17: BLOOD COMPONENT THERAPY

191

2. Patients at risk for TA-GVHD include recipients of donor-directed units

from first- and second-degree blood relatives, HLA-matched platelets, intra-
uterine transfusions, and massive fresh blood transfusions or exchange trans-
fusions, as well as patients with suspected or proven severe T-lymphocyte
immunodeficiency states (eg, DiGeorge syndrome).
3. For these high-risk patients, transfused blood components must be pro-
cessed to remove passenger WBC.
a. Leukoreduction (removal of passenger WBC)
i. Such so-called leukoreduction is almost always performed by filtra-
tion of the blood component through proprietary hollow-fiber filters
to which intact WBC adhere. (Centrifugation-based techniques are out-
dated.) Leukocyte counts can be reduced from 109 to 4–6 × 105 per RBC
unit (4 log unit reduction) with third-generation filters.
ii. Leukoreduction is effective in reducing HLA alloimmunization and
transmission of cell-associated viruses (especially herpes viruses [such
as CMV and HHV-8] and EBV)—as well as preventing some febrile
transfusion reactions.
b. Gamma-irradiation of cellular blood components delivers a dose of 25 Gy
and prevents subsequent WBC mitoses, and thereby TA-GVHD.
VI. Emergency transfusions.  For patients >4 months, uncross-matched (or “emer-
gency release”) blood is rarely transfused, because most blood banks can complete
an IAT cross-match within 1 hour. In cases of massive, exsanguinating hemor-
rhage, “type-specific” blood (ABO and Rh[D]-matched only), usually available in
10 minutes, can be used. If this delay is too long (as in severe fetomaternal hemor-
rhage), type O Rh(D)-negative RBCs should be used.
VII. Blood bank products
A. Red blood cells
1. Packed red blood cells (PRBCs)
a. Indications. PRBC transfusions are given to maintain the hematocrit (Hct)
at a level judged best for the clinical condition of the baby. The selected
target Hct is quite controversial and may vary greatly among neonatal units.
In general the goal is to maintain the Hct:
i. >35–40%  in the presence of severe cardiopulmonary disease.  The
severity of cardiopulmonary disease is assessed based on the level of
respiratory support (intermittent positive pressure ventilation [IPPV],
continuous positive airway pressure [CPAP], Fio2) required, symp-
toms of unexplained apnea and/or tachycardia, and/or poor growth.
ii. 30–35% for moderate cardiopulmonary disease or major surgery.
iii. 20–25% for infants with stable, so-called asymptomatic anemia.
b. Administration
i. Type.  PRBC transfused throughout infancy should be screened in
order to exclude donations from blood donors containing hemoglo-
bin S.
ii. Dosage. 10–20 mL/kg given over 1–3 hours (4 hours maximum). Use
the following formula as a guide:

Volume PRBC to transfuse (mL) = 1.6 × weight

(kg) × desired rise in Hct (%)

2. “Adsol” PRBCs. The traditional use of relatively fresh RBCs (<7 days stor-
age) has been largely replaced by the practice of transfusing aliquots of RBCs
from a dedicated unit of PRBCs stored for up to 42 days. This requires a sterile
connecting device and is done to diminish the number of donor exposures
among infants expected to require numerous transfusions during their stay
in the neonatal intensive care unit (NICU) (infants whose birthweight is
192 NEONATOLOGY

<1500 g). PRBCs are suspended in a citrate-anticoagulated storage solution

at an Hct of 55–60% stored at 1–6°C. The storage or additive solutions (AS or
Adsol-1, -3, or -5) contain various combinations of preservatives (dextrose,
sodium chloride, phosphate, adenine, and mannitol).
3. Citrate phosphate dextrose PRBCs. Because of concern about potential hepa-
torenal toxicity of adenine and mannitol, units of RBCs without extended
storage medium are used for large-volume transfusions such as exchange
transfusion and transfusions for major surgical procedures. PRBC units with
only small amounts of adenine and devoid of mannitol have a hematocrit
of 65–80% and a shelf life of 35 days. PRBC units with CPD formulations
(citrate-phosphate-dextrose) lacking both adenine and mannitol also have a
hematocrit of 65–80% but a shelf life of only 21 days. Washed Adsol PRBC
units are an alternative if these other PRBC units are unavailable.
4. Washed PRBCs. During storage, potassium is progressively released from
RBCs so that, by the end of the storage period, extracellular (plasma) potassium
levels approximate 50 and 80 mEq/L for Adsol and CPD units, respectively.
This leakage is increased in irradiated blood. For small-volume transfusions
the amount of infused K is, in general, of little clinical significance (0.3–0.4
mEq/kg per 15 mL/kg RBC transfusion). But it may become hazardous for
larger transfusion volumes such as in exchange transfusion. In such an event
and in the absence of fresh whole blood (<2–3 days old), RBCs (typically O
Rh[D] negative) washed free of their potentially hyperkalemic supernatant
using normal saline and then reconstituted to a hematocrit of 50–55% with
fresh frozen plasma (typically AB, termed “reconstituted whole blood”) can be
used. Irradiated reconstituted whole blood should be used for total exchange
transfusion.
B. Plasma—fresh-frozen plasma (FFP), thawed plasma. Donated whole blood is
centrifuged to separate the cells (RBCs) and the liquid (plasma). If the separa-
tion is done within 18 hours of the blood being donated and is frozen, it is called
fresh-frozen plasma. FFP contains albumin, immune globulins, and clotting fac-
tors (some retain much of their activity after thawing, eg, von Willebrand fac-
tor [vWF]) and factors V, VII, and VIII (their activity may be reduced during
processing before freezing).
1. Indications
a. Correction of coagulopathy due to inherited deficiencies of some clotting
factors, vitamin K deficiency (hemorrhagic disease of the newborn), or dis-
seminated intravascular coagulation (DIC). When available, clotting factor
concentrates are preferred to plasma in case of inherited clotting factor
deficiency. There are no single factor concentrates available for factors II,
V, and X. Prothrombin complex concentrates containing factors II, IX, and
X are used for factor II and X deficiencies.
b. Prophylaxis for dilutional coagulopathy that may ensue during massive
blood transfusion administered for replacement of blood loss in excess of
half of the blood volume.
c. Preparation of reconstituted whole blood from washed PRBCs for total
exchange transfusion.
d. Although FFP provides excellent colloid volume support, it is not recom-
mended for volume expansion or antibody replacement because safer com-
ponents are available for these purposes.
2. Administration
a. Transfused plasma should be ABO compatible with the patient’s blood
group. Incompatible antibodies in the donor plasma (such as anti-A or -B
antibodies in group O plasma) may rarely, if given in sufficient volume,
result in an acute hemolytic reaction in the transfused patient.
b. Dosage: 10–20 mL/kg over 1–2 hours (4 hours maximum).
17: BLOOD COMPONENT THERAPY 193

c. Rapid transfusion may result in transient hypocalcemia due to the sodium

citrate that is added to the original donated blood. If rapid infusion of FFP
is needed, a small bolus of calcium chloride (3–5 mg/kg) may be considered.
C. Cryoprecipitate. Prepared from FFP by thawing it at 1–6°C. In this temperature
range, a cryoprecipitate forms and is separated from so-called cryo-poor super-
natant plasma by centrifugation. The pellet is then frozen as cryoprecipitate. Prior
to use, it must again be thawed and dissolved off the interior surface of its plastic
bag with normal saline (with a total volume of 10–15 mL). Cryoprecipitate is a
concentrated source of the following blood clotting proteins: factor VIII, vWF,
fibrinogen, and factor XIII (with some other proteins, eg, fibronectin).
1. Indications
a. To restore fibrinogen levels in patients with acquired hypofibrinogenemia
(as occurs in DIC and massive transfusion)
b. Factor XIII in deficient patients
2. Administration
a. Like plasma, it should be ABO compatible with the recipient’s blood group.
b. Dosage: 10 mL/kg (0.1–0.2 U/kg raises fibrinogen by 60–100 mg/dL).
c. Infusion should be completed within 6 hours of thawing.
D. Platelets.  Prepared from whole blood donations by centrifugation (termed
“random donor”) or by automated apheresis (termed “single donor” or “platelets
pheresis”). Each random donor unit contains 5.5 × 1010 platelets in 50–70 mL
of anticoagulated plasma. Each single-donor unit contains 3 × 1011 platelets,
typically in 200–300 mL of anticoagulated plasma. Both are stored at room tem-
perature (20–24°C) with agitation for a maximum of 5 days.
1. Indications. There are no absolute guidelines regarding platelet counts that
necessitate transfusion.
a. In general, platelet transfusion is indicated for platelet counts below 50,000/
μL.
b. In the presence of active bleeding or prior to surgery, this “transfusion
trigger” may be raised to 100,000, while in a nonbleeding, stable neonate
platelet counts as low as 20,000–30,000 may be tolerated.
c. In septic patients, platelet increments after transfusion may only be tran-
sient.
d. Because of room temperature storage, bacterial contamination of platelet
units is actively sought, typically by culture or direct testing of each com-
ponent.
e. Increased mortality and morbidity have been described among preterm
infants receiving multiple platelet transfusions.
2. Administration
a. Infant and donor should be ABO identical if possible. When ABO-identical
platelets are unavailable, group AB platelets are the most suitable substitute.
However, the frequent unavailability of group AB platelets causes the use of
group A platelets for group B recipients and vice versa. Group O platelets are
the least suitable for non–group-O infants, as passively transfused anti-A
or -B antibodies may lead to hemolysis.
b. Rh(D)-negative platelets should be given whenever possible to Rh(D)-
negative patients—especially female infants.
c. For infants with alloimmune thrombocytopenia (AIT), platelets lacking
platelet-specific antigens (HPAs) to which antibodies are directed are
required. If such platelets are unavailable, then HPA 1a, 5b–negative plate-
lets may be given since these will be compatible in 95% of AIT cases among
Caucasians. If anti-HPA antibodies are not demonstrated, then anti-HLA
antibodies may be present requiring HLA-matched platelets.
d. Dosage: 10–20 mL/kg IV should raise neonatal platelet counts by 60,000–
100,000/μL.