5, Zamet. P, Monset-Couchard. M, Mm- kowski. A: Evolution of bloodclotting factor levels in premature ... 19. Dube. B, Dube RK, Bhargava. V. Kolindewala.
From bloodjournal.hematologylibrary.org by guest on July 11, 2011. For personal use only.
1988 72: 1651-1657
Development of the human coagulation system in the healthy premature infant M Andrew, B Paes, R Milner, M Johnston, L Mitchell, DM Tollefsen, V Castle and P Powers
Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved.
From bloodjournal.hematologylibrary.org by guest on July 11, 2011. For personal use only.
Development
of the
Human
Coagulation
System
in the
Healthy
Tollefsen,
V.
Premature
Infant By This
M.
Andrew,
study
was
development healthy
infants
to
The
problems
and
oxygen.
weeks
did
not
were
of
90,
and
studied
thrombin
II.
kininogen
day
V.
VII.
(vWF)J
during
the
healthy
and
VIII,
IX.
first
6 months
of
infant
was
evidence of the
tune infant identified
compared problems
lishing
reference
to the
premature
in the coagulation
tests: time,
factor
assays
high-mol-wt
von
reference in the A similar
study because
that differ
in the
infant. need
fullterm
These for data
the
beyond
the
apply need
first
for the infant of the of the prema-
equally
for a large week
of life,
and the use of plasma from the infant rather than the cord day 1 values. In addition, many premature infants are which should exclude them from a study directed determining reference system
normal values in the
postnatal determine infant
The purpose a reference
infant and
the
Thus,
there
are
no
for ill, at
complete
as yet for the components of the coagulation healthy premature infant throughout the
period. such
premature
values.
with
our
of the range
previous
following and to
data
for both
II and
X only;
for
shown
for
XII.
for
adults.
plasminogen.
postnatal
all
By
of age.
6 months in
premature
components
infants.
the with
infants age
II, V. VIII.
levels
was IX,
XI.
general,
was
the
components
the
accelerated
fullterm
of the
had
was
Next,
in 1 1 8 fullterm
with
infants
set
compared
In
a PC,
data
of gestational
adult
most
was
AT-Ill.
these
factors
as compared
there of
entire
inhibitors.
towards
infants
and
for
study effect
eight
maturation
in premature
weeks
were
fibrinogen,
and
(PC).
immunologic
levels
premature
An
C
and
the
infants
published
for
HMWK.
ranges
system
those
36 for
therefore,
premature
of a previously with
to
age
reference
the
protein
of biologic 30
Powers
infants.
coagulation
achieved
near
adult
1988
by
Grune
&
Stratton,
Inc.
study was to compare the
University Medical Centre, and informed consent was obtained for all infants. The information from the premature infants was compared with the previously published normal values for I 18 healthy fullterm infants and 29 healthy adults.’ Laboratory. The techniques for obtaining blood samples, handling blood samples, and measuring the factor assays have been described in detail for the fullterm infant.’ In brief, a 2-mb blood sample was collected in the postnatal period on days 1, 5, 30, 90, and I 80. Platelet-poor plasma (PPP) was fractionated and frozen for future coagulation studies. A combination of biologic and immunologic assays was performed using previously published micro techniques.#{176} The screening tests consisted of a prothrombin time (PT; Dade C rabbit thromboplastin with an international sensitivity index of 2.5), an activated partial thromboplastin time (APT’F; Dade Actin FS) and a 2-U thrombin clotting time (TCT). The measured components of the fibrinolytic and coagulation systems included plasminogen, fibrinogen, factors II, V, VII, VIII, IX, X, XI, XII, prekallikrein (PK), high-mol-wt kininogen (HMWK), XIIIa, XIIIb, and von Wiblebrand factor (vWF). The inhibitors measured included antithrombin III (AT-Ill), hepanin cofactor II (HCII), a,-antitryp-
the fullterm
adult. From
MATERIALS
AND
METHODS
infants (30 to 36 weeks of gestational age) born at St Joseph’s Hospital or McMaster University Medical Centre in Hamilton, between December 1, 1983 and February 1, 1987 were eligible for this study. The gestational age was based on a combination of maternal dates and the Dubowitz assessment, with the latter used in cases of disagreement. The premature population was carefully screened to exclude infants who had any of the following: peninatal asphyxia, respiratory distress syndrome, oxygen support, sepsis, ventilation, or any other significant postnatal problem. In addition, infants who were small for gestational age were not recruited for this study. All infants received 1 mg vitamin K intramuscularly (IM) at birth, and the Apgar score and mode of delivery were recorded. On each study day, information regarding head circumference, crown to heel length and weight, milk formula, and medications was recorded. This study was approved by the Ethics Committee both at St Joseph’s Hospital and at McMaster Subjects.
gestational
coagulation
results
S
of con-
levels in the
infant
include
Between
of
P.
a1-
ranges fulltenm
undertaken literature system
of the
inhibitor,
used.
generate
system
Ill (AT-Ill).
a2-macroglobulin.
life.’
to
and
values.
Willebrand
to the fullterm infant.229 All previously contributing to the difficulty of estabvalues
the
following
XIII.
1 . 5,
infants
[antithrombin
we published coagulation system
factors
used
and
esterase
Castle,
A combination
effect
and
those
(PK).
inhibitors
were
minimal
20-mi
13 XII.
assays
supplemental blood
Cl S (PS)].
a
thromboplastin
Xl.
health
on days
D.M.
protein
or
of the
a2-antiplasmin.
premature
size,
X.
the
major
premature
plasminogen;
eight II.
siderable components
sample
each partial
prekallikrein
cofactor
ECENTLY, human
96
were
entered
any
period
and
for
time.
(HMWK).
heparin
40
or
premature
and
postnatal
activated
clotting
[fibrinogen. factor
each
time.
of healthy
age) have
Mitchell, antitrypsin,
the
Hospital Hamilton
ventilation
in the
in
thirty-seven
did not
Between
on
in
L.
postnatal
Joseph’s
information
1 80.
prothrombin
St
gestational
require
obtained
the system
Centre
infants
Johnston,
mothers
either
hundred
Demographic
sample
R
36
M.
determine
Consecutive at
One
premature
Milner,
coagulation
Medical
consent.
(30
study.
to
born
University for
R.
human
infant.
infants
McMaster
were
the
premature
asked
Paes,
designed
of
premature
30.
B.
Healthy
premature
Blood, Vol 72, No 5 (November),
1988: pp 1651-1657
the
Biostatistics,
Departments
Ontario,
Hamilton. ington
of
and Pathology, Canada;
University,
and
St
Louis.
Submitted
February
23,
Supported
by
Services
Pediatrics,
St
W, Rm
charge payment. “advertisement” indicate this 1 988
the
requests
McMaster
The publication
©
of
reprint
accepted
84-25
D.M.
is a scholar
Clinical
Epidemiology,
University
Department
1988;
No.
Medical
Centre,
of Medicine,
Wash-
July
from
the
7, /988. Ontario
Tollefsen
is supported
Institutes
of Health,
the National
Address
Main
Grant
Incorporated.
HL-27589from MA.
Pediatrics, McMaster
Heart
Ontario to
M.
University
Physician by
Grant
No.
Bethesda,
MD.
Foundation.
Andrew, Health
MD, Sciences
Department
of I 200
Centre,
3N27, Hamilton, Ontario L8N 3Z5, Canada. costs ofthis article were defrayed in part by page This article must therefore be hereby marked in accordance
with
18 U.S.C.
section
1 734 solely
to
fact.
by Grune
& Stratton,
Inc.
0006-4971/88/7205-0016$3.00/o
1651
From bloodjournal.hematologylibrary.org by guest on July 11, 2011. For personal use only.
ANDREW
1652
Table
1 . Demo graphic
Data
of Study
No.
ion: Postnatal
Populat
Age
of Infants
Born
Weeks
at 34-36
of Gestation
1
5
30
90
70
49
27
28
ET AL
al Age (Days) 180 24
Weight(kg)
2.16
±
0.35
2.03
±
0.29
3.05
±
0.73
5.10
±
1.03
7.03
±
Headcircumference(cm)
32.6
±
1.4
31.4
±
1.4
34.5
±
2.1
39.5
±
42.5
±
1.0
Length(cm)
45.4
±
3.0
45.6
±
2.8
47.8
±
4.2
54.2
±
3.5 4.8
64.2
±
3.1
sin (a,-AT), a2-antiplasmin (a2-AP), a2-macroglobulin (a2-M), C1 esterase inhibitor (C,INH), protein C (PC), and protein S (PS). For each component measured, change due to gestational age between 30 and 36 weeks was assessed using both a linear analysis and a two-way analysis of variance (ANOVA) with repeated measures comparing mean values of infants from 30 to 33 weeks to those of 34 to 36 weeks at all postnatal time points. The premature data were then amalgamated into one data set, and each component measured in the premature infant was compared with previously published data for the fulbterm infant’ by measuring the change in mean values over time in the postnatal period using a two-way ANOVA with repeated measures. Specific differences between the premature and fublterm infant were then tested using Student’s test. For the latter, because of the use of up to five comparisons, P values