THROMBOSIS RESEARCH 61; 341-348,199l 0049-3848/91 $3.00 + .OO Printed in the USA. Copyright (c) 1991 Pergamon Press pk. All rights reserved.
BRIEF
COMPARISON
COMMUNICATION
OF METHODS FROM PATIENTS
5.
Halvorsen,
Haematological
FOR DETECTING WITH VENOUS
O.H.
Research University
(Received 23.8.1990;
SOLUBLE FIBRIN THROMBOEMBOLISM
Skjansberg
and
Laboratory, of Oslo,
H.C.
Ullevil Norway
IN
PLASMA
Godal Hospital,
accepted in revised form 9.11.1990 by Editor U. Abildgaard)
INTRODUCTION
ation effect
Recently, a of soluble of fibrin
conversion method is test the
sensitive
of plasminogen commercially
by Kabi. Coa-set
and quantitative based in plasma, tissue plasminogen
fibrin on the
Studies Fibrin
to plasmin, available as
on thrombin Monomer test
the
treated was
assay for determinon the stimulatory activator catalyzed
was introduced Coa-set Fibrin plasma able to
(I).. The Monomer
have shown that detect soluble
fibrin test
at lower concentrations than did the ethanol gelation (EGT) (2) and the erytrocytes-agglutination test (FM-test) Compared to fibrinopeptide A (FPA) -determinations, (3,4). however, the Coa-set Fibrin Monomer test seemed to be a less sensitive detector of fibrin generation in vitro (4). Less is known about the ability of the Coa-set Fibrin Monomer test to detect soluble fibrin generated in vivo. The purpose of this investigation was to compare the results of the Coa-set Fibrin Monomer test with the results of the EGT, the FM-test FPA determinations in patient samples. Patients suspected having venous thromboembolism were chosen as the study lation.
Key
words:
Soluble fibrin, fibrinopeptide
Coa-set A, venous 341
Fibrin Monomer, thromboembolism.
and of popu-
Vol. 61, No. 3
SOLUBLE FIBRIN IN PLASMA
342
MATERIALS
AND
METHODS
Patients.
35
consecutive
admitted Hospital, thrombosis consent
patients
(ages
to the department and presenting
Diagnostic
with
and/or pulmonary obtained from
was
criteria
for
25-83
of
embolism, each patient
venous
years,
Internal symptoms
median
Medicine suggestive studied. were before blood
venous thrombosis (n=20) was diagnosed by The diagnosis of pulmonary embolism graphy (5). and ventilation lung on a combined perfusion or more large ventilation/perfusion mismatches patients came out with negative phlebography sampling.
Venous
years), Ullev$l venous
Informed sampling.
thromboembolism:
Deep
Blood
58 at of
blood
samples
were
ascending phlebo(n=6) was based scan, showing two (6). and
taken
Nine lung
on
of the scan.
arrival
in
the hospital. Blood was cgrefully collected from an antecubital 40 mm 9/10 needle, and immediately vein, using a Vacutainer with anticoagulant. Blood samples for FPA measurements mixed were collected prior to the other samples, into vacuum tubes containing 0.15 M
NaCl;
heparin (1000 1 volume
blood. collected
Blood into
samples vacuum
IE/ml) and anticoagulant
aprotinin (1000 KIE/ml) in solution to 9 volumes of all coagulation tests were for other tubes containing Na-citrate 0.11 mol/l in Na-citrate to 9 volumes blood. Blood was
volume 1 at 2000 x g for IO minutes at +4'C, and fibrinogen) or immediately (EGT, FM-test analysed -70bC (Coa-set Fibrin small aliquots (200-500 ~1) at Venous blood samples from 20 healthy hospital FPA). were handled identically, and used as a reference. a ratio centrifuged
Assay The
of
plasma was stored in Monomer, employees
procedures. Coa-set
Fibrin
Monomer
test
(Kabi,
Sweden)
was
performed
as
previously To see 22 samples
described (4). whether freezing of the samples influenced the results, and subsequent to freezing. The were analysed prior -7O'C for 2 hours, thawed rapidly kept frozen at samples were and analyzed within the same run as the fresh samples. at 37OC, No difference was observed between the fresh and the frozen for l-6 months at Storage of control samples sam les (fig.1). g -70 C did not influence the test results significantly (data not Consequently, in this study the plasma samples were shown). stored at -7O'C for l-6 months before analysis. The Ethanol Abildgaard sidered as
gelation test was (2). Plasma samples positive.
The Erytrocytes-agglutination performed W.Germany) was
as
performed showing test (FM-test, described
according flocculation
by
to
Godal were
and con-
Boehringer Mannheim, manufacturer. the
Vol. 61, No. 3
343
SOLUBLE FIBRIN IN PLASMA
FIG.
1
Fibrin concentrations (nmol/ l),as determined by the Coaset Fibrin Monomer test, in fresh and frozen (-70°C for 2 hours, rapid thawing at 37OC) plasma samples.
performed according to A determinations were Fibrinopeptide Nossel et al (9),with some modifications described by Skjansberg treated with bentonite according to Plasma was et al (10). Kockum (II), to remove cross-reacting fibrinogen. The upper reference limit (mean +2.5 SD) for FPA-concentrations in our laboratory was 3.6 ng/ml (10). Fibrinogen The (12). Statistical
concentrations normal range
in
were our
determined laboratory
according was 1.7
-
to Clauss 4.0 g/l.
methods.
The Wilcoxon matched pairs signed rank test was used to test the difference between fresh and frozen samples. The correlation between the results of the Coa-set Fibrin Monomer test and FPA levels was tested by calculating Spearman’s rank order correlation coefficient. A two-sided significance level of 5% was chosen.
RESULTS The results of the Coa-set Fibrin Monomer test, the EGT, the FM-test and the FPA determination in plasma samples from patients with suspected thromboembolic disease are shown in Table 1. Considering Coa-set Fibrin Monomer levels exceeding 10 nmol/l (range of the healthy volunteers O-IO nmol/l) as positive results of the Coa-set Fibrin Monomer test, 14 of the 26 patients with verified thromboembolic disease came out with a positive test. The EGT was positive in 8 patients, and the FMtest in 8 patients. FPA-concentrations were elevated in 20 of the 26 patients. Venous thromboembolism was excluded in 9 patients. One of these came out with a positive Coa-set Fibrin Monomer test, 4 had positive EGT, and none had positive FM-test. FPA-levels were
SOLUBLE FIBRIN IN PLASMA
344
eleva
ted
in
7
patients.
TABLE Coa-set (median venous number given
Fibrin
1
Monomer,
and range) thromboembolism of positive to the right
Coa-set
fibrinogen FPA and levels patients with clinically suspected and in healthy volunteers. The results of the EGT and the FM-test is in the table. in
Fibrin
Fibrinogen
FPA
monomer nmol/l Verified thromboembolism (n=26)
Vol. 61, No. 3
ng/ml
16(0-200)
EGT
FM-test
Q/l
5.3(1.8-14.4)
3.3(2.1-9.4)
8
8
Negative phlebography/ lung scan (n=9)
5(1-26)
4.1(2.3-6.7)
4.8(2.6-7.8)
4
0
Healthy volunteers (n=20)
l(O-IO)
1.7(1.0-2.8)
2.3(1.7-4.0)
0
0
FIG. The
results
of
the
EGT
Monomer limit
levels. between
The negative
Coa-set
Fibrin
Monomer
The relationship Monomer assay and set Fibrin Monomer
in
2
relation
broken and
to
Coa-set
line shows the positive results
Fibrin cut-off of the
test.
between the results of the Coa-set Fibrin the EGT is shown in fig. 2. Considering Coalevels above 10 nmol/l as positive results,
SOLUBLE FIBRIN IN PLASMA
Vol. 61, No. 3
the
accordance
EGT
was
levels The Monomer tests levels
between
51%.
By
(above 4.0 relationship test is was 80%. exceeding
the
excluding
Coa-set
g/l), between
accordance FM-test
the the
a
weak
levels
test and the fibrinogen
increased and
the
to
Coa-set
60%. Fibrin
3
The results of the FM-test Fibrin Monomer levels. The cut-off limit between negative of the Coa-set Fibrin Monomer
Only
Monomer increased
shown in fig. 3. The accordance between these All plasma samples with Coa-set Fibrin Monomer FM-test. positive 35 nmol/l, expressed a
FIG.
Monomer
Fibrin with
patients
345
correlation and
was
in relation to Coa-set broken line shows the and positive results test.
observed
FPA-levels
(rs=0.35,
between Coa-set Fibrin p=O.O4) (fig. 4).
a
FIG.
??
??
Scatter plot of reFPA-levels in lation to Coa-set Fibrin Monomer levels.
??
??
(’i 0
50
Cm-set
Fibrin
lO(l
Monomer
4
I50
(nmol/l)
200
346
SOLUBLE FIBRIN IN PLASMA
Fibrin concentrations, as Monomer test, did not correlate Among Fibrin 4.0
the 14 Monomer
patients test,
only
with 2
Vol. 61, No. 3
measured by the with fibrinogen
Coa-set Fibrin concentrations.
positive results of the had fibrinogen concentrations
Coa-set above
g/l.
DISCUSSION In this study a high degree of accordance was demonstrated between the results of the Coa-set Fibrin Monomer test and the FMtest; as reported by other investigators as well (11,12). Considerable disagreement was observed between the results of the Coa-set Fibrin Monomer test and the EGT. This might partly be explained Thus, a tests below
by the somewhat
influence higher
was observed 4 g/l.
Only a demonstrated
in
of fibrinogen levels degree of accordance patient
weak correlation between fibrin
Coa-set Fibrin Monomer may have contributed rates and distribution
to
samples
with
of borderline concentrations,
test, this, volumes
and
the
EGT
between fibrinogen
(13).
the two levels
significance as determined
could by
Several
mechanisms
FPA-levels.
such as between
on
differences FPA and
in fibrin
be the
clearence monomer
(14,15). In addition, it has not yet been proven that the concentration of soluble fibrin, determined by the Coa-set Fibrin Monomer test, corresponds to the actual level of soluble fibrin in the samples. In a recent in vitro study, a considerable discrepancy was observed between FPA-levels and Coa-set Fibrin Monomer levels (4). As FPA-determination is generally accepted as a sensitive and reliable indicator of fibrin generation in vitro, this discrepancy (4) suggested that the Coa-set Fibrin Monomer test underestimated the level of soluble fibrin in plasma. Therefore, until more studies regarding the validity of the Coa-set Fibrin Monomer test are performed, the numerical values for fibrin concentrations obtained be interpreted carefully. The Coa-set Fibrin Monomer test came the 26 patients with venous thromboembolism. far too small to draw any population was the sensitivity and the venous thromboembolism, Coa-set Fibrin Monomer
specificity results our test will
by
this
assay
out
positive Although conclusions
should
in 14 of our study regarding
of the tests for detecting seem to indicate that the give positive results more
often than both the EGT and the FM-test. However, many of the expressed Coa-set Fibrin patients with verified thromboembolism Monomer levels in the normal range, and thus, the Coa-set Fibrin Monomer Test seems of little value as a tool in the diagnosis of thromboembolic diseases. As none of the assays method (4,14,15), the plasma tell
samples which of
remained the assays
study is accepted as a reference in our true content of soluble fibrin in the Therefore, our study cannot unknown. is the more accurate indicator of true
fibrinemia.
ACKNOWLEDGEMENTS The authors for expert Cardiovascular
wish to thank Renate Ruyter and Ase-Brit and the Norwegian technical assistance, Diseases for financial support.
Andersen Council on
Vol. 61, No. 3
SOLUBLE FIBRIN IN PLASMA
347
REFERENCES 1.
WIMAN, 6. plasma by Thromb.Haem.
2.
GODAL, plasma
3.
and RANBY, M. Determination a rapid and quantitative z, 189-193, 1986.
of soluble spectrophotometric
U. Gelation and ABILDGAARD, ethanol. Scand.J.Haematol.
H.C. by
LARGO, R., intermediates
HELLER, of
erytrocytes
coated
V. the with
of
fibrin
soluble
fibrin
342-350,
3,
and STRAUB, P. fibrinogen-fibrin
fibrin in assay.
Detection of conversion
monomers.
Blood
47,
in 1966.
soluble using 991-1002,
1976. 4.
5.
6.
HALVORSEN,
S.,
Comparison plasma.
methods for detecting of in vitro study. Thrombosis
RABINOV, Thrombosis BIELLO, Patients
An
NOSSEL, Measurement Invest.
8.
9.
IO.
11.
12.
13.
SKJBNSBERG, Thrombin VOX Sang.
and
K.
in D.R. with
3257-3259, 7.
SKJBNSBERG,
PAULIN, the
Leg.
RUYTER,
R. and soluble
GODAL, fibrin
57,
489-497,199O.
Res.
Roentgen S. Arch.Surg.
Diagnosis 104,
of
H.C. in
Venous
134-144,
Radiological (Scintigraphic) Suspected Pulmonary Thromboembolism.
1972.
Evaluation
of
JAMA
257,
1987. H.L.,
54,
YUDELMANN,
I.
O.H., KIERULF, generation during 50, 33-37, 1986.
A. des
A
in
of 19,
R.E.
human
P., FAGERHOL, collection
and
et al. J.Clin.
blood.
M.K. and storage
GODAL,H.C. of blood.
radioimmunoassay S. Rapid cross-reacting fibrinogen 589-598,
Gerinnungsphysiologische Fibrinogens. Acta
WIMAN, B. and RANBY, M. A rapid soluble fibrin in plasma samples. derivatives. G. Mtiller-Berghaus Science Publishers B.V. 1986, pp. VAN WERSCH, J.W.J. Adaption test procedure for fibrin lyzer. J.Clin.Chem.Clin.Biochem.
CANFIELD,
and
of fibrinopeptide 43-53, 1974.
KOCKUM, C. and FREBELIUS, fibrinopeptide A - removal bentonite. Thrombosis Res. CLAUSS, Bestimmung
O.H.,
1980.
Haemat. and
Schnellmetode 17, 237-246,
quantitative IN: Fibrinogen
et al. 215-218.
and evaluation monomers on 2,
of with
(Eds.):
a
169-174,
ZUI-
1957. assay and
of its
Elsevier
of a chromogenic centrifugal ana1990.
MUSUMECI, \I., MARRA, R., ZAPPACOSTA, B., CARLONI, CRISTOFARI, C. Evaluation of paracoagulation plasma fibrinogen chromatography. Thrombosis Res. 132, 1980.
L. tests 17,
and by 125-
SOLUBLE FIBRIN IN PLASMA
14.
MiiLLER-BERGHAUS, pretation in in fibrinolysis. lysis,
15.
Wien
OWEN, J. cations. Thromb.Haem.
Vol. 61, No. 3
G. Fibrinopeptide values and relation to clinical data. Workshop VIIIth International Congress
their interon methods on Fibrino-
1986. Scientific The
and
Utility 62,
807-810,
Standardization of
Plasma 1989.
Committee Fibrinopeptide
CommuniAssays.
BRIEF
COMPARISON
COMMUNICATION
OF METHODS FROM PATIENTS
5.
Halvorsen,
Haematological
FOR DETECTING WITH VENOUS
O.H.
Research University
(Received 23.8.1990;
SOLUBLE FIBRIN THROMBOEMBOLISM
Skjansberg
and
Laboratory, of Oslo,
H.C.
Ullevil Norway
IN
PLASMA
Godal Hospital,
accepted in revised form 9.11.1990 by Editor U. Abildgaard)
INTRODUCTION
ation effect
Recently, a of soluble of fibrin
conversion method is test the
sensitive
of plasminogen commercially
by Kabi. Coa-set
and quantitative based in plasma, tissue plasminogen
fibrin on the
Studies Fibrin
to plasmin, available as
on thrombin Monomer test
the
treated was
assay for determinon the stimulatory activator catalyzed
was introduced Coa-set Fibrin plasma able to
(I).. The Monomer
have shown that detect soluble
fibrin test
at lower concentrations than did the ethanol gelation (EGT) (2) and the erytrocytes-agglutination test (FM-test) Compared to fibrinopeptide A (FPA) -determinations, (3,4). however, the Coa-set Fibrin Monomer test seemed to be a less sensitive detector of fibrin generation in vitro (4). Less is known about the ability of the Coa-set Fibrin Monomer test to detect soluble fibrin generated in vivo. The purpose of this investigation was to compare the results of the Coa-set Fibrin Monomer test with the results of the EGT, the FM-test FPA determinations in patient samples. Patients suspected having venous thromboembolism were chosen as the study lation.
Key
words:
Soluble fibrin, fibrinopeptide
Coa-set A, venous 341
Fibrin Monomer, thromboembolism.
and of popu-
Vol. 61, No. 3
SOLUBLE FIBRIN IN PLASMA
342
MATERIALS
AND
METHODS
Patients.
35
consecutive
admitted Hospital, thrombosis consent
patients
(ages
to the department and presenting
Diagnostic
with
and/or pulmonary obtained from
was
criteria
for
25-83
of
embolism, each patient
venous
years,
Internal symptoms
median
Medicine suggestive studied. were before blood
venous thrombosis (n=20) was diagnosed by The diagnosis of pulmonary embolism graphy (5). and ventilation lung on a combined perfusion or more large ventilation/perfusion mismatches patients came out with negative phlebography sampling.
Venous
years), Ullev$l venous
Informed sampling.
thromboembolism:
Deep
Blood
58 at of
blood
samples
were
ascending phlebo(n=6) was based scan, showing two (6). and
taken
Nine lung
on
of the scan.
arrival
in
the hospital. Blood was cgrefully collected from an antecubital 40 mm 9/10 needle, and immediately vein, using a Vacutainer with anticoagulant. Blood samples for FPA measurements mixed were collected prior to the other samples, into vacuum tubes containing 0.15 M
NaCl;
heparin (1000 1 volume
blood. collected
Blood into
samples vacuum
IE/ml) and anticoagulant
aprotinin (1000 KIE/ml) in solution to 9 volumes of all coagulation tests were for other tubes containing Na-citrate 0.11 mol/l in Na-citrate to 9 volumes blood. Blood was
volume 1 at 2000 x g for IO minutes at +4'C, and fibrinogen) or immediately (EGT, FM-test analysed -70bC (Coa-set Fibrin small aliquots (200-500 ~1) at Venous blood samples from 20 healthy hospital FPA). were handled identically, and used as a reference. a ratio centrifuged
Assay The
of
plasma was stored in Monomer, employees
procedures. Coa-set
Fibrin
Monomer
test
(Kabi,
Sweden)
was
performed
as
previously To see 22 samples
described (4). whether freezing of the samples influenced the results, and subsequent to freezing. The were analysed prior -7O'C for 2 hours, thawed rapidly kept frozen at samples were and analyzed within the same run as the fresh samples. at 37OC, No difference was observed between the fresh and the frozen for l-6 months at Storage of control samples sam les (fig.1). g -70 C did not influence the test results significantly (data not Consequently, in this study the plasma samples were shown). stored at -7O'C for l-6 months before analysis. The Ethanol Abildgaard sidered as
gelation test was (2). Plasma samples positive.
The Erytrocytes-agglutination performed W.Germany) was
as
performed showing test (FM-test, described
according flocculation
by
to
Godal were
and con-
Boehringer Mannheim, manufacturer. the
Vol. 61, No. 3
343
SOLUBLE FIBRIN IN PLASMA
FIG.
1
Fibrin concentrations (nmol/ l),as determined by the Coaset Fibrin Monomer test, in fresh and frozen (-70°C for 2 hours, rapid thawing at 37OC) plasma samples.
performed according to A determinations were Fibrinopeptide Nossel et al (9),with some modifications described by Skjansberg treated with bentonite according to Plasma was et al (10). Kockum (II), to remove cross-reacting fibrinogen. The upper reference limit (mean +2.5 SD) for FPA-concentrations in our laboratory was 3.6 ng/ml (10). Fibrinogen The (12). Statistical
concentrations normal range
in
were our
determined laboratory
according was 1.7
-
to Clauss 4.0 g/l.
methods.
The Wilcoxon matched pairs signed rank test was used to test the difference between fresh and frozen samples. The correlation between the results of the Coa-set Fibrin Monomer test and FPA levels was tested by calculating Spearman’s rank order correlation coefficient. A two-sided significance level of 5% was chosen.
RESULTS The results of the Coa-set Fibrin Monomer test, the EGT, the FM-test and the FPA determination in plasma samples from patients with suspected thromboembolic disease are shown in Table 1. Considering Coa-set Fibrin Monomer levels exceeding 10 nmol/l (range of the healthy volunteers O-IO nmol/l) as positive results of the Coa-set Fibrin Monomer test, 14 of the 26 patients with verified thromboembolic disease came out with a positive test. The EGT was positive in 8 patients, and the FMtest in 8 patients. FPA-concentrations were elevated in 20 of the 26 patients. Venous thromboembolism was excluded in 9 patients. One of these came out with a positive Coa-set Fibrin Monomer test, 4 had positive EGT, and none had positive FM-test. FPA-levels were
SOLUBLE FIBRIN IN PLASMA
344
eleva
ted
in
7
patients.
TABLE Coa-set (median venous number given
Fibrin
1
Monomer,
and range) thromboembolism of positive to the right
Coa-set
fibrinogen FPA and levels patients with clinically suspected and in healthy volunteers. The results of the EGT and the FM-test is in the table. in
Fibrin
Fibrinogen
FPA
monomer nmol/l Verified thromboembolism (n=26)
Vol. 61, No. 3
ng/ml
16(0-200)
EGT
FM-test
Q/l
5.3(1.8-14.4)
3.3(2.1-9.4)
8
8
Negative phlebography/ lung scan (n=9)
5(1-26)
4.1(2.3-6.7)
4.8(2.6-7.8)
4
0
Healthy volunteers (n=20)
l(O-IO)
1.7(1.0-2.8)
2.3(1.7-4.0)
0
0
FIG. The
results
of
the
EGT
Monomer limit
levels. between
The negative
Coa-set
Fibrin
Monomer
The relationship Monomer assay and set Fibrin Monomer
in
2
relation
broken and
to
Coa-set
line shows the positive results
Fibrin cut-off of the
test.
between the results of the Coa-set Fibrin the EGT is shown in fig. 2. Considering Coalevels above 10 nmol/l as positive results,
SOLUBLE FIBRIN IN PLASMA
Vol. 61, No. 3
the
accordance
EGT
was
levels The Monomer tests levels
between
51%.
By
(above 4.0 relationship test is was 80%. exceeding
the
excluding
Coa-set
g/l), between
accordance FM-test
the the
a
weak
levels
test and the fibrinogen
increased and
the
to
Coa-set
60%. Fibrin
3
The results of the FM-test Fibrin Monomer levels. The cut-off limit between negative of the Coa-set Fibrin Monomer
Only
Monomer increased
shown in fig. 3. The accordance between these All plasma samples with Coa-set Fibrin Monomer FM-test. positive 35 nmol/l, expressed a
FIG.
Monomer
Fibrin with
patients
345
correlation and
was
in relation to Coa-set broken line shows the and positive results test.
observed
FPA-levels
(rs=0.35,
between Coa-set Fibrin p=O.O4) (fig. 4).
a
FIG.
??
??
Scatter plot of reFPA-levels in lation to Coa-set Fibrin Monomer levels.
??
??
(’i 0
50
Cm-set
Fibrin
lO(l
Monomer
4
I50
(nmol/l)
200
346
SOLUBLE FIBRIN IN PLASMA
Fibrin concentrations, as Monomer test, did not correlate Among Fibrin 4.0
the 14 Monomer
patients test,
only
with 2
Vol. 61, No. 3
measured by the with fibrinogen
Coa-set Fibrin concentrations.
positive results of the had fibrinogen concentrations
Coa-set above
g/l.
DISCUSSION In this study a high degree of accordance was demonstrated between the results of the Coa-set Fibrin Monomer test and the FMtest; as reported by other investigators as well (11,12). Considerable disagreement was observed between the results of the Coa-set Fibrin Monomer test and the EGT. This might partly be explained Thus, a tests below
by the somewhat
influence higher
was observed 4 g/l.
Only a demonstrated
in
of fibrinogen levels degree of accordance patient
weak correlation between fibrin
Coa-set Fibrin Monomer may have contributed rates and distribution
to
samples
with
of borderline concentrations,
test, this, volumes
and
the
EGT
between fibrinogen
(13).
the two levels
significance as determined
could by
Several
mechanisms
FPA-levels.
such as between
on
differences FPA and
in fibrin
be the
clearence monomer
(14,15). In addition, it has not yet been proven that the concentration of soluble fibrin, determined by the Coa-set Fibrin Monomer test, corresponds to the actual level of soluble fibrin in the samples. In a recent in vitro study, a considerable discrepancy was observed between FPA-levels and Coa-set Fibrin Monomer levels (4). As FPA-determination is generally accepted as a sensitive and reliable indicator of fibrin generation in vitro, this discrepancy (4) suggested that the Coa-set Fibrin Monomer test underestimated the level of soluble fibrin in plasma. Therefore, until more studies regarding the validity of the Coa-set Fibrin Monomer test are performed, the numerical values for fibrin concentrations obtained be interpreted carefully. The Coa-set Fibrin Monomer test came the 26 patients with venous thromboembolism. far too small to draw any population was the sensitivity and the venous thromboembolism, Coa-set Fibrin Monomer
specificity results our test will
by
this
assay
out
positive Although conclusions
should
in 14 of our study regarding
of the tests for detecting seem to indicate that the give positive results more
often than both the EGT and the FM-test. However, many of the expressed Coa-set Fibrin patients with verified thromboembolism Monomer levels in the normal range, and thus, the Coa-set Fibrin Monomer Test seems of little value as a tool in the diagnosis of thromboembolic diseases. As none of the assays method (4,14,15), the plasma tell
samples which of
remained the assays
study is accepted as a reference in our true content of soluble fibrin in the Therefore, our study cannot unknown. is the more accurate indicator of true
fibrinemia.
ACKNOWLEDGEMENTS The authors for expert Cardiovascular
wish to thank Renate Ruyter and Ase-Brit and the Norwegian technical assistance, Diseases for financial support.
Andersen Council on
Vol. 61, No. 3
SOLUBLE FIBRIN IN PLASMA
347
REFERENCES 1.
WIMAN, 6. plasma by Thromb.Haem.
2.
GODAL, plasma
3.
and RANBY, M. Determination a rapid and quantitative z, 189-193, 1986.
of soluble spectrophotometric
U. Gelation and ABILDGAARD, ethanol. Scand.J.Haematol.
H.C. by
LARGO, R., intermediates
HELLER, of
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