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DOI: 10.1309/AJCPGVD62LKKVDLH
Abstract
The objective was to identify the usefulness
of heparin level by antifactor Xa (anti-Xa) assay
vs activated partial thromboplastin time (PTT) or
activated clotting time (ACT) in neonates undergoing
extracorporeal membrane oxygenation (ECMO).
A retrospective record review of 21 patients in the
neonatal intensive care unit (mean ECMO initiation
age, 2 days; range, 0-4 days; male/female ratio, 1:1)
undergoing ECMO from 2006 to 2008 was performed.
Linear regression correlations between anti-Xa,
PTT, and ACT were determined by extrapolating PTT
and ACT therapeutic ranges that corresponded with the
ECMO heparin target range of 0.3 to 0.6 U/mL. Pearson
correlation coefficients between heparin levels and
PTT (0.903 to 0.984), PTT less than 40 seconds after
correction using PTT-heparinase (0.903 to 1.000),
and ACT (0.951 to 0.891) in this patient population
were widely variable.
Inconsistency of PTT and ACT therapeutic
ranges corresponding to heparin levels of 0.3 to 0.6
U/mL prompts a multifactorial approach to ECMO
management because no single laboratory test can
be used to determine appropriate anticoagulation
management.
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Right
atrium
Aorta
Heat
exchanger
Postmembrane
pressure monitor
Patient
bridge
Membrane
oxygenator
Fluids Heparin
Premembrane
pressure monitor
Venous
reservoir
O2 in
Pump
DOI: 10.1309/AJCPGVD62LKKVDLH
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Discussion
This study represents objective evidence for a commonly
held notion that adequate coagulation is difficult to maintain
for neonates undergoing ECMO. ACT and PTT are of interest
because they measure the effectiveness of heparin administration at different levels of the coagulation pathway. In addition,
they are relatively easy to measure and allow for concurrent
adjustments of the heparin assay levels. When comparisons
were made between heparin levels and PTT and/or ACT, it
was clear that neither ACT nor PTT was a perfect measurement
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Characteristic
Result
M/F ratio
Mean (range) age at initiation of ECMO (d)
Mean (range) duration of ECMO (d)
Mean SD No. of ECMO coagulation
panels performed
Primary diagnosis
Congenital diaphragmatic hernia
Meconium aspiration
Pulmonary hypertension
Sepsis
1:1
2 (0-4)
10.8 (4-23)
2.35 1.08 per day
15
4
1
1
300
250
ACT (s)
Table 1
Demographic Characteristics of 21 Neonatal Intensive Care
Unit Patients Undergoing ECMO During the 2006-2008 Study
Period
200
150
PTT (s)
Results
100
50
0
0.0
0.10
0.20
0.30
0.40
0.50
0.60
0.70
Table 2
Comparison of Coagulation Panels for 21 Patients and for the Total Group
Pearson Product Correlation
Coefficient (r) With Heparin Level
PTT (s)
ACT (s)
PTT (s)
ACT (s)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
All
101-150
86-188
74-115
96-131
71-95
108-155
98-141
97-156
91-63
100-127
72-105
94-160
91-110
93-110
106-188
108-203
82-103
97-115
100-92
82-121
112-137
88-109
95-157
86-188
70-113
96-131
71-95
108-155
98-141
97-156
91-63
123-218
72-105
88-161
81-66
93-115
106-188
108-203
81-105
97-115
100-97
82-121
185-354
90-108
208-234
228-226
235-257
205-215
205-215
213-245
212-211
199-211
213-219
208-191
224-254
219-216
227-247
233-253
246-329
226-308
226-308
216-227
221-212
204-277
169-81
208-234
0.547
0.686
0.644
0.688
0.435
0.908
0.671
0.932
0.903
0.272
0.445
0.29
0.326
0.217
0.364
0.984
0.373
0.397
0.127
0.695
0.368
0.295
0.8
0.686
0.808
0.686
0.435
0.908
0.671
0.932
0.903
0.279
0.445
0.362
0.108
0.291
0.364
0.99
0.395
0.397
0.06
0.695
1
0.364
0.234
0.058
0.512
0.142
0.361
0.517
0.01
0.292
0.163
0.092
0.464
0.466
0.361
0.289
0.477
0.783
0.126
0.272
0.123
0.891
0.951
0.095
50
0
D
ay
D 1
ay
D 4
ay
D 6
ay
D 7
a
D y9
ay
D 11
ay
D 12
ay
D 13
ay
D 14
ay
D 14
ay
D 15
ay
D 16
ay
D 17
ay
D 17
ay
18
PTT (s)
100
400
300
200
100
0
ay
D 1
ay
D 1
ay
D 2
ay
D 2
ay
D 3
ay
D 3
ay
D 4
ay
D 4
ay
D 5
ay
D 5
ay
D 6
ay
D 6
ay
D 7
ay
D 7
ay
D 8
ay
D 8
ay
9
150
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
500
ACT (s)
200
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
PTT (s)
ACT (s)
250
Heparin
300
PTT
600
Heparin
Heparin (U/mL)
PTT
Heparin (U/mL)
ACT
ACT
DOI: 10.1309/AJCPGVD62LKKVDLH
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25.00
16.01
n = 27
20.00
17.63
n = 19
11.44
n = 42
20.00
n = 15
19.28
n = 13
19.94
n=8
15.00
5.46
n = 82
10.00
5.79
n = 53
5.00
0.00
0
5.00
10
12
14
Day
References
PTT and ACT ranges corresponding to heparin levels
are quite variable, and no single laboratory test can be used
alone to monitor heparin anticoagulation. PTT is, overall,
a more reliable test than ACT; however, a multifactorial
approach must be used to provide an adequate coagulation
level for patients. In our institution, we adjust heparin dosing
to keep it within the target range; in addition, we try to keep
the prothrombin time and PTT in the desired ranges. If they
are prolonged, we transfuse appropriate blood products such
as plasma. We also aim to keep fibrinogen and antithrombin
levels within adequate ranges. If they are below the target
range, we give antithrombin concentrate to bring antithrombin
levels up and cryoprecipitate to bring fibrinogen levels up to
the target levels. We try to keep the platelet count at more than
100 103/L (100 109/L), and when the level goes down,
we administer platelets.
The significance of this study lies in whether there is a
substantial improvement in the outcomes of neonates receiving ECMO based on their coagulation during ECMO. Further
investigations of interest are whether proper anticoagulation
during ECMO has an impact on the long-term morbidity and
mortality of neonates. Baird et al8 recently conducted a retrospective review of 604 consecutive pediatric ECMO patients,
comparing the coagulation parameters for survivors with
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