Editorial
For reprint orders, please contact [email protected]
Platelet transfusions in neonates:
questions and answers
Expert Rev. Hematol. 3(1), 7–9 (2010)
Ronald G Strauss, MD
Professor Emeritus of Pathology & Pediatrics,
University of Iowa Hospitals & Clinics,
200 Hawkins Drive, C250 GH, Iowa City,
IA 52242-1009, USA
Tel.: +1 319 338 8071
Fax: +1 319 356 0331
ronald-strauss@ uiowa.edu
“Two key questions can be raised about platelet transfusions
(PTXs) for neonates ... do sound evidence-based guidelines exist
to decide when PTX should be given? ... [and] when a PTX is
prescribed, do we know how to select and transfuse the best
available platelet product? ”
Two key questions can be raised about
platelet transfusions (PTXs) for neonates
(defined for this editorial as preterm
infants during the first month following
delivery). First, do sound evidence-based
guidelines exist to decide when PTX
should be given? The short answer is “no”.
Second, when a PTX is prescribed, do we
know how to select and transfuse the best
available platelet product? Fortunately
for this question, the answer is “yes”. The
longer, more detailed answers to these two
questions are outlined in the remainder of
this article.
Guidelines for neonatal PTXs
It is generally accepted that human neonates
have blood platelet counts within the same
normal range as older children and adults
(i.e., 150,000–450,000/µl). However,
recent data suggest a lower normal limit
of 120,000/µl for preterm neonates during the first days following birth [1] . Using
the conventional lower limit of 150,000/
µl for normal values, below 1% of term
neonates experience thrombo­c ytopenia
[2] ; whereas 20–35% of preterm neonates
admitted to a neonatal intensive-care unit
(NICU) will have blood platelet counts less
than 150,000/µl [3,4] . When only a subset of extremely low birthweight neonates
(<1000 g at delivery) were considered, 73%
had one or more platelet counts below
150,000/µl [3] . Among all thrombocytopenic preterm neonates, 25–38% will have
blood platelet counts less than 50,000/µl
(i.e., severe thrombocyto­penia) and will
probably receive PTXs [3–5] . Thus, between
2 and 8% of all preterm neonates admitted
www.expert-reviews.com
10.1586/EHM.09.64
to an NICU will receive a PTX [5] , with
extremely low birthweight neonates given
PTX much more frequently (45% in one
report [3]).
Since only one randomized controlled
trial studying PTXs in preterm neonates
has been reported [6] , the practice of neonatal PTXs is based almost entirely on
‘level 4 evidence’ (i.e., expert opinion and
reasoning), and practices vary widely [5] .
Andrew et al.’s randomized clinical trial
enrolled preterm neonates during the first
week of life and assigned them to either
a group in which PTXs were given liberally to keep the blood platelet count
within the normal range (i.e., to receive
a PTX whenever the blood platelet count
fell below 150,000/µl), or a group that
received a PTX for specific reasons related
to true thrombocytopenia (i.e., clinical
concern about bleeding or whenever the
blood platelet count fell below 50,000/
µl) [6] . Neonates who were thrombocytopenic before possible enrollment were
excluded. Since neonates in the first group
received a PTX whenever their blood
platelet count fell below the 150,000/
µl lower limit of the normal range, their
average daily platelet counts were above
200,000/µl. Neonates in the second
group were transfused at a mean platelet
count of 60,000/µl and their average daily
platelet counts were also relatively high at
more than 100,000/���������������������
µl�������������������
. There was no difference between groups in the incidence
of intracranial hemorrhage (28 vs 26%),
the primary end point of the trial. Thus,
there was no benefit in maintaining the
blood platelet count within the normal
© 2010 Expert Reviews Ltd
ISSN 1747-4086
7
Editorial
Strauss
range versus holding PTXs until thrombocytopenia developed.
Importantly, PTXs consisted of 10 ml/kg (neonate’s weight at
the time of PTXs) of unmodified platelet concentrate (i.e., taken
from the unit and directly transfused without centrifugation).
Administered using this technique, PTX resulted in an average
post-transfusion increment of approximately 100,000/µl and,
thus, no greater concentration is needed.
“It is widely agreed that the blood platelet count
should not fall below 50,000/µl in preterm
neonates who exhibit active bleeding or are at a
great risk of bleeding…”
It is widely agreed that the blood platelet count should not
fall below 50,000/µl in preterm neonates who exhibit active
bleeding or are at a great risk of bleeding (e.g., when a surgical or invasive procedure, such as a lumbar puncture, is to be
performed) [4,5] . For these neonates, many physicians elect to
give PTXs whenever the platelet count falls below 100,000/µl
and expand the definition of ‘great risk of bleeding’ to include
neonates receiving indomethacin, neonates with grade II intraventricular hemorrhage, neonates with sepsis and neonates with
necrotizing enterocolitis – decisions not supported by definitive or even highly suggestive data/information from properly
designed and conducted clinical trials [5] . Importantly, the vast
majority (>90% in one study [3] ) of PTXs are administered
prophylactically to neonates who have no evidence of bleeding.
Approximately 50% of neonatologists selected a relatively high
blood platelet count of 50,000/µl as the ‘transfusion trigger’,
for extremely low-birthweight neonates [5] despite the absence of
apparent bleeding – again, a practice not supported by definitive
data/information.
Transfusing the best platelet product
When a PTX is prescribed for a thrombocytopenic neonate, the usual goal is to increase the blood platelet count by
50,000–100,000/µl above the pretransfusion count (e.g., from
a 40,000/µl pretransfusion platelet count to a post-transfusion
platelet count between 90,000 and 140,000/µl). As has been
reported [6] – and is consistent with my own experience – this
increment can be achieved by transfusing 10 ml/kg (infant
body weight) of an unmodified platelet unit (either a platelet
concentrate prepared from a whole-blood unit or a platelet unit
prepared by an apheresis platelet collection). Routinely reducing
the volume of platelet concentrates and increasing the number
of platelets per milliliter for infants, by means of additional centrifugation steps, is both unnecessary and unwise – unless it is
specifically required.
Transfusion of 10-ml/kg platelet concentrate, taken directly from
the unit and transfused, provides approximately 10 × 109 platelets.
If the blood volume of an infant is 70 ml/kg bodyweight and the
plasma volume is 40 ml/kg, the platelet dose of 10 ml/kg can be
calculated to increase the platelet count by 100 × 109 to 150 × 109/l
above the pretransfusion baseline – assuming a post-transfusion
platelet recovery of 60%. This calculated increment is consistent
8
with the actual increment reported in human infants administered
PTX [6] . With modest thrombocytopenia, a smaller 5-ml/kg dose
may be sufficient to raise the post-transfusion platelet count to above
100,000/µl. In general, 5–10 ml/kg is not an excessive transfusion
volume for sick neonates, as long as the intake of other intravenous
fluids, medications and nutrients is adjusted. Thus, there appears
no logical reason to routinely volume-reduce/concentrate platelet
units before transfusion to infants.
In the selection of platelet units for transfusion, it is desirable
that the infant and the platelet donor be of the same ABO blood
group. It is important to minimize repeated transfusions of group
O platelets to group A or B recipients, because large quantities
of passive anti‑A or anti‑B in the plasma can lead to hemolysis. This should be easily avoided, except in the directed‑donor
situation, in which the infant may be forced to receive platelet
transfusions from an out-of-group donor (i.e., not of the identical ABO group). Hopefully, sound medical sense will prevail in
these situations, and ABO-identical platelets from the general
bloodbank inventory will be selected, rather than taking the risks
of directed donation.
“In the selection of platelet units for transfusion, it
is desirable that the infant and the platelet donor
be of the same ABO blood group.”
Proven methods exist to reduce the volume of platelet concentrates but should only be employed when it is truly warranted
(e.g., multiple transfusions anticipated from directed donors
in which several doses of passive anti‑A or anti‑B may lead to
hemolysis, or documented failure to respond to a transfusion of
10-ml/kg unmodified platelet concentrate). If volume reduction
must be carried out, additional processing should be performed
with great care. The method of reduction and the efficacy of
platelet transfusions after reduction must be validated locally
to ensure the quantity and quality of platelets (both ex vivo and
in vivo) remains after modification.
Conclusion
Many preterm neonates, particularly those with birthweight
below 1000 g, exhibit thrombocytopenia and receive PTX.
Most PTXs are administered prophylactically to nonbleeding
neonates in the belief that they are at risk of developing serious bleeding. Risks of PTXs include transmission of infectious
organisms, such as bacteria, infusion of cytokines and other
potential toxins, such as plasticizers, and transfusion reactions
– including those caused by donor antibodies to red blood cell
antigens and transfusion-related acute lung injury. Moreover,
the mortality rate of neonates given PTX is double that of nontransfused neonates – although mortality can not be directly
ascribed to PTX per se.
Accordingly, until more-definitive data are available, it seems
prudent to transfuse 10 ml/kg (infant body weight) of an
unmodified platelet concentrate to preterm neonates when any
one of the following occurs: active bleeding or definite threat
of bleeding posed by an invasive procedure/surgery and fall in
Expert Rev. Hematol. 3(1), (2010)
Platelet transfusions in neonates: questions & answers
the blood platelet count to below 100,000/µl; potential threat
of increased bleeding posed by the development of grade 2 intracranial hemorrhage, indomethacin therapy, sepsis or necrotizing enterocolitis and a fall of the blood platelet count to below
50,000/µl; when blood PTL count falls below 30,000/µl in
clinically stable neonates with no apparent increased bleeding
risks (prophylaxis).
References
1
2
Wiedmeier SE, Henry E, Sola-Visner MC,
Christensen RD. Platelet reference ranges
for neonates, defined using data from over
47,000 patients in a multihospital
healthcare system. J. Perinatol. 29,
130–136 (2009).
Dreyfus M, Kaplan C, Verdy E, Schlegel
N, Durand-Zaleski I, Tchernia G.
Frequency of immune thrombocytopenia
in newborns: a prospective study. Immune
Thrombocytopenia Working group. Blood
15, 4402–4406 (1997).
www.expert-reviews.com
Editorial
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
3
Christensen RD, Henry E, Wiedmeier SE
et al. Thrombocytopenia among extremely
low birthweight neonates: data from a
multihospital healthcare system.
J. Perinatol. 26, 348–353 (2006).
5
Josephson CD, Su LL, Christensen RD
et al. Platelet transfusion practices among
neonatologists in the United States and
Canada: results of a survey. J. Pediatr. 123,
278–285 (2009).
4
Strauss RG. How I transfuse red blood cells
and platelets to infants. Transfusion 48,
209–217 (2008).
6
Andrew M, Vegh P, Caco C et al. A
randomized, controlled trial of platelet
transfusions in thrombocytopenic
premature infants. J. Pediatr. 123, 285–291
(1993).
9