Combined use of pretest clinical probability score and latex

Combined use of pretest clinical probability score
and latex agglutination D-dimer testing for
excluding acute deep vein thrombosis
Takashi Yamaki, MD, Motohiro Nozaki, MD, Hiroyuki Sakurai, MD, Yuji Kikuchi, MD,
Kazutaka Soejima, MD, Taro Kono, MD, Atsumori Hamahata, MD, and Kaya Kim, MD, Tokyo, Japan
Objective: Currently, the latex agglutination D-dimer assay is widely used for excluding deep vein thrombosis (DVT) but
is considered less sensitive than the enzyme-linked immunosorbent assay-based D-dimer test. The purpose of the present
study was to determine if a combination of different cutoff points, rather than a single cutoff point of 1.0 ␮g/mL, on the
latex agglutination D-dimer assay and the pretest clinical probability (PTP) score would be able to reduce the use of
venous duplex ultrasound (DU) scanning in patients with suspected DVT.
Methods: The PTP score and D-dimer testing were used to evaluate 989 consecutive patients with suspected DVT before
venous DU scanning. After calculating the clinical probability scores, patients were divided into low-risk (<0 points),
moderate-risk (1-2 points), and high-risk (>3 points) pretest clinical probability groups. Receiver operating characteristic (ROC) curve analysis was used to determine the appropriate D-dimer cutoff point for each PTP with a negative
predictive value of >98% for a positive DU scan.
Results: There were 886 patients enrolled. The study group included 609 inpatients (68.7%) and 277 outpatients (31.3%).
The prevalence of DVT in this series was 28.9%. There were 508 patients (57.3%) classified as low-risk, 237 (26.8%) as
moderate-risk, and 141 (14.9%) as high-risk PTP. DVT was identified in 29 patients (5.7%) with low-risk, 118 (49.8%)
with moderate-risk, and 109 (77.3%) with high-risk PTP scores. ROC curve analysis was used to select D-dimer cutoff
points of 2.6, 1.1, and 1.1 ␮g/mL for the low-, moderate- and high-risk PTP groups, respectively. In the low-risk PTP
group, specificity increased from 48.9% to 78.2% (P < .0001) with use of the different D-dimer cutoff value. In the
moderate- and high-risk PTP groups, however, the different D-dimer levels did not achieve substantial improvement.
Despite this, the overall use of venous DU scanning could have been reduced by 43.0% (381 of 886) if the different
D-dimer cutoff points had been used.
Conclusions: Combination of a specific D-dimer level with the clinical probability score is most effective in low-risk PTP
patients for excluding DVT. In moderate- and high-risk PTP patients, however, the recommended cutoff points of 1.0
␮g/mL may be preferable. These results show that different D-dimer levels for patients differing in risk is feasible for
excluding DVT using the latex agglutination D-dimer assay. ( J Vasc Surg 2009;50:1099-105.)
The D-dimer is a specific fragment produced during the
degradation of fibrin, and the D-dimer assay is a promising
adjunctive tool for noninvasive diagnostic management of
patients with suspected deep vein thrombosis (DVT).1 Several
studies have shown that a new rapid enzyme-linked immunosorbent assay (ELISA) is a useful test for suspected DVT,
showing high sensitivity, moderate specificity, and a high
negative predictive value (NPV). However, the technique is
time-consuming and not suitable for emergency use. In contrast, the early latex assay is considered to have insufficient
sensitivity for use in clinical practice2 and is being replaced by
newer latex assays with improved sensitivity and negative
predictive value.3-7
The clinical pretest probability score (PTP) is a useful
tool for selecting patients for further diagnostic examinaFrom the Department of Plastic and Reconstructive Surgery, Tokyo Women’s
Medical University.
Competition of interest: none.
Reprint requests: Takashi Yamaki, MD, Department of Plastic and Reconstructive Surgery, Tokyo Women’s Medical University, 8-1, Kawada-cho,
Shinjuku-ku, Tokyo 162-8666, Japan (e-mail: [email protected];
[email protected]
0741-5214/$36.00
Copyright © 2009 by the Society for Vascular Surgery.
doi:10.1016/j.jvs.2009.06.059
tion for DVT. The PTP score, developed by Well et al,8 is
calculated from clinical and historical data to stratify patients into low, moderate, and high risk of DVT. Various
combinations of pretest clinical probability scores and a
normal D-dimer test value, or even a normal D-dimer value
alone, have been suggested to be sufficiently accurate for
exclusion of venous thromboembolism (VTE).9-12 The
NPV and sensitivity of the D-dimer assay make it safe for
exclusion of thrombosis in patients with a normal D-dimer
value.
A very sensitive D-dimer assay is required to exclude
VTE when the clinical pretest probability is high, whereas a
less sensitive D-dimer assay can only exclude VTE when the
clinical pretest probability is low.13 Furthermore, the very
low specificity of the D-dimer assay requires an increased
cutoff value to reduce the incidence of false-positive results.
Latex agglutination D-dimer assays are widely used in
Japan, and NANOPIA D-dimer (Sekisui Medical Co, Ltd,
Tokyo, Japan) is a new latex-based assay with a broad
measurement range (0.5-60 ␮g/mL). Without the combined use of PTP score, the NPV for the diagnosis of VTE
reaches 100% using a cutoff value of 0.5 ␮g/mL,14 which is
similar to that of various D-dimer assays in excluding VTE
in Europe and North America.15 With an increasing num1099
1100 Yamaki et al
JOURNAL OF VASCULAR SURGERY
November 2009
ber of low-PTP patients, reducing the number of falsepositive results decreases the number of additional investigations required to diagnose or exclude VTE.
The purpose of the present study was to determine if a
combination of different cutoff points rather than the manufacturer’s recommended cutoff point of 1.0 ␮g/mL, according to the pretest clinical probability (PTP) score,
would be able to reduce the use of venous duplex ultrasound (DU) scanning in a relatively large number of patients with suspected DVT using the latex agglutination
D-dimer assay.
MATERIALS AND METHODS
Patients. Between February 2006 and February 2009,
989 consecutive referral patients with suspected DVT were
prospectively evaluated at the Department of Plastic and
Reconstructive Surgery, Tokyo Women’s Medical University Hospital. Inpatients and outpatients were included. Of
989 patients, 525 were referred from various surgical departments and 464 from medical departments. Exclusion
criteria included (1) previously diagnosed DVT, (2) DU
scan results suggesting features of chronic DVT, (3) diagnosed as having upper extremity DVT, (4) symptoms lasting ⬎1 month, (5) therapeutic dose anticoagulation instituted for ⬎48 hours before examination, or (6) clinically
suspected or confirmed pulmonary embolism, with performance of DU scanning to exclude thrombosis in the lower
limbs.
Clinical probability score. The PTP for DVT was
assessed by junior residents using a questionnaire developed by Wells et al.8 One point was added for each positive
finding and 2 points were subtracted from the total if an
alternative diagnosis as likely as, or more likely than, DVT
was found. After the PTP scores were calculated, patients
were divided into low-risk (ⱕ0 points), moderate-risk (1-2
points), and high-risk (ⱖ3 points) groups.
D-dimer assay. After the PTP score was calculated for
each patient, blood samples were collected at the clinical
laboratory department, and D-dimer testing was performed
by the examiners, who were not aware of the PTP scores. The
plasma levels of D-dimer were measured using NANOPIA, a
commercially available latex agglutination assay kit, and the
results were expressed as micrograms per milliliter. It takes 10
minutes for the assay, and all D-dimer assays were performed
by technicians who were unaware of the clinical characteristics
of the patients. Briefly, the latex agglutination assay uses latex
microparticles coated with a monoclonal antibody specific for
D-dimer. Incubation with plasma results in the formation of
macroscopic agglutinates. A positive test result is defined as a
D-dimer level ⬎1.0 ␮g/mL.
Venous DU scans. All venous DU studies were performed by one experienced physician (T. Y.) who was
blinded to the results of PTP and D-dimer testing. A color
DU scanner (LOGIQ 7 PRO; GE Yokogawa Medical
Systems, Tokyo, Japan) with a 5- to 10-MHz transducer
was used. Initially, each patient was placed supine in the
reverse Trendelenburg position at 15°. Venous DU scanning was started at the distal segment of the external iliac
Fig 1. Flow chart summarizes the diagnostic process for deep
vein thrombosis (DVT) used in the study. PTP, pretest clinical
probability score.
vein and the common femoral vein, and moved to the
femoral vein at the adductor canal. The deep femoral vein
and the anterior and posterior tibial veins were also recorded. Afterwards, the patient was placed prone with the
knee flexed at 30°, and the residual popliteal, peroneal,
gastrocnemius, and soleal veins were evaluated.16
The diagnosis of DVT was based on both noncompressibility of the vein on B-mode or no evidence of spontaneous flow on color Doppler imaging. If there was no
intraluminal defect with full venous compressibility and a
normal flow, the result was considered negative. Thrombosis was considered to be proximal if a thrombus was detected in the deep veins in the pelvis, the thigh, and
popliteal region with or without calf vein thrombosis.
Thrombosis was considered to be distal if a thrombus was
detected only in the calf veins.
Screening protocol. All the patients were stratified
into low-, moderate- and high-risk groups according to the
PTP method and underwent D-dimer testing. Patients who
had low and moderate PTP and a D-dimer concentration
within normal reference ranges required no further investigation. The remaining non-high-PTP patients with elevated D-dimer and high-PTP patients underwent a venous
DU scan at presentation. Patients with a high PTP who
showed an elevated D-dimer assay value and initial negative
scan underwent repeat venous DU scanning after 1 week
(Fig 1).17 Patients with proven DVT were monitored for at
least 3 months while receiving oral anticoagulation medication.
Statistical analysis. All data were analyzed using SPSS
16 software (SPSS Inc, Chicago, IL). The Wilcoxon nonparametric rank sum test was used to evaluate differences between
means for continuous data, and the ␹2 test was used to
evaluate differences between proportions. Analysis of variance
(ANOVA), followed by the Fisher protected least significant
difference post hoc test, was used for comparison of D-dimer
JOURNAL OF VASCULAR SURGERY
Volume 50, Number 5
Yamaki et al 1101
Table I. The pretest clinical probability score
Pretest clinical probability category
Active cancer: treatment ongoing, ⱕ6
months, or palliative
Paralysis, paresis, or recent fixed
immobilization of the lower
extremity
Recently bedridden ⬎3 days or major
surgery ⱕ 4 weeks
Localized tenderness along the
distribution of the deep venous
system
Entire leg swollen
Calf swelling by ⬎3 cm vs
asymptomatic leg (measured below
tibial tuberosity)
Pitting edema
Collateral superficial veins
(nonvaricose)
Alternative diagnosis as likely as or
more likely than DVT
Scorea
Table II. Baseline patient characteristics
No. (%)
⫹1
151 (17.0)
⫹1
150 (16.9)
⫹1
247 (27.9)
⫹1
⫹1
141 (15.9)
29 (3.3)
⫹1
⫹1
137 (15.5)
322 (36.3)
⫹1
11 (1.2)
–2
440 (49.7)
a
Low risk (ⱕ0 points), moderate risk (1-2 points), high risk (ⱖ3 points).
The examiner assesses each factor, and the score is calculated as the sum in
each patient. One point is given for every positive finding, and 2 points are
subtracted if an alternative diagnosis as likely as deep venous thrombosis is
found.8
Characteristics
No (%) or
mean ⫾ SEM
Patients, total
Age, y
Gender (% female)
Inpatients
Deep vein thrombosis
Proximal
Distal
886
64.4 ⫾ 16.0
587 (66.3)
609 (68.7)
256 (28.9)
104 (11.7)
152 (17.2)
SEM, Standard error of the mean.
Table III. Prevalence of deep vein thrombosis (DVT) by
pretest clinical probability (PTP) risk classification
Pretest clinical
probability
No. (%)
DVT frequency, No. (%)
High PTP
Moderate PTP
Low PTP
Total
141 (15.9)
237 (26.8)
508 (57.3)
886 (100)
109 (77.3)
118 (49.8)
29 (5.7)
256 (28.9)
assay means among the high-, moderate-, and low-risk PTP
groups. The Fisher exact test was used for comparison of the
sensitivity, specificity, positive predictive value (PPV), and
NPV of the D-dimer assay between the different PTP categories. Receiver operating characteristic (ROC) curve analysis
was used to determine the appropriate D-dimer cutoff point
for each PTP group with a NPV of ⬎98%. Continuous data
were expressed as mean ⫾ standard error of mean (SEM).
Statistical significance was defined as P ⬍ .05.
RESULTS
Patient characteristics. Of the 989 consecutive patients evaluated, 103 were excluded on the basis of the
criteria described in Methods. Thus, 886 patients were
eligible for this study. The numbers and proportions of the
patients in each risk category are reported in Table I.8 Of
247 postoperative inpatients, prophylaxis was pharmacologic in 129 and mechanical in 118. Surgical patients
suspected of having DVT, including leg pain, edema, or a
markedly elevated D-dimer level, were referred to our clinic
ⱕ1 week after surgery. The mean age of these patients was
64 years (range, 16-102 years). There were 587 women
(66.3%) and 299 men (33.7%). The study group included
609 inpatients (68.7%) and 277 outpatients (31.3%). Of
the 886 patients evaluated, 256 (28.9%) were found to have
DVT. DVT was proximal in 104 patients (11.7%) and distal
in the remaining 152 (17.2%; Table II).
Distribution of PTP and D-dimer assay values.
Table III summarizes the distribution of the patients with
low-, moderate-, and high-risk PTP according to the calculated clinical probability score. Of the 886 patients, 508
(57.3%) were classified as low-risk, 237 (26.8%) as moderate-
Fig 2. Value of D-dimer assay by pretest clinical probability
(PTP) risk classification. Analysis of variance for multiple comparison. *High vs low PTP, P ⬍ .0001. #High vs moderate PTP, P ⫽
.001. ¶Moderate vs low PTP, P ⬍ .0001. The error bars indicate
the standard error of mean.
risk, and 141 (15.9%) as high-risk PTP. The prevalence of
DVT increased as the PTP score progressed. In this study, 61
patients had previous VTE; of these, 37 (60.7%) were classified as low-risk, 14 (23.0%) as moderate-risk, and 10 (16.3%)
as high-risk PTP. The prevalences of DVTs were 5.41%,
57.1%, and 90%, respectively; therefore, the previous history
of VTE did not affect the PTP score.
Fig 2 shows the values of the D-dimer assay in terms of
pretest clinical probability risk classification. The mean Ddimer value was significantly higher in the high-risk PTP than
in the low-risk PTP patients (11.19 ⫾ 1.09 vs 3.12 ⫾ 0.28,
JOURNAL OF VASCULAR SURGERY
November 2009
1102 Yamaki et al
Table IV. Discriminatory power of D-dimer testing using a single D-dimer ␳ point of 1.0 ␮g/mL by pretest clinical
probability (PTP) category
Category
Sensitivity no. (%)
Specificity no. (%)
PPV no. (%)
NPV no. (%)
All patients
High PTP
Moderate PTP
Low PTP
254/255 (99.6)
109/109 (100)
117/117 (100)
28/29 (96.6)
262/628 (41.7)
3/32 (9.4)
16/120 (13.3)
243/476 (48.9)
254/620 (41.0)
109/138 (79.0)
117/221 (52.9)
28/261 (10.7)
262/263 (99.6)
3/3 (100)
16/16 (100)
243/244 (99.6)
NPV, Negative predictive value; PPV, positive-predictive value.
Table V. Sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for different D-dimer cutoff
points
Variable
All patients
PTP
High
Moderate
Low
Cutoff point ␮g/mL
Sensitivity no. (%)
Specificity no. (%)
PPV no. (%)
NPV no. (%)
2.6/1.1/1.1
248/255 (97.3)
395/628 (62.9)
248/481 (51.6)
395/402 (98.3)
1.1
1.1
2.6
109/109 (100)
117/117 (100)
22/29 (75.9)
5/32 (15.6)
18/120 (15.0)
372/476 (78.2)
109/136 (80.1)
117/219 (53.4)
22/126 (17.5)
5/5 (100)
18/18 (100)
372/379 (98.2)
NPV, Negative predictive value; PPV, positive-predictive value; PTP, pretest clinical probability.
P ⬍ .0001). Similarly, the mean D-dimer value was significantly higher in the high-risk PTP than in the moderate-risk
PTP patients (11.19 ⫾ 1.09 vs 8.25 ⫾ 0.59, P ⫽ .001).
Patients with moderate PTP had a significantly higher
D-dimer value than those with low PTP (8.25 ⫾ 0.59 vs
3.12 ⫾ 0.28, P ⬍ .0001).
Discriminatory power of a single D-dimer cutoff
point for each PTP category. The discriminatory power
of a single D-dimer cutoff point of 1.0 ␮g/mL for low-,
moderate- and high-risk PTP patients, and for the entire
study population, is summarized in Table IV. In the lowrisk PTP group, D-dimer testing provided 96.6% sensitivity
and 99.6% NPV for diagnosis of DVT. In the moderateand high-risk PTP groups, D-dimer testing achieved 100%
sensitivity and 100% NPV; however, as the PTP score
increased from low to moderate, and to high, the specificity
decreased from 48.9% to 13.3% to 9.4%, respectively.
Discriminatory power using different D-dimer cutoff points for excluding DVT. To improve the discriminatory power of the D-dimer assay, ROC curve analysis
was used to determine different cutoff points in the low-,
moderate- and high-risk PTP groups. After creating ROC
curves, cutoff points with the highest sensitivities and specificities were selected. Then NPVs of the cutoff points were
tested if they were greater than 98%. Thus, D-dimer cutoff
points of 2.6, 1.1, and 1.1 ␮g/mL were selected for these
groups, respectively. With these specific cutoff points, Ddimer testing was still able to provide ⬎98% NPV (Table
V). When the specific cutoff point for the low-risk PTP
patients were used, the specificity increased from 48.9% to
78.2% (P ⬍ .0001). In the moderate- and high-risk PTP
patients, however, the specific cutoff points did not improve the specificity (P ⫽ .711 and P ⫽ .450, respectively).
Finally, when a single cutoff point of 1.0 ␮g/mL was
used, 262 patients with a non-high PTP score and a normal
D-dimer assay required no further investigation, and thus
the use of venous DU scanning could have been reduced by
29.6% (262 of 886). With the use of specific D-dimer cutoff
points, venous DU scanning could have reduced by 44.6%
(395 of 886). Therefore, 133 additional patients could
have been excluded compared with the recommended cutoff level of 1.0 ␮g/mL accordingly.
Study outcome. Repeated DU examinations were
done in 27 patients with high-risk PTP who showed an
abnormal D-dimer test result and an initial negative venous
DU scan. After 1 week, two patients were found to have
proximal DVT and anticoagulation was applied. The remaining 25 patients had no evidence of DVT, and no
further examinations were performed. During 3 months of
follow-up, patients with proven DVT did not have any
further thromboembolic complications.
DISCUSSION
This study investigated the utility of a combination of
different cutoff points for the latex agglutination D-dimer
assay and PTP score to reduce the use of venous DU
scanning in a relatively large number of patients with suspected DVT. Our main findings were that (1) NPV for the
exclusion of DVT using a single D-dimer cutoff point of
1.0 ␮g/mL exceeded 98% in each PTP category, (2) use of
a specific cutoff point of 2.6 ␮g/mL in low-risk PTP
patients increased the specificity from 48.9% to 78.2% (P ⬍
.0001), and (3) the use of venous DU scanning would have
been reduced by 44.0% if specific D-dimer cutsoff points
had been selected.
When D-dimer testing and PTP are used for exclusion of
DVT, the outcome depends largely on the reliability of the
D-dimer test. The combination of a low PTP and a normal
D-dimer concentration can be considered a safe strategy for
excluding thrombosis and for withholding anticoagulant therapy in patients with suspected VTE.9-13,17-19 Several methods
are commercially available for measuring D-dimer concentra-
JOURNAL OF VASCULAR SURGERY
Volume 50, Number 5
tions: (1) latex agglutination, (2) microplate ELISA, (3) immunofiltration (membrane ELISA), and (4) whole-blood agglutination. Among various D-dimer tests, ELISA-based
techniques have the highest sensitivity and NPV for DVT.
The first-generation latex agglutination assays are based
on the visible agglutination of antibody-coated latex particles.
Positive samples may be serially diluted to provide a semiquantitative estimate of the D-dimer concentration. Although
these assays are rapid and easy to perform, the results are
qualitative, observer-dependent, and limited in their ability to detect minimally increased D-dimer concentrations.
The second-generation latex immunoassays use the same
basic technique as the first-generation assays but use a
photometric analyzer to provide a quantitative measure of
the D-dimer and are generally able to measure lower concentrations of D-dimer reproducibly.20
Among 556 consecutive outpatients with a suspected first
episode of DVT, Bates et al21 demonstrated a NPV of 99.7%
(95% confidence interval [CI], 98.2%-100%), a sensitivity of
98.2% (95% CI, 90.4%-100%), and a specificity of 60.4% (95%
CI, 56.1%-64.7%) for exclusion of DVT using an automated,
second-generation quantitative latex MDAD-Dimer assay
(Organon Teknika Corp, now bioMérieux, Inc, Durham,
NC). Although the prevalence of DVT was only 10%, they
also showed that 50.9% of the patients with a low or moderate
pretest probability and a negative D-dimer result could safely
be excluded from further testing. Schutgens et al22 evaluated
four new D-dimer assays and a classic ELISA in symptomatic
outpatients with suspected DVT and concluded that the Tinaquant latex assay (Roche, Mannheim, Germany) had the
highest NPV of 98%, and a high sensitivity of 99%, using a
standard cutoff value.
Another factor that could affect the discriminatory
power of studies for DVT is the cutoff value of the D-dimer
test. The sensitivity could be improved by lowering the
cutoff value, but the subsequent decrease in specificity
would lead to a large number of false-positive results. On
the contrary, D-dimer cutoff values with very high specificity provide fewer false-positive results but are less sensitive
for DVT and cannot be used to exclude the disease in all
patients. Against this background, two studies concluded
that an increased D-dimer cutoff value reduced the falsepositive rate but increased the false-negative rate. Another
study, however, demonstrated that increasing the D-dimer
cutoff value led to a rise in specificity without loss of
sensitivity.23-25
Using data from a previously published study of 571
patients, Linkins et al13 reported that varying the Ddimer cutoff values according to the PTP score would
have excluded VTE in more patients than if a single
D-dimer cutoff point had been used. In that analysis,
they found that in the high PTP score group, a D-dimer
cutoff point of 0.2 ␮g FEU mL–1 was required to achieve
a NPV of 98% or higher. Similarly, in the low PTP score
group, a D-dimer cutoff point of 2.1 ␮g FEU mL–1
achieved a NPV of 98% or higher. By using this strategy,
the number of patients with false-positive results also
dropped from 89 to 9 in the low PTP group (n ⫽ 205).
Yamaki et al 1103
Even in patients with established pulmonary embolism,
our previous study demonstrated that combination of a
specific D-dimer level with PTP score is effective for
excluding DVT in low-risk PTP patients.26
In the present study, 45.9% of patients (233 of 508)
with low PTP scores showed false-positive results when a
single cutoff point of 1.0 ␮g/mL was used. When a specific
D-dimer cutoff point of 2.6 ␮g/mL was selected for lowrisk PTP patients, the proportion with false-positive results
dropped from 45.9% to 20.5% (104 of 508), a 25.4%
change. Reducing the number of false-positive results
could decrease the number of unnecessary venous DU
scans, thus saving time and money.
These results potentially provide a new strategy for diagnosis of DVT, as demonstrated in Fig 3. Patients who have a
low PTP score and a D-dimer level of ⱕ2.6 require no further
investigation, whereas patients with a low PTP score and a
D-dimer level of ⬎2.6 undergo a single venous DU scan at
presentation. Patients who have a moderate PTP score and a
normal D-dimer level require no further investigation, and
patients who have a moderate PTP score with an elevated
D-dimer level should undergo a single venous DU scan at
presentation. Finally, patients with a high PTP score who have
an elevated D-dimer level and an initial negative scan undergo
a repeat venous DU scan after 1 week because they have quite
a high risk of DVT.
Our study had a possible limitation. Although use of a
specific D-dimer level substantially decreased the number
of false-positive results in the low-risk PTP group, it did not
improve the specificity among patients with moderate- or
high-risk PTP, leading to a relatively high percentage of
false-positive results among this group of patients. Thus,
our study suggests that the D-dimer test may have a high
NPV and a high sensitivity in patients with low PTP scores,
whereas it has low utility in patients with moderate or high
PTP scores. A larger prospective study may be required to
confirm the validity of our strategy for excluding DVT
among the general population.
CONCLUSIONS
Combination of a specific D-dimer level with the clinical probability score is an effective approach for excluding
DVT in low-risk PTP patients. In patients with moderate or
high PTP, however, the recommended cutoff point of 1.0
␮g/mL may be preferable. These results show that the use
of different D-dimer levels for patients with different levels
of risk is feasible when using the latex agglutination Ddimer assay for excluding DVT.
AUTHOR CONTRIBUTIONS
Conception and design: TY
Analysis and interpretation: TY
Data collection: MN, YK, KS, TK, AH, KK
Writing the article: TY
Critical revision of the article: TY, MN
1104 Yamaki et al
JOURNAL OF VASCULAR SURGERY
November 2009
Fig 3. Potential new diagnostic strategy for diagnosis of deep vein thrombosis (DVT) using different D-dimer levels.
PTP, Pretest clinical probability score.
Final approval of the article: TY, MN, HS, YK, KS, TK,
AH, KK
Statistical analysis: TY
Obtained funding: Not applicable
Overall responsibility: TY
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Submitted Apr 27, 2009; accepted Jun 30, 2009.