cannulate umbilical vein.
Take blood sample H&H and verification of
catheter location in the fetal circulation.
Small volume donor blood transfused, wait,
small volume removed.
EXCHANGE fetal blood with donor blood.
Intrauterine Transfusion - Risks




Fetal Loss - risk variable depending on
condition of fetus, overall 1-2%, range
<1% - 50%.
Bradycardia - common but usually
transient
Bleeding - usually transient and mild
Preterm Labor
End of Unit 11 Part 1