PROTOCOL FOR BLOOD COMPONENT THERAPY

PLATELET TRANFUSIONS

PLATELET TRANFUSIONS IN NICU

The incidence of thrombocytopenia among all neonates admitted in NICU is between 18 % - 35%1.
The incidence increases to approximately 70% in ELBW infants2 . In a study conducted in a NICU
in USA , it was found that approximately 9%3 of the admitted newborns received platelet
transfusions

INDICATIONS FOR PLATELET TRANSFUSIONS

Thrombocytopenia is a risk factor for bleeding in neonates. But there is a poor correlation between
severity of thrombocytopenia and clinically significant bleeding. There is no debate that in a
bleeding infant with thrombocytopenia, platelet tranfusion will benefit in reducing the extend of
bleeding. But however the literature is scarce when it comes to prophylactic platelet transfusion in
preterm infants.
Platelet transfusions are associated with its own significant risk factors and they should be weighed
against the benefits.

Recommended transfusion levels for neonates4

Platelet count ( x 109) Guideline

<20 Transfuse all

20-49 Transfuse if -
1. BW <1000 and < 8 days old
2. Prior to surgery
3. Post- operative period (72 hours)
4. Concurrent coagulopathy
5. Previuos significant IVH grade 3 or 4

50-100 1. Active bleeding

2. Before or after neurosurgical procedures

PLATELET TRANSFUSIONS - PREPARATION, STORAGE , SPECIFICATIONS AND

ADMINISTRATION5

PREPARATION

Whole blood derived platelets via buffy coat method is the platelet preparation that is preferred in
neonates. There is no clear advantage of apheresis derived single donor platelets over whole blood
derived random donor platelets in neonates.

STORAGE

A closed system is preferred for preparation and platelets can be stored at 22°C ± 2°C with
continual gentle agitation for up to 5 days.
SPECIFICATIONS

ABO group - Administration of ABO non-identical platelets is acceptable only when platelet
concentrates are in short supply.Group O platelets should only be used for group A, B and AB
patients if they have been tested and labelled as negative for high-titre anti-A and anti-B
RhD group stated as positive or negative - If Rh positive platelet is infused into Rh negative
newborn, anti-D prophylaxis is to be given (250 IU i.v.) and further transfusions should be of Rh
negative only
Components should be negative for cytomegalovirus (leuco-depleted and from CMV seronegative
donors) and should contain > 40 x 109 ⁄ unit of platelet concentrate.

ADMINISTRATION

1. All platelets should be visually inspected for leakage, unusual smell, turbidity, expiry date,
other details such ABO/ Rh grouping
2. Platelets should be transfused immediately after dispatch from the blood bank
3. Dosing - 10-20 ml/kg should be administered over 30 minutes
4. Post tranfusion platelet count should be done at 1 hour or at 24 hours post transfusion
depending on the clinical scenario

FRESH FROZEN PLASMA (FFP) TRANFUSION

FFP is defined as a blood component prepared from whole blood or collected by apheresis, frozen
within a specified time limit and at a temperature such as to preserve the labile clotting factors
adequately

FFP USAGE IN NICU

In studies by Baer6 and Puetz7 the prevalence of FFP transfusion in neonates was 6% and 12%
respectively. Both studies reported a significant proportion of use outside of published
recommendations
In a recent prospective study by Motta et al8, it was found that 8% of admitted neonates received
FFP transfusion and a high proportion (60%) of transfusions were not compliant with guidelines
and 63% of transfused neonates received FFP prophylactically, without any evidence of bleeding.

INDICATIONS9,10,11

1. Haemorrhagic disease of the newborn (HDN) -When haemorrhage due to HDN occurs, FFP
(10–20 ml/kg) is indicated, as well as intravenous vitamin K 0.5 mg i.v. (<1 kg); 1 mg i.v.(>1
kg) ( LOE-C, SOR-1)
2. Neonates with coagulopathy (defined as PT or APTT - more than 1.5 times the normal) and
bleeding - Should receive approximately 15 ml/kg of FFP as well as a dose of intravenous
vitamin K ( LOE-C, SOR-1)
3. Neonates with coagulopathy (defined as PT or APTT -more than 1.5 times the normal ) and at
risk of bleeding from an invasive procedure - Should receive approximately 15 ml/kg of FFP
as well as a dose of intravenous vitamin K ( LOE-C, SOR-2)
4. Single factor deficiencies -Fresh-frozen plasma should only be used to replace single inherited
clotting factor deficiencies for which no virus-safe fractionated product is available which
applies only to Factor V. ( LOE-C, SOR-1)
5. DVET - FFP can be used along with PRBC for reconstitution if fresh whole blood is not
available ( LOE-C, SOR-1)
6. Surgery - In all infants with abnormal coagulation profile and about to undergo surgery ( LOE-
C, SOR-2)

There is no role for FFP transfusions in -

1. Abnormal coagulation profile in any setting (Eg RDS B1/ Sepsis C1/ Liver failure/ Therapeutic
hypothermia C2) with no bleeding
2. Prophylaxis for bleeding in sepsis / liver failure (C1)
3. Volume expansion (B1)
4. Hypotension (B1)
5. Source of albumin / nutrition
6. Partial exchange transfusion (B1)
7. Prevention of IVH in preterm infants (A1)
A - High quality evidence, B- Moderate quality evidence, C- Low quality evidence
1-Strong strength of recommendation, 2- Weak strength of recommendation

ROLE OF PT/ INR / APTT

1. No role for performing PT/aPTT in all cases of sepsis unless DIC is suspected with ongoing
bleeding
2. Clinical setting of Sepsis with suspected DIC with minor bleeding - PT/aPTT to be done
3. Post FFP transfusion coagulation tests - Role for repeat PT/aPTT post FFP transfusion very
limited. May be useful if FFP was transfused to correct coagulation abnormality prior to surgery
or invasive procedure. If FFP is given because the patient is bleeding, the clinical response may
well be the best indicator of effectiveness of transfusion
4. Repeat FFP transfusion -The factors that are predominantly affected in DIC are fibrinogen (t1/2
- 2-4 days), factor XIII ( t1/2 - 5-7 days), Factor V (t1/2- 2-4 hours) and factor VIII (t1/2 -
hours).Shortest t1/2 is for factor V (2-4 hours). If bleeding persists even after FFP transfusion,
it might be because two reasons -
A. Factors are not raised to a considerable level - In this context, the bleeding will never stop post
FFP.
B. Factors are depleted due to consumptive coagulopathy or due to natural clearing - Here the
bleeding will stop post FFP and may ensue after some time
Repeat FFP can be considered in such scenarios after taking into account the chances of circulatory
overload.
FFP TRANSFUSIONS - PREPARATION, STORAGE , SPECIFICATIONS AND
ADMINISTRATION5

PREPARATION

FFP is prepared from whole blood either by centrifugation or by apheresis; there is no qualitative
difference between these two. It is frozen for storage at -30 degree celsius, the time between
collection and storage is no longer defined provided the specifications are met. Can be stored upto
24 months at -30 degree celsius. When frozen, the packs may become vulnerable for leaks and
should be handled with care. Thawing should be done at 37 degree celsius. Thawing could be done
by water baths, dry ovens ( preferred), microwave ovens. Water bath can increase the risk of
bacterial contamination, thawing time is 20 minutes for 2 packs.
SPECIFICATIONS

ADMINISTRATION

1. Thawed plasma should be kept at 4 degree celsius if there is a delay in transfusion. It can be
stored at 4 degree celsius for 4 hours ( if factor VIII replacement is the primary goal) or 24
hours ( if factor VIII replacement is not the primary requirement).
2. Dosing -10- 20 ml/kg over 2 hours; Higher end of dosing to be considered for major bleeding.
RED BLOOD CELL TRANSFUSION

INCIDENCE OF PRBC TRANFUSION IN NICU12,13

Preterm critically ill newborns are among the most heavily transfused patient groups. Various
studies show that about 80 to 90 % of VLBW babies admitted in NICU receive PRBC transfusions
for anemia

INDICATIONS FOR PRBC TRANFUSIONS IN PRETERM INFANTS14

Post natal age Respiratory support* No respiratory support

Week 1 11.5 g/dL (35%) 10 g/dL (30%)
Week 2 10.0 g/dL (30%) 8.5g/dL (25%)
Week 3 and older 8.5 g/dL (25%) 7.5g/dL (23%)
*Respiratory support is defined as FiO2 >25% or need for mechanical increase in airway
pressure

INDICATIONS FOR PRBC TRANSFUSIONS IN TERM INFANTS15

Hb<13g/dL Severe pulmonary disease or severe cardiac disease

Hb < 10 g/dL Moderate pulmonary disease
Hb < 10 g/dL Prior to surgery
Hb <8 g/dL Symptomatic anemia

PREPARATION16

1. Red blood cell preparations contain anticoagulant/ preservative solutions [CPD - citrate
(anticoagulant), phosphate (buffer), dextrose( source of metabolic energy)]- Shelf life of 21
days. Addition of mannitol and adenine (CPDA-1) to this solution increases the shelf life to 35
days (Hct - 70%).
2. Extended storage media increases the shelf life to a further 42 days (Hct - 60%) & also reduces
donor exposure. Though ES media are safe and efficacious compared to CPDA-1 for small
volume transfusions; for large volume transfusions, data regarding safety is lacking.
3. For large volume transfusions (>25 ml/kg) or for rapid infusions, fresh RBC solutions (<7 days)
should be used
SPECIFICATIONS14

1. Newborns ABO group is assigned on the basis of the A/B antigen present on the RBCs (forward
typing) since anti-A and anti-B are not present in the serum at birth
2. Maternal blood is used as a source of serum for cross matching for antibodies since maternal
antibodies are passively transferred
3. When maternal antibodies are detected, the blood should be ABO and Rh specific but negative
for the identified antibody
4. Uncross-matched group O Rh negative blood can be used in perinatal emergencies

ADMINISTRATION14

1. Volume of blood(ml) = BV X Body weight X (Expected Hct - Observed Hct) / Hct of the blood
transfused
2. The maximum calculated volume should not exceed 20 ml/kg at a time
3. Rate should not exceed 7 ml/kg/hr ; 2 ml/kg/hr in the presence of congestive heart failure
4. No need for routine administration of furosemide except when there is presence of congestive
heart failure (dose 1mg/kg i.v.; mid-transfusion)
5. Warming small-volume RBC aliquots before transfusion is not necessary. However,
hypothermia can develop after massive transfusion unless the RBCs are first warmed. Warming
can be done in water baths or in warm-air incubators for 30 minutes before transfusion
6. Overheating, with resultant hemolysis, may occur when syringe aliquots are placed under
radiant warmers or phototherapy lights
7. When phototherapy is in progress, the blood component and tubing should be shielded to
prevent overheating and hemolysis.
8. At the other extreme, freezing and lysis may occur if RBC products are stored in unmonitored
refrigerators or freezers.

SPECIAL RBC PREPARATIONS17,18

1. Leukoreduction - All RBC preparations for neonates should be leukoreduced ( Leucocyte count
- 5 X 106 per bag) Results in a substantial reduction in CMV infection (by 92% to 93%)
2. Gamma irradiation -In all preterm babies <1200 gms, intrauterine transfusions, double volume
exchange transfusions , suspected immunodeficiency- Reduces the risk of Graft Vs Host
reaction
3. Washed RBCs -If fresh blood is not available (< 7 days) in cases of large volume transfusion
(>20 ml/kg) / DVET (<3 days) - To reduce the risk of hyperkalemia

DVET19

1. A double-volume exchange transfusion results in removal of approximately 85% of the

neonate’s RBCs but only 25%–45% of bilirubin and/or maternal alloantibody.
2. Either stored WB if available or reconstituted WB can be used for neonatal exchange
transfusions. Blood chosen for the exchange should be fresh [ preferably < 3 days, CPD(A)
units].
3. If only older CPDA units or extended storage units are available, the RBC units should be
washed.
4. All components should be CMV risk-reduced, gamma-irradiated, and sickle-negative, with final
hematocrit of 40%–50%
5. Rh isoimmuniation - Type-O Rh-negative blood cross-matched against the mother to be used.
6. In ABO incompatibility - the blood must be type-O and Rh-negative or Rh-compatible with the
mother and infant.
7. The traditional push–pull method with a single vascular access, usually the umbilical vein
8. Aliquots with a maximum of 5 mL/kg at a rate not exceeding 5 mL/kg every 3 minutes to avoid
rapid fluctuations in intracranial pressure
9. The duration of the exchange is usually 1 to 2 hours.

PARTIAL EXCHANGE TRANSFUSION

1. Partial exchange transfusion is done for mainly two purposes - Polycythemia and immune
hydrops with anemia ( Hb <10 g/dL)
2. Partial exchange in immune hydrous with anemia should be done immediately after birth and if
feasible in the labour room
3. PRBC - O negative should be used, cross matching with maternal serum should be done prior to
delivery and blood should be ready at the time of delivery

4. In hydrops with severe anaemia -

- PRBC (ml) = Blood volume x weight x Expected Hct- Observed Hct
Hct of blood- Observed Hct

- Expected Hct could be taken as 30-40 % depending on degree of respiratory support required
- In cases of severe anaemia ( Hb<7 g/dL), simultaneous withdrawal of baby’s blood by one
person and pushing of the PRBC by another person to be done in aliquots of 5 ml/kg.

5. In cases of polycythemia -
- PRBC (ml) = Blood volume x weight x Observed Hct- Expected Hct
Observed Hct
- Equal volume of normal saline is given via an infusion pump through a peripheral vein while
blood is simultaneously withdrawn from the baby, to be completed over a period of 30 minutes
using aliquots of 5 ml/kg.
RISKS OF TRANSFUSION THERAPY18

METABOLIC RISKS

Hypoglycemia 1. DVET - Incidence - 1.4%-3.6%; Due to intra procedural

hyperglycemia
2. Small volume transfusions - Maintenance fluids should not be
suspended during blood transfusions. If maintenance fluids are
suspended, the GIR reduces to 0.2-0.5 mg/kg/min and hypoglycemia
ensues.

Hyperkalemia 1. When old blood (>7 days) is used for large volume transfusions (25
ml/kg)
2. Rapid infusion (old and new) ( 10-20 ml/kg over 10-20 min), when
RBCs were irradiated >24 hours prior
3. Washing of RBCs in the above mentioned senarios decreases the
risk.
4. Maximum rate should not exceed 0.5 ml/kg/min in emergency
situations

Hypocalcemia 1. More likely in large volume transfusions such as DVET due to

citrate toxicity
2. Incidence - Healthy infants undergoing DVET - 35%
(asymptomatic) & 5%(Symptomatic); Sick infants undergoing
DVET - 40%(asymptomatic) and 8% (Symptomatic
3. QT interval monitoring during the procedure , prevention by
reducing potentiating factors such as alkalosis, hypomagnesemia,
hypothermia, hyperkalemia
IMMUNOLOGICAL RISKS

Hemolytic 1. Rare in neonates; most common is due to ABO

transfusion reactions incompatibility
2. Transfusion to be stopped, Clerical check to be done
3. Patients – Hb, DCT, Bilirubin, LDH to be sent
4. Blood bank informed, Blood sent for Culture
Febrile non- 1. Due to pyrogens from leukocytes
hemolytic reactions 2. Incidence reduced to 0.1-3% after the introduction of leukoreduction
3. Transfusion stopped and more serious reaction ruled out

Allergic transfusion 1. Flusing , bronchospasm and anaphylaxis

reactions 2. Can be present in IgA deficient babies due to anti IgA
antibodies
3. Not decreased by leukoreduction
Graft Vs Host 1. Rare in newborns, Present with fever, rash, hepatitis,
diarrhoea,pancytopenia, respiratory distress
2. Median period of manifestations - 4-6 weeks; 27 cases reported in
newborns
3. 90-100% mortality; Prevented by gamma irradiation
4. Susceptibile babies - Immunodeficiency, DVET, Extreme prematurity,
blood component from relatives

TRALI 1. Presents as respiratory distress, hypoxemia, hypotension, fever

2. CXR features of non cariogenic pulmonary oedema
3. To be differentiated from Transfusion associated circulatory overload
(TACO)
4. Vasopressor, fluid therapy for hypotension, respiratory support
5. Resolves in 48-96 hours
6. No case reported in neonates / ? under reported
T-antigen activation 1. Routine cross matching does not detect T- activation
and resulting 2. Universal screening is not recommended
hemolytic reaction 3. Washed blood products might decrease further hemolysis
4. In case of life threatening hemolysis, exchange transfusion is
indicated
5. It is very difficult to get adult blood products containing no anti-T
antibodies
INFECTIOUS RISKS

Infectious agent Risk

HIV 1 in 2.3 million

Hepatitis B 1 in 2,50,000 to 3,50,000

Hepatitis C 1 in 1.8 million

Malaria 1 in 4 million

Syphilis Virtually non existant

CMV Unknown

HTLV 1 in 6,41,000 to 9,21,000

KEY STEPS DURING THE ADMINISTRATION OF BLOOD COMPONENTS

KEY STEPS COMMENTS

Informed Informed about the risks and benefits and consent obtained
consent
Requests for As per blood bank policy, all details to be filled and signed by the senior
transfusion resident on duty
Blood samples All patients being sampled must be positively identified .The collection of the
for pre- blood sample from the patient into the sample tubes and the sample labelling
transfusion should be performed as one continuous, uninterrupted event, involving one
testing patient and one doctor only. Sample tubes should not be pre-labelled. The
request form should also be signed by the person drawing the sample
Administration All patients receiving a transfusion must be positively identified. All patient
core identifiers on the baby label must match the details on the blood
component label. Transfusion should be completed within 4 hours of leaving
the temperature-controlled storage.
Monitoring of 1. Regular visual observation throughout the transfusion episode.

the patient - Pre-transfusion pulse (P), blood pressure (BP), temperature (T) and
respiratory rate (RR). These should be taken and recorded no more than 60
minutes before starting the transfusion.

- P, BP, RR, T should be monitored 15 minutes after the start of each
component transfusion. These should be repeated 1/2 hourly
-If the patient shows signs of a possible transfusion reaction, appropriate
action taken.
- Post-transfusion P, BP and T should be taken and recorded not more than
60 minutes after the end of the component transfusion.
2. Patients should be observed during the subsequent 24 hours for late
adverse reactions.
3. DVET
- PR,BP,RR to be recorded as per the monitoring chart given in the annexure
- Mid transfusion Dx to be recorded and monitoring continued at 2 hours, 6
hours and 12 hours post transfusion
- ECG leads for signs of hyperkalemia and hypocalcemia
- Post transfusion samples to be sent for appropriate investigations as
mentioned in the monitoring chart given in the annexure

Completion of All transfusion documentation should be completed by the Junior Resident on

transfusion duty. Waste to be disposed as per regulations.
REFERENCES

1. Mehta P, Vasa R, Neumann L, et al. Thrombocytopenia in the high-risk infant. J Pediatr

1980;97:791–4.
2. Christensen RD, Henry E, Wiedmeier SE, et al. Thrombocytopenia among extremely low birth
weight neonates: data from a multi hospital healthcare system. J Perinatol 2006;26:348–53.
3. Del Vecchio A, Sola MC, Theriaque DW, et al. Platelet transfusions in the neonatal intensive
care unit:factors predicting which patients will require multiple transfusions. Transfusion
2001;41:803–8.
4. Katherine Sparger; Platelet Transfusions in the Neonatal Intensive Care Unit ,Clin Perinatol -
(2015)
5. Adapted from British Committee for Standards In Hematology
6. Baer VL, Lambert DK, Schmutz N, et al. Adherence to NICU transfusion guide- lines: data
from a multihospital healthcare system. J Perinatol 2008;28:492–7.
7. Puetz J, Darling G, McCormick KA, et al. Fresh frozen plasma and recombinant factor VIIa use
in neonates. J Pediatr Hematol Oncol 2009;31:901–6.
8. Motta M, Testa M, Tripodi G, et al. Changes in neonatal transfusion practice after 

dissemination of neonatal recommendations. Pediatrics 2010;125:e810–7
9. Motta et al , Fresh Frozen Plasma Administration in the Neonatal Intensive Care Unit Evidence-
Based Guidelines, Clinics in perinatology , 2015
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10. Giancarlo Liumbruno et al,Recommendations for the transfusion of plasma and platelets, Blood
transfusion 2009
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11. British Committee for Standards in Haematology, Blood Transfusion Task Force (J. Duguid,
Chairman): D. F. O’Shaughnessy (Convenor, Task Force nominee),Guidelines for the use of
fresh-frozen plasma, cryoprecipitate and cryosupernatant , 2004
12. Bell EF, Strauss RG, Widness JA, et al. Randomized trial of liberal versus restrictive guidelines
for red blood cell transfusion in preterm infants. Pediatrics 2005;115:1685–1691
13. Kirpalani H, Whyte RK, Andersen C, et al. The Premature Infants in Need of Transfusion
(PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high)
transfusion threshold for extremely low birth weight infants. J Pediatr 2006;149:301–307
14. Robin K Whyte, Ann L Jefferies; Canadian Paediatric Society, Fetus and Newborn Committee,
Red blood cell transfusion in newborn infants- Position Statement Paediatr Child Health
2014;19(4);213-17
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16. Ronald G. Strauss. How I transfuse red blood cells and platelets to infants with the anemia and
thrombocytopenia of prematurity. Transfusion. 2008 February ; 48(2): 209–217
17. Gottschall, JL., editor. Pediatric Transfusion. A Physician’s Handbook. 2. Bethesda, Md:
American Association of Blood Banks; 2006. Blood components: red blood cells; p. 1-17
18. Ross M Fasano, Mariam Said, Naomi C Luan, Blood component therapy for the Neonate, In:
Fanaroff & Martin’s Neonatal- Perinatal Medicine.10th edition. Elsevier; 2015. p 1345
19. Pedro A, Christenses R, Transfusion practices, In:Neonatal Hematology Pathogenesis,
Diagnosis and Management of Haematological Problems 2nd edition. Cambridge University
Press; 2013. p 303