Download Alteration of Coagulation and Selected Clinical Chemistry

Alteration of Coagulation and Selected Clinical Chemistry
Parameters in Patients Undergoing Open Heart Surgery
Without Transfusions
JOHN D. MILAM, M.D., STEPHEN F. AUSTIN, MT(ASCP), ROBERT F. MARTIN, PH.D., ARTHUR S. KEATS, M.D.,
AND DENTON A. COOLEY, M.D.
Milam, John D., Austin, Stephen F., Martin, Robert F.,
Keats, Arthur S., and Cooley, Denton A.: Alteration of coagulation and selected clinical chemistry parameters in patients undergoing open heart surgery without transfusions. Am J Clin
Pathol 76:155-162, 1981. Alteration of coagulation status and
certain clinical chemistry laboratory determinations of 75 adult
patients undergoing cardiopulmonary bypass procedures for
acquired heart disease was studied during and after surgery.
None of the patients was given transfusions of blood or blood
components. With hemodilution, the mean hematocrit value
dropped from 38% to 28% during the procedure. Fibrin
degradation products and euglobulin lysis time were transiently
abnormal. Factor V diminished somewhat during the procedure, whereas factors VIII and IX increased after surgery.
Clottable fibrinogen values decreased slightly, but increased
to an abnormally high value at 24 and 48 hours. Mean value
of platelet counts decreased from 194,000 to 144,000//xl immediately after surgery. Knowledge of expected deviation of
coagulation factors and certain clinical chemistry tests following open heart surgery is helpful in evaluating the status of the
postoperative patient. (Key words: Open heart surgery;
Cardiopulmonary bypass; Coagulation.)
THE PRINCIPLE OBJECTIVE of this investigation
was to define subclinical coagulation derangements and
to denote certain physiologic changes occurring as a result of open heart surgery (OHS) and/or hemodilution
procedures in a comprehensively studied group of 75
patients who did not receive transfusions. Recognition
and proper management of aberrant clotting disorders
in patients undergoing OHS depends greatly on awareness of usual or expected alterations.
Materials and Methods
Patients
The randomly selected study group consisted of 75
adult patients having OHS for acquired heart disease.
Blood transfusion was not clinically indicated or adminReceived October 22, 1980; received revised manuscript and accepted for publication January 20, 1981.
Supported in part by the Kleberg Memorial Fund and the Johnson Space Center Fund.
Address reprint requests to Dr. Milam: Department of Pathology,
St. Luke's Episcopal Hospital, Texas Medical Center, Houston,
Texas 77030.
Departments of Pathology, Cardiovascular Surgery,
and Anesthesiology, St. Luke's Episcopal Hospital
and Texas Heart Institute, and the Department of
Pathology, Baylor College of Medicine, Houston, Texas
istered before, during, or after surgery for any of the
patients. The surgical procedures performed were as
follows: aortocoronary artery bypasses (two or more),
57; mitral valve resection and aortocoronary artery bypasses, one; mitral valve resection, four; aortic valve
resection, 13. The average age was 53 years; the range
was 31 to 76 years.
Cardiopulmonary
Bypass
Technic.
Anticoagulation was achieved by intravenous administration of sodium heparin solution, 300 units/kg
body weight, with an additional 2,500 units added to
each liter of priming solution. A disposable bubble oxygenator (Harvey disposable oxygenator, Model H
200)* was utilized, with hemodilution 6 being accomplished by priming with lactated Ringer's (Hartman's)
solution—5% dextrose mixture, 20 ml/kg body weight.
Other constituents of the extracorporeal circuit included the Sarns roller pump,t Harvey cardiotomy
reservoir (Model H-500),* Swank extracorporeal filter
(Type CA-100),$ and the Texas Heart Institute custom
tubing pack.§ Systemic normothermia was maintained during surgery. Coronary artery perfusion was
not performed. At the end of the procedure, intravenous protamine sulfate (1 mg per 100 units of
heparin) was administered to neutralize the heparin.
The mean values obtained from the perfusion data of
the 75 patients show a mean age of 53 years; weight of
patient, 79 kg; flow rate, 3,910 ml/min; perfusion rate,
50 ml/kg/min; and CPB time, 57 min. Fundamental as* William Harvey Research Corporation, Santa Ana, California.
t Sarns Manufacturing Company, Ann Arbor, Michigan.
t Pioneer Filters Inc., Beaverton, Oregon.
§ Artificial Organs Division, Travenol Laboratories, Morton
Grove, Illinois.
0002-9173/81/0008/0155 $00.90 © American Society of Clinical Pathologists
155
156
MILAM ET AL.
A.J.C.P. • August 1981
Table 1. Hematology Data
Mean ± Standard
Deviation
Hemoglobin (g/dl)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
13.1
9.2
12.0
11.5
10.2
Hematocrit (%)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
38
28
35
34
30
Range of Values
Average Percentage Change
± Confidence Interval!
Tolerance Limits for
Percentage Changet
—
10.8-16.6
7.2-11.9
9.3-15.2
9.3-14.7
8.0-13.5
-30.0
-8.6
-12.0
-22.0
±
±
±
±
1.8
2.3
2.4
2.8
± 3.8
± 3.1*
± 3.7*
± 3.5*
± 3.8*
29-50
21-37
26-45
27-45
23-42
-27.6
-8.2
-11.4
-21.1
±
±
±
±
2.0
2.4
2.6
2.9
-12—
11—
9—
1—
4.4
3.0
4.0
3.8
3.4
±
±
±
±
±
0.46
0.37*
0.47*
0.43*
0.46*
3.5-5.5
2.3-4.1
2.9-5.1
3.0-4.8
2.6-4.4
-29.8
-9.1
-12.2
-22.1
±
±
±
±
1.8
2.3
2.4
2.8
-15.1—
9.6 —
6.8—
0.6 —
Mean corpuscular volume (cu fj.)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
88
90
88
88
89
±
±
±
±
±
4.6
4.6*
4.6
4.5
4.4
77-98
76-101
77-98
79-96
77-96
2.1
0.3
0.3
0.6
±
±
±
±
0.6
0.4
0.5
0.6
7—
5 4—
6—
-3
-5§
-6§
-5
Mean corpuscular hemoglobin (pg)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
30
30
30
30
30
± 1.5
± 1.5
± 1.5
± 1.5
±1.6
26-34
25-33
26-33
26-33
26-34
-0.3
0.4
0.2
0.1
±
±
±
±
0.5
0.5
0.6
0.7
4—
8—
6 6—
-4
-8§
-3§
-7§
Mean corpuscular hemoglobin
concentration (%)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
34
33
34
34
34
±
±
±
±
±
0.9
0.9*
0.9
0.8
0.9
32-36
31-36
32-36
32-36
32-36
-2.7
-0.1
-0.3
-0.7
±
±
±
±
0.8
0.6
0.6
0.8
6.6
7.0
11.4
13.5
13.0
±
±
±
±
±
1.97
2.61
3.98*
3.03*
4.20*
3.3-13.6
2.9-13.7
5.2-23.3
8.4-21.9
5.5-35.9
8.4
76.9
114.8
103.9
±
±
±
±
10.7
16.6
18.1
18.0
2-40
3-235
5-224
2-58
0.1-52
632.5
980.2
43.4
-13.9
± 253.0
± 226.7
± 52.2
± 24.8
<25->200
0-100-200
0-100-200
0-100-200
<25->200
-63.2
-63.7
-46.4
36.1
± 6.8
± 9.7
± 10.0
± 22.3
Erythrocyte count (x 106//xl)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
±
±
±
±
±
1.23
0.99*
1.26*
1.16*
1.21*
-15.6
9.7
6.7
0.0
—
—
—
—
-44.4
-26.8
-30.8
-44.0
-43
-27
-32
-44
-44.6
-27.7
-31.2
-44.8
1
4—
4—
5—
5—
-9
-4
-3§
-7
Leukocyte Count (x 103//A1)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
Plasma hemoglobin (mg/dl)
(NV: 0.5-5.0)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
9 ± 7.6
47 ± 37.6*
74 ± 47.8*
9 ± 10.1
6 ± 7.2*
Serum haptoglobin (mg/dl)
(NV: 100-200)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
118
38
36
58
137
± 50.8
± 27.8*
± 28.6*
± 37.0*
± 48.0*
94.0— - 7 7 . 1
209.5 — - 5 5 . 7
263.6— 11.2§
247.1— - 3 9 . 2
2,795 — - 3 3 §
3,194- -10
933 — - 8 9 §
342 — - 9 8
0—
50—
50 —
300 —
-100
-100§
-100
-83§
Vol. 76 • No. 2
ALTERATION OF COAGULATION DURING OHS
157
Table I.—(continued)
Mean ± Standard
Deviation
Platelet count (xl0 : 7/nl)
(NV: 150-400)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
194
119
144
156
149
±
±
±
±
±
Range of Values
58.1
45.9*
49.9*
51.1*
48.0*
80-400
44-245
61-310
70-345
73-310
Average Percentage Change
± Confidence Intervalt
—
-37.0
-23.8
-16.8
-21.2
±
±
±
±
Tolerance Limits for
Percentage Changet
—
5.8
6.6
7.4
5.8
9^
29 -*
53 ->
25 - •
-83
-76
-64§
-67
NV, normal value.
* P < 0.01 versus preoperative mean by paired / test.
t See Results section in text.
§ When distributions are non-Gaussian, a distribution independent tolerance interval
(y = 0.99, P = 0.90) is presented. With N = 75, the confidence interval estimates in
column 3 will have a confidence level very little different from 0.99, even when departures
from normality are significant.
pects of hemodilution technics and cardiopulmonary
bypass (CPB) are described elsewhere.14
were obtained by specific factor-deficient substrate
plasma procedures.2'9,10,21~23 Fibrin degradation
products (FDP) semiquantification was determined by
tanned erythrocyte hemagglutination inhibition immunoassay (TRCHII)13 and by staphylococcal clumping technic.1 Fibrinogen standards were used to estimate FDP titer. Serum osmolality was determined by
freezing point detection,tt and viscosity by water reference.7 Enzyme kinetic reactions were utilized for
erythrocyte 2,3-DPG quantitation.18
Laboratory Procedures
The following laboratory determinations were obtained prior to heparinization preoperatively, 30 min
following onset of CPB, and at one, 24, and 48 hours
postoperatively: hemoglobin; hematocrit; erythrocyte
count; mean corpuscular volume; mean corpuscular
hemoglobin; mean corpuscular hemoglobin concentration; leukocyte count; plasma hemoglobin; serum haptoglobin; platelet count; prothrombin time; activated
partial thromboplastin time; fibrinogen; euglobulin
lysis time; tanned erythrocyte hemagglutination inhibition immunoassay; staphylococcal clumping test; reptilase time; assays for factors II, V, VII, VIII, IX,
and X; total serum protein; arterial blood gases and/?H;
serum osmolality; serum viscosity; serum sodium;
serum potassium; serum calcium; serum phosphorus;
erythrocyte 2,3-diphosphoglycerate (DPG).
Basic hematologic parameters were obtained with
the Coulter Counter Model S,H and platelet counting
was performed by use of calibrated chamber and phase
microscopy4 and by an electrical impedance counter.**
Plasma hemoglobin was measured by methodology
based on peroxidase activity of hemoglobin, with
ortho-tolidine being the oxidized substrate.3 Haptoglobin semiquantitative determinations were performed
by buffered agar gel electrophoresis of the patients'
sera with known quantities of added hemoglobin.
Ortho-tolidine was used to stain the hemoglobin
bands.19Prothrombin time,21 activated partial thromboplastin time (PTT),1215 clottable fibrinogen,20 euglobulin
lysis time,511 and reptilase time8 were determined
by established technics. Coagulation factor assays
II Coulter.Electronics, Hialeah, Florida.
** Clay Adams Ultra-Flo 100 Whole Blood Counter Model No.
2510, Clay Adams, Parsippany, New Jersey.
Results
A summary of hematology, coagulation, and chemistry data appears in Tables 1-3, respectively. In the
tables, column one lists the sample arithmetic mean and
standard deviation. An asterisk indicates that the mean
value is significantly different from the preoperative
mean at the 99% confidence level (P < 0.01) by the
paired t test. Column two lists the range of the individual observations. For the 75-value sample, this corresponds to a distribution independent tolerance interval,? = 0.99, P = 0.9017 (with 99% confidence, at least
90% of a patient population having OHS under the conditions described should have values within this interval). Column three lists the average percentage change
from the preoperative value. The 99% confidencelimits
from the mean are obtained by performing the indicated
addition/subtraction17 (for example, with 99% confidence, the true average percentage decrease in hemoglobin at 30 min CPB would be between 28.2% and
31.8%). To emphasize individual patient variation in
percentage change from the preoperative value,
column four lists statistical tolerance limits, y = 0.99,
P = 0.9517 (for example, with 99% confidence, at least
95% of a patient population having OHS under the
conditions described should have a 30 min CPB hemot t Fiske Osmatic-Automatic Osmometer Model 130, Fiske Associates, Inc. Uxbridge, Massachusetts.
158
MILAM EI AL.
A.J.C.P. • August 1981
Table 2. Coagulation Data
Mean ± Standard
Deviation
Prothrombin time (sec) (NV: 12-15)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
Activated partial thromboplastin time
(sec) (NV: 24-40)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
Fibrinogen (mg/dl) (NV: 200-400)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
12 ± 0.9
—
14 ± 1.5*
12 ± 1.0*
12 ± 0.8
35 ± 5.5
—
33 ± 5.2*
33 ± 4.2*
33 ± 4.0*
282
176
237
411
557
±
±
±
±
±
76.2
46.8*
61.5*
85.6*
103.8*
Euglobulin lysis time (min) (NV: 60)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
>60
31 ± 19*
>60
>60
>60
Tanned erythrocyte hemagglutination
inhibition immunoassay (/xg/ml)
(NV: 2-10)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
3
7
14
16
±
±
±
±
Staphylococcal clumping test (/xg/ml)
(NV: 2-10)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
1
4
4
5
Reptilase time (sec) (NV: 18-22)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
Range of Values
9-14
29->300
11-17
10-15
10-14
24-51
>300
22-50
25-51
26-42
163-573
91-336
124-479
255-620
275-798
Average Percentage Change
± Confidence Intervalt
Tolerance Limits for
Percentage Changet
—
—
—
19.2 ± 3.2
7.2 ± 2.9
2.3 ± 2.4
44-> - 6
30-* -16
22 ^ - 1 7
—
"—
- 4 . 1 ± 4.8
- 3 . 7 ± 4.2
- 3 . 6 ± 4.3
-37.2
-15.2
50.3
106.0
±
±
±
±
2.5
3.5
9.5
15.5
34 ->• - 4 2
42 -> -33§
31-> - 3 8
-17-*
15 -*
146->
229->
-57
-44§
-13§
-17
>60
6->60
21->60
>60
>60
—
—
—
—
2.5
6.8*
36.8*
37.4*
0-10
0-40
0-320
0-320
—
—
—
—
±
±
±
±
1.6
5.1*
3.8*
4.9*
0-10
0-20
0-20
0-20
—
—
—
20
27
22
19
19
±
±
±
±
±
1.9
6.4*
3.3*
2.0*
1.5*
17-26
18-59
16-31
16-25
16-24
Factor II (%) (NV: 70-130)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
81
71
74
80
±
±
±
±
14.2
13.3*
12.1*
14.4
56-119
46-113
53-109
55-113
-12.6 ± 2.5
- 7 . 4 ± 3.3
- 1 . 0 ± 3.6
7 ^ -32
19-* -34
28 - • - 3 0
Factor V (%) (NV: 70-130)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
88
61
84
100
±
±
±
±
15.7
14.8*
15.9*
17.3*
52-132
26-96
40-130
56-150
-30.3 ± 4.1
- 4 . 5 ± 4.2
15.0 ± 5.9
2 ^ -63
29-> - 3 8
62 -* - 3 2
94
79
55
73
±
±
±
±
31.2
24.4*
22.7*
22.7*
31-200
28-164
21-142
31-164
-15.8 ± 3.8
-40.1 ± 5.6
-19.4 ± 7.1
14 -* - 4 6
5 ^ -85
37 - • - 7 6
Factor VII (%) (NV: 70-130)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
34.7
10.6
-2.5
-3.9
±
±
±
±
—
—
—
—
7.2
3.2
2.7
2.8
115->
36-»
19-»
18 ->
-1§
-15
-24
-26
ALTERATION OF COAGULATION DURING OHS
Vol. 76 • No. 2
Table
Mean ± Standard
Deviation
159
2.—(continued)
Range of Values
Average Percentage Change
± Confidence Intervalt
Factor VIII (%) (NV: 70-130)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
89
120
159
173
±
±
±
±
42.0
58.7*
72.6*
75.1*
37-280
33-340
55-400
42-416
44.7 ± 22.7
96.5 ± 30.0
111.2 ± 27.9
Factor IX (%) (NV: 70-130)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
77
87
93
111
±
±
±
±
25.3
26.8*
31.0*
45.2*
31-151
34-193
35-192
24-313
19.7 ± 10.4
30.7 ± 14.9
56.9 ± 21.9
83
71
• 71
73
±
±
±
±
18.7
15.8*
16.6*
16.9*
43-126
39-109
35-122
35-109
Factor X (%) (NV: 70-130)
Preoperative
1 hour postoperative
24 hours postoperative
48 hours postoperative
-'
—
—
—
-14.1 ± 2.9
- 1 2 . 9 ± 3.7
-11.1 ± 4.9
Tolerance Limits for
Percentage Changet
—
390— -59§
266 — -64§
334 — 111
—
103 — - 6 3
149 — - 8 8
231 — -118
—
9— -37
22 — -39§
28 — - 5 0
NV, normal value.
* P < 0.01 versus preoperative mean by paired I test.
t See Results section in text.
§ When distributions are non-Gaussian, a distribution independent tolerance interval
(y = 0.99, P = 0.90) is presented. With N = 75, the confidence interval estimates in
column 3 will have a confidence level very little different from 0.99, even when departures
from normality are significant.
globin value that is from 15.6% to 44.4% lower than the
preoperative hemoglobin value).
nism by which peripheral blood platelet counts diminish is not always clearly apparent. Utilization,
sequestration, premature destruction due to physical
damage, and heparin effect are very tenable considerations. Plasma hemoglobin increases to a mean level of
74 mg/dl after surgery and rapidly diminishes during the
next two days. Plasma hemoglobin rise is principally attributed to aspiration of blood from the pericardial sac
and return of blood to the oxygenator. 16 Serum haptoglobin steadily falls to a mean low level of 25-50 mg/
dl hemoglobin-binding capacity, but rises in the first
and second day postoperatively and is roughly inversely related to the level of plasma hemoglobin.
Discussion
Blood-formed
Elements
The initial and immediate intraoperative drop in
hemoglobin, hematocrit, erythrocyte count, as well as
certain other blood-formed elements, and clinical
chemistry measurements reflect the effects of hemodilution with crystalloid solutions. The mean hemoglobin and hematocrit values at 30 min following onset
of CPB were 9.2 g/dl and 28%, respectively, and when
using the previously described systems, represent
highly satisfactory levels for perfusion. Postoperatively, the mild and even moderately anemic states do
not justify homologous blood transfusion unless other
definite clinical indications exist. At 48 hours, the mean
hemoglobin and hematocrit values of the group not receiving transfusions were 10.2 g/dl and 30%; respectively. Erythrocyte indices remained essentially unchanged. The mean total leukocyte count increased
during surgery and continued to rise, with the highest
mean count at 24 hours (13,500//xl). Platelet count fell
from a normal range to a mean level of 119,000/^1
during surgery and 144,000/jtxl one hour after closure.
Considerable variation occurred in individual cases,
and postoperative levels of 61,000 and 73,000/ju.l did not
necessarily predispose hemorrhage requiring blood
transfusion. There is typically a slight drop in platelet
count between 24 and 48 hours. The exact mecha-
Coagulation
Fibrin split products (TRCHII and staphylococcal
clumping test) rise immediately after median sternotomy, virtually a routine procedure in open heart
surgery, and gradually increase during the next two
days. The PTT and prothrombin times exhibit marked
prolongation during CPB owing to heparin effect; however, these tests are unsuitable for heparin monitoring
during CPB. Following heparin neutralization, the
mean activated PTT returns to normal values, and the
mean prothrombin time is slightly longer than mean
preoperative level, which may be attributed largely to
factor V reduction. Alteration of mean factors II, V,
VII, VIII, IX, and X assays may be compared with
changes in total serum protein for estimating changes
secondary to hemodilution and blood loss as opposed to
utilization. Total serum protein drops from the base-
160
A.J.C.P. • August 1981
MILAM ET AL.
table 3. Blood Chemistry Data
Mean ± Standard
Deviation
Range of Values
Average Percentage Change
± Confidence Intervalt
Total Serum Protein (g/dl)
(NV: 6.0-7.8)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
5.8
3.9
5.1
5.5
5.4
± 0.58
± 0.39*
± 0.58*
± 0.36*
± 0.38*
4.6-7.3
2.9-4.8
3.8-6.9
4.7-6.8
4.7-6.5
Arterial blood gases (pH)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
7.44
7.37
7.36
7.42
7.46
± 0.07
± 0.05*
± 0.06*
± 0.04
± 0.04
7.29-7.69
7.24-7.49
7.19-7.50
7.34-7.52
7.37-7.55
-1.0
-1.0
-0.2
0.2
P 0l (mm Hg)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
178
169
198
91
69
62-308
62-309
62-308
35-183
28-165
3.4
18.1
-44.5
-57.9
PCOa (mm Hg)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
36
38
37
36
34
15-52
28-52
27-62
26-72
22-43
11.3
5.7
4.1
-1.7
±
±
±
±
±
54.4
61.8
64.8
35.0*
26.0*
± 6.7
± 4.9*
± 6.7
± 6.5
± 4.7
-32.0
-11.4
-4.5
-6.3
±
±
±
±
Tolerance Limits for
Percentage Changet
2.2
3.0
2.6
2.8
-14.4 12.416.015.8-
-49.5
-35.3
-25.1
-28.5
0.3
0.3
0.3
0.3
1.411.271.512.94-
-3.38
-3.27
-2.71§
-2.46
2481251716-
-72§
-89
-106
-81§
±7.7
± 7.2
± 8.7
± 8.2
89858363-
-25§
-36§
-38§
-67
±
±
±
±
16.2
13.4
7.8
5.9
Osmolality (serum) (mOsm/1)
(NV: 280-295)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
299
315
306
282
275
±
±
±
±
±
9.8
11.7*
10.7*
10.4*
7.7*
263-320
287-374
269-330
241-316
249-291
5.6
2.7
-5.4
-7.8
±
±
±
±
1.2
1.0
1.2
1.0
141070-
-4§
-5
-11§
-16
Viscosity (serum) (times water)
(NV: 1.4-1.8)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
1.5
1.4
1.4
1.4
1.4
± 0.23
± 0.30*
± 0.24*
± 0.21
± 0.18
1.2-2.4
1.1-3.3
1.2-2.4
1.1-2.4
1.3-2.3
-6.7
-3.4
-2.1
-1.1
±
±
±
±
2.5
1.8
3.1
3.0
8.3->
8.3-•
21.4 -*
25.0 -»
-23.5§
-13.3§
-23.5§
-18.8§
Sodium (serum) (mEq/1)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
139
132
137
138
135
± 3.2
± 4.0*
± 3.6*
± 3.3
± 3.7*
131-147
123-140
128-144
130-144
126-142
-5.2
-1.2
-0.6
-3.0
±
±
±
±
0.9
0.9
0.9
0.9
2^>
6^
7^
4->
Potassium (serum) (mEq/1)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
3.7
4.6
4.2
4.1
4.0
±
±
±
±
±
0.41
0.76*
0.51*
0.31*
0.33*
2.2-4.5
3.0-6.5
3.0-5.7
3.5-5.3
3.2-4.8
25.0
14.1
11.7
8.5
± 7.4
± 6.4
±4.7
± 4.8
84.4 -»
65.0 ->
40.7^
47.0 —
-34.4
-36.8
-20.0§
-30.0
Calcium (serum) (mg/dl)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
8.5
7.5
8.6
8.4
8.2
±
±
±
±
±
0.43
0.78*
0.63
0.79
0.42*
7.7-10.2
6.2-10.8
6.9-10.7
7.3-14.2
7.0-9.0
•11.8
1.0
-1.3
-3.7
±
±
±
±
10.9->
20.4 —
23.3 -»
12.0 -^
-34.5
-18.5
-25.8
-19.4
2.8
2.4
3.1
2.0
-12
-8
-8
-11
Vol. 76 • No. 2
ALTERATION OF COAGULATION DURING OHS
161
Table 3.—(continued)
Mean ± Standard
Deviation
Range of Values
Average Percentage Change
± Confidence Intervalt
Phosphorus (serum) (mg/dl)
Preoperative
30 min CPB
1 hours postoperative
24 hours postoperative
48 hours postoperative
3.0
2.5
1.8
2.9
2.2
±
±
±
±
±
0.50
0.57*
0.67*
0.52
0.55*
1.7-4.1
0.6-3.8
0.4-3.5
1.8-4.5
1.2-5.1
-17.4
-41.5
-2.7
-26.0
Erythrocyte 2,3-diphosphoglycerate
(nmol/ml RBC)
Preoperative
30 min CPB
1 hour postoperative
24 hours postoperative
48 hours postoperative
5.1
4.9
4.9
4.7
5.3
±
±
±
±
±
0.89
0.84
0.82
0.82*
0.96
3.0-7.8
3.1-7.7
2.9-8.1
2.9-7.1
3.1-8.8
-2.2
-1.9
-6.7
5.8
NV, normal value.
* P < 0.01 versus preoperative mean by paired I test.
t See Results section in text.
§ When distributions are non-Gaussian, a distribution independent tolerance interval
line value of 5.8 g/dl to 3.9 g/dl at 30 min after initiation
of CPB and to 5.1 g/dl one hour after surgery. The
aforementioned values represents reductions of 33%
at 30 min pump time and 12% one hour after surgery.
At one hour after surgery, the greatest reduction in coagulation factors was observed with factor V (31%
decrease). At one hour, factor II was reduced by 12%,
factor VII by 16%, factor X by 14%, and fibrinogen by
16%, as related to initial values, and the changes are
comparable to total serum protein reduction.
The euglobulin lysis time shortens and becomes
transiently abnormal during the procedure, but at one
hour following CPB and thereafter, the euglobulin lysis time is normal. The mean reptilase time increases
during CPB and returns to baseline values at 24 hours.
Factor VIII is significantly increased postoperatively,
probably as a result of stress. The serum osmolality
increased and serum viscosity decreased during CPB
and in the early postoperative period as a result of
hemodilution with crystalloid solutions. The serum calcium drop during surgery is also attributed to dilution
effect. Postoperative fall in serum phosphorus is regarded as secondary to carbohydrate (glucose) load of
the hemodilution crystalloid fluid. The erythrocyte 2,3DPG levels varied slightly during the study period.
Electrolytes, arterial blood gases, and pH determinations reflect physiologic balance with good oxygenation perioperatively.
The data presented demonstrate that there is mild
hemolysis and alteration of FDP titer, platelet count,
and euglobulin lysis time during CPB. Heparin is routinely administered in significant doses prior to CPB
—
±
±
±
±
—
±
±
±
±
Tolerance Limits for
Percentage Changet
—
4.6
5.4
6.7
6.0
19.4—
1.8—
63.0—
21.6-
5.3
5.1
6.2
7.0
38.5—
56.4—
35.9—
61.4—
—
-54.1
-84.7
-34.3§
-73.5
-46.8§
-38.58
-39.68
-49.8
(-y = 0.99, P = 0.90) is presented. With N = 75, the confidence interval estimates in
column 3 will have a confidence level very little different from 0.99, even when departures
from normality are significant.
to aid in preventing clotting intravascularly and in the
extracorporeal circuit. Nonetheless, there is an expected rise in FDP during open heart surgery, probably
due largely to formation of microthrombi, which are
not known to be clinically significant. The immediate
rise in FDP after median sternotomy is believed by us
to be secondary to bone marrow embolization. In other
studies24 we have demonstrated evidence of bone marrow embolization during the rapid sawing of the sternum. The procedure is the most conventional thoracotomy approach for OHS and is generally performed before heparinization. Bone marrow particles possessing
thromboplastin activity may predispose microthrombi
formation. Transient abnormal euglobulin lysis time indicated that plasmin production may reflect a compensatory mechanism or direct activation of the fibrinolytic system.
Acknowledgments. Delia Barrientes and Dona Jones provided assistance in the preparation of this manuscript. Kathy McMillan
and Susan Stansberry provided technical assistance.
References
1. Allington MJ: Fibrinogen and fibrin degradation products and
the clumping of staphylococci by serum. Br J Haematol 13:
550-567, 1967
2. Bachmann F, Duckert F, Geiger M, et al: Differentiation of the
factor VII complex. Studies on the Stuart-Prower factor.
Thromb Diath Haemorrh 1:169-194, 1957
3. Beau AF: A method for hemoglobin in serum and urine. Am
J Clin Pathol 38:111-112, 1962
4. Brecher G, Schneiderman M, Cronkite EP: The reproducibility
and constancy of the platelet count. Am J Clin Pathol 23:
15-26, 1953
5. Buckell M: The effect of citrate on euglobulin methods of estimating fibrinolytic activity. J Clin Pathol 11:403-405, 1958
162
MILAM ET AL.
6. Cooley DA, Beall AC Jr, Grondin P: Open-heart operations
with disposable oxygenators, 5 per cent dextrose prime, and
normothermia. Surgery 52:713-719, 1962
7. Frankel S, Reitman S, Sonnenwirth AC (eds): Gradwohl's clinical laboratory methods. Seventh edition. St. Louis, CV
Mosby Co, 1970, p 643
8. Funk C, Gmur J, Herold R, et al: Reptilase-R—a new reagent
in blood coagulation. Br J Haematol 21:43-52, 1971
9. Hardisty RM, Macpherson JC: A one-stage factor VIII (antihaemophilic globulin) assay and its use on venous and
capillary plasma. Thromb Diath Haemorrh 7:215-228, 1962
10. Koller F, Loeliger A, Duckert F: Experiments on a new
clotting factor (factor VII). Acta Haematol 6:1-18, 1951
11. Kowalski E, Kopec M, Niewiarowski S: An evaluation of the
euglobulin method for the determination of fibrinolysis. J
Clin Pathol 12:215-218, 1959
12. Langdell RD, Wagner RH, Brinkhous KM: Effect of antihemophilic factor on one-stage clotting tests. J Lab Clin Med 41:
637-647, 1953
13. Mertens BF, McDuffie FC, Bowie EJW, et al: Rapid sensitive
method for measuring fibrinogen split-products in human
serum. Mayo Clin Proc 44:114-120, 1969
14. Milam JD, Austin SF: Red cell salvage in open-heart surgery,
Hemotherapy in trauma and surgery. Washington DC, American Association of Blood Banks, 1979, pp 67-75
A.J.C.P. • August 1981
15. Morin RJ, Willoughby D: Comparison of several activated partial thromboplastin time methods. Am J Clin Pathol 64:241247, 1975
16. Morris KN, Kinross FM, Stirling GR: Hemolysis of blood in
the pericardium: the major source of plasma hemoglobin during total body perfusion. J Thorac Cardiovasc Surg 49:250258, 1965
17. Natrella MG: Experimental statistics, Handbook 91. US Dept of
Commerce, National Bureau of Standards, 1963
18. Nygaard SF, Rorth M: An enzymatic assay of 2,3-diphosphoglycerate in blood. Scand J Clin Lab Invest 24:399-403, 1969
19. Nerenberg ST: Electrophoresis: a practical laboratory manual.
Philadelphia, FA Davis Co, 1966, p 141
20. Okuno T, Selenko V: Plasma fibrinogen determination by automated thrombin time. Am J Med Technol 38:196-201, 1972
21. Quick AJ: Bleeding problems in clinical medicine. Philadelphia,
WB Saunders Co, 1970, p 43
22. Quick AJ: The assay and properties of labile factor (factor V).
J Clin Pathol 13:457-462, 1960
23. Stapp WF: A one stage method for the assay of antihemophilic
factor B (AHF B) with a comment on the antihemophilic factor B (AHF B) concentration in phenylindanedione (PID)
therapy. Scand J Clin Lab Invest 10:169-176, 1958
24. Wukasch DC, Malloy KP, Rubio PA, et al: Fat embolization
resulting from median sternotomy. Texas Med 71:35-41,1975