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194 Chapter 18 Diagnostic algorithms for acute deep venous thrombosis and pulmonary embolism
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initial examination, although this has not been clearly
validated.
examinations will be negative, proving this method to be
both costly and time-consuming.
15,20
Additionally, the vast majority of repeat US
3
Further studies have examined the role of combining D-dimer and ultrasonography to reduce the number
of repeat US examinations required. Those patients with
a negative D-dimer assay and a negative initial US were
noted to have a thromboembolic complication rate of
1.3% in 3 months of follow-up, a rate that is comparable
to repeat sonography at a greatly reduced cost and time
commitment.
be employed, but only in those with positive D-dimer tests
and negative initial US.
19,21
In these situations, repeat US should still
19,22
Supercial venous reux disease has been treated with
endovenous ablation techniques for more than 15years.
Thrombi discovered in the postoperative period are
referred to as endovenous heat-induced thrombi (EHIT).
Very few studies have looked at the US differentiation
between EHIT and spontaneous thrombosis.
23
Radiofrequency ablation results in vein occlusion by
inducing vein wall collagen contraction through heat-induced denaturation of the collagen matrix, followed by
brosis, with sealing of the vessel lumen due to injury and
inammation of the vein wall.
24
Secondary methods of vein closure include endothelial
denudation, which is swelling of the vein wall components
due to heat-induced inammatory processes that occur
as responses to temperature gradients created during the
treatment from the intima to the adventitia.
The total injury to the vein wall collagen, and subsequently the total shrinkage of the vein wall, is determined
by the intima to the adventitial temperature gradient and
the duration of the time of heating. Laser venous-induced
injury is caused by steam bubbles. With both techniques,
the thrombus appears different on venous duplex and
pathologically than with a spontaneous thrombosis.
23,25
It is important to differentiate de novo thrombi from
EHIT in the development of a treatment algorithm in
patients who have undergone endovenous ablations.
Thrombi that are associated with ablation techniques have
a greater degree of hypercellular response, a broblastic
reaction, and edema. De novo thrombi have a more prolic
response to trichrome staining pathologically. In an experimental study by Santin etal.,
23
evidence of neovascularization was found in all EHIT specimens, but only in 33% of
de novo thrombi. While it may be possible histologically
to differentiate the source of thrombus on US, this can be
difcult.
23
The EHIT is more hyperechoic with less venous
distention and less compressibility. It has more echogenicity than the de novo thrombus on US scanning.
Post-treatment duplex scans should report the extent
of thrombus from the supercial vein into the deep vein,
whether this is at the saphenofemoral or saphenopopliteal junction. The degree of extension must be reported, as
this will be used in the determination of treatment. Those
causing less than 50% occlusion may be treated conservatively with observation and sequential scanning, while
those treated with greater than 50% occlusion can be
managed expectantly with short-term anticoagulant ther-
25–27
apy.
Totally occlusive thrombi are treated as a DVT
(Figures18.2–18.6).
18.2 Ideal duplex image after radiofrequency ablation. Vein
occluded without thrombus extension into the common femoral
vein (CFV). A: artery; CSI: conuence of the supercial inguinal
veins; TA: total occluding acute; W/C: with compression.
Source: (From Lohr J, Kulwicki A. Semin Vasc Surg 2010;23:90–100. With
permission.)
18.3 Compressed hyperechoic image.
18.4 Flush occluded saphenofemoral junction endovenous
heat-induced thrombus.
Pitfalls in venous duplex imaging include misidentication of veins, duplicated vein systems, systemic illness
or hypovolemia decreasing venous distention, suboptimal imaging in obese or edematous patients, or areas
not amenable to compression, such as the iliac veins and
18.5 Protruding endovenous heat-induced thrombus.
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18.1 Introduction 195
As with most studies involving DVT in the lower extremities, the sensitivity of MRV decreases the more peripherally
a thrombus is located. In a prospective, blinded study, MRV
direct thrombus imaging had sensitivity values of 94% or
96%, depending on the reader.
30
When isolated calf DVTs
were examined, the sensitivity values of MRV were 83%
and 92% for the two readers. For DVT involving the femoropopliteal segment, sensitivities were signicantly higher
at 97% for both readers. When the iliofemoral segment
was examined, sensitivity rose to 100% for both readers.
An additional benet that MRV may share with CUS
is in the aging of thrombi. In a comparison study of
venous-enhanced subtracted peak arterial MRV to CV,
100% sensitivity and specicity values for DVT in the iliac
and femoral veins were noted.
31
Interestingly, vessel wall
enhancement was noted for acute thrombosis but not for
chronic thrombosis.
Tempering the enthusiasm for MRI/MRV are the time
requirements and patient cooperation needed to perform
the study. Using MRV to diagnose DVT might limit the
availability of MRI for other uses due to scheduling difculties. In addition, patients with certain implants may
not be able to undergo testing. Lastly, the cost of MRV is
signicantly higher than most other DVT studies. In one
study, MRV’s cost was 1.4 times that of CV and 2.5 times
that of duplex scanning.
28
Recently, concerns have been raised regarding the
safety of gadolinium in patients with renal insufciency.
There is evidence to suggest that gadolinium is associated
with nephrogenic systemic brosis.
32–35
18
18.6 Free-oating endovenous heat-induced thrombus tip in
common femoral vein.
adductor canal. As with most US-based imaging studies,
the quality of the examination depends largely on the technician performing the examination.
18.1.6 Magnetic resonance imaging/MRV
Magnetic resonance imaging (MRI)/MRV, as discussed in
detail in Chapter16, has gained momentum in recent years
for the detection of DVT. In addition to being less invasive
than CV, MRV overcomes some of the limitations of CUS
and IPG. Since MRV directly visualizes the thrombus, even
non-ow-limiting thrombi should be detectable, in contrast
to IPG. MRV should also be able to detect thrombi proximal to the inguinal ligament, an area that has been problematic for CUS in the past. Furthermore, MRV results are
also independent of the technologist’s experience and availability, in contrast to CUS.
When Carpenter etal. compared MRV to CV, the results
were identical in 97% of the patients scanned.
the extent of the thrombus and whether it was partially or
totally occlusive was in complete agreement between the
two studies. MRV had a sensitivity and specicity of 100%
and 96%, respectively. Similar results were noted by Laissy
etal., with MRV demonstrating 100% sensitivity and specicity compared to CV.
29
MRV was, once again, noted to
have a high sensitivity of 95% for detecting the extent of
the DVT.
28
In fact,
18.1.7 D-dimer
Using D-dimer to preselect patients who are likely to have
DVT has gained considerable interest in an effort to reduce
costs and expedite patient workup. The D-dimer assays
currently available include turbidimetry, enzyme-linked
immunosorbent assay (ELISA), latex particle agglutination,
uorescence immunoassay, and immunoltration tests.
Each assay has a corresponding normal reference range,
which is typically not interchangeable.
A combination of the Wells pretest clinical probability (PCP) score and quantitative D-dimer testing was used
by Yamaki et al. to reduce the number of venous duplex
scans performed.
ative predictive value (NPV) were noted in the study. The
authors recommended no further testing to rule out DVT
in patients with low-to-moderate PCP and a negative D-dimer test. This recommendation reects the ndings of
previous studies in which the NPV of D-dimer using the
SimpliRED assay decreased from 94.1% in the moderate
PCP group to 86.7% in the high-probability patients.
Asystematic review by Fancher etal. and a meta-analysis by Wells etal. concluded that DVT could effectively be
ruled out in patients with low-to-moderate clinical probability and a negative D-dimer assay.
D-dimer levels in patients without a PCP score were
measured by Diamond et al.
ing, the D-dimer results revealed 100% sensitivity and
100% NPV, but only 48.8% specicity due to the large
number of false positives. It was estimated that 42% of the
venous duplex studies could have been eliminated based on
36
A100% sensitivity and a 100% neg-
6,38
39
Compared to duplex imag-
37
196 Chapter 18 Diagnostic algorithms for acute deep venous thrombosis and pulmonary embolism
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D-dimer assay alone. Five different quantitative D-dimer
assays were compared by Stevens etal., and the NPV was
uniformly high as long as the cutoff level for the D-dimer
assays was set for high sensitivity.
the study is maintained even in the presence of cellulitis.
40
The high sensitivity of
41
In a review by Goodacre etal. of 97 studies, the sensitivity and specicity of the D-dimer assays were observed
to vary widely.
15
The post hoc thresholds yielded higher
sensitivity since levels that maximize sensitivity were probably chosen, and the use of D-dimer in patients with low
clinical probability was likely to yield a higher specicity
secondary to the lower number of false positives.
There are situations where the D-dimer assay may produce false positives. These situations include pregnancy,
malignancy, recent postoperative state, and total bilirubin
greater than 2 mg/dL. Further confounding factors may
include the age of the clot (as signicant declines in the
D-dimer level may occur with time), position of the clot
(isolated calf DVT reduces sensitivity), and heparin use
(which may signicantly reduce D-dimer levels).
42
Despite
its limitations, D-dimer is a useful tool for ruling out DVT
as long as the threshold is set low enough to keep the sensitivity high. If a higher specicity is desired, the D-dimer
assay should be used in conjunction with a PCP score.
18.1.8 Additional studies
Studies examining other diagnostic modalities, including
computed tomography (CT), liquid crystal contact thermography, C-reactive protein, rheography, and photoplethysmography, have been performed with varying degrees of
success.
43–48
At this time, however, none of the alternative
imaging modalities have achieved mainstream status, limiting their usefulness in the clinical setting.
18.1.9 DVT in pregnancy
Pregnancy in itself is a risk factor for the development of
VTE with a reported incidence that is 4–50 times higher
compared to nonpregnant women. Thrombotic risk is
highest in the rst 6 weeks postpartum, and although the
risk persists to 12 weeks, the absolute risk beyond 6 weeks
appears to be low. The diagnosis of DVT during pregnancy
adds another level of complexity. There are the obvious
concerns for the well-being of the fetus, as well as questions regarding the diagnostic accuracy of DVT studies
during this period. Left-sided DVTs are much more common (90%) than right-sided DVT during pregnancy due
to the long course of the left iliac vein behind the gravid
uterus. Pelvic venous thrombosis is also increased in pregnancy.
The amount of ionizing radiation the fetus would be
exposed to during VTE workup is only considered signicant in the induction of malignancy.
received during DVT workup would be less than the background radiation received during the 9 months of pregnancy. The contrast agent may pose a risk of anaphylaxis,
in addition to crossing the placenta and possibly suppressing thyroid function in the fetus.
US remains the front-line study for detection of DVT in
pregnancy. If the quality of the US study is suboptimal or
there is suspicion of pelvic thrombus, MRI/MRV should
49
Even then, the dose
49
be considered. D-dimer levels have been known to increase
even during the course of a normal pregnancy and are
of unproven usefulness.
42
Serum D-dimer levels increase
during the course of pregnancy, with a slow decline postpartum. Using higher cutoff values may maintain high
sensitivity and improve specicity, but validation in prospective studies is needed. Anegative test, when present,
can signicantly lower the clinical suspicion of DVT, however. The decision can then be made to avoid further testing. In pregnant patients, repeat US is recommended if the
initial scan is negative for DVT.
18.1.10 Intravenous drug users
This group poses special challenges for the diagnosis of
DVT. These patients will frequently have a positive D-dimer assay secondary to infection. Furthermore, on duplex
scanning, chronic vein wall changes may be present as well.
Anegative initial scan in this group should be followed up
with a repeat study in 7–10 days, although compliance is
frequently problematic.
18.1.11 Controversies
The role of unilateral venous scanning has been greatly
debated. The Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL) has acknowledged
the need for unilateral or limited scans and published
revised guidelines. However, the frequency and importance of nding thrombi in the asymptomatic limb are
unresolved.
50–52
Ultimately, the diagnosis and treatment of
DVT continue to evolve. Even the nomenclature of veins
has evolved. Among the changes are the renaming of the
supercial femoral vein as the femoral vein, the greater/
long saphenous vein as the great saphenous vein, and the
lesser saphenous vein as the small saphenous vein in an
effort to more accurately reect their true anatomy.
53
Measurement of blood biomarkers remains under
investigation but promising. D-dimer and brinogen are
markers of hemostasis. D-dimer is a degradation product
generated during brinolysis, and levels are elevated in the
setting of active clot formation and turnover. This has been
incorporated into a diagnostic algorithm used to identify
patients with VTE. Further investigation and studies are
underway.
Baseline PTT elevations may indicate a circulating
inhibitor. These patients may have an unrecognized anticardiolipin antibody or lupus anticoagulant circulating.
This may be your only tip-off to a potential DOAC failure.
All VTE and PE patients need a baseline PTT in addition to
CBC, PT, and INR prior to selecting anticoagulant therapy
and management strategies. This may save a life and help
avoid a dreaded DOAC failure.
18.2 PULMONARY EMBOLISM
18.2.1 Background
As is the case with DVT, PE is a diagnosis that must be
conrmed through objective testing. The nonspecic signs
and symptoms of PE in association with risk factors are
Suspected acute PE
https://t.me/med1917
18.2 Pulmonary embolism 197
Clinical assessment/probability
Low probability
D-Dimer
Negative
No treatment
Negative Positive
No treatment
• Repeat CT angio or CTV/CTA if poor quality
• If CT angio only, US or MRV
• Pulmonary scintigraphy
• Digital subtraction angiography
• Serial US
Positive
CT angio vs.
CTV/CTA
Segmental or
subsegmental
Negative
No treatment
Main or lobar PE
Treatment
Moderate probability
D-Dimer
NegativePositive
No treatment
Option if CT angio only,
US or MRV
Positive
CT angio vs.
CTV/CTA
Treatment
• Repeat if poor quality
• If CTA only, US or MRI
venography
• Pulmonary scintigraphy
• Digital subtraction
angiography
• Serial US
High probability
CT angio vs. CTV/CTA
PositiveNegative
Treatment
18.7 Algorithm for the diagnosis of pulmonary embolism. CT: computed tomography; CTA: computed tomographic angiography;
CTV: computed tomographic venography; MRI: magnetic resonance imaging; MRV: magnetic resonance venography; PE: pulmonary embolism; US: ultrasound.
18
insufcient to allow for a denitive diagnosis and should
prompt the clinician to further investigate.
54
The importance of correct diagnosis and timely treatment cannot be
overstated, as the mortality after PE is much higher than
with DVT alone.
55
Figure 18.7 displays the algorithm
described in the following sections.
18.2.2 Signs and symptoms
The most common signs of PE are tachypnea and tachycardia. Less common signs, including syncope, hypoxemia,
and sudden hypotension, are also associated with PE. However, all of these signs are nonspecic and can be found in
other illnesses or conditions as well. The symptoms of PE
range widely and include anxiety, dyspnea, pleuritic chest
pain, and lightheadedness.
56
Although it appears that the
ability to accurately determine the pretest probability of PE
increases with experience, the difference is not sufciently
large, and almost a quarter of patients with PE will have
sudden death as the rst clinical presentation.
55,57
18.2.3 Clinical probability scoring
The use of a validated pretest probability score is recommended as the rst step in the workup of patients suspected
of having PE.
and expedient way to stratify patients into low/intermediate/high-probability or unlikely/likely groups, depending
on the assessment tool employed. Based upon the results,
patients should then undergo additional testing to conrm/
58
Calculating the PCP is both a cost-effective
exclude the diagnosis of PE. Used appropriately, the scoring system can reduce the need for imaging studies and
associated costs.
In a study that reviewed the Wells simplied score,
Geneva score, and empirical assessment, the authors
concluded that all three methods were clinically useful,
although empirical assessment tended to classify fewer
patients as having low probability.
58
It is the low/moderate-probability group that is of particular interest, since
this group of patients can have a diagnosis of PE effectively
ruled out with an adjunctive study.
ical decision rule shown in Table18.2,
unlikely probability and a normal D-dimer test resulted in a
subsequent VTE rate of only 0.5% in untreated patients.
Other validated scoring systems, like the one in
Table18.3, have proven similarly useful.
59,60
Using the Wells clin-
61,62
a combination of
59
63
18.2.4 Ventilation–perfusion scintigraphy
Prior to the widespread use of spiral CT (s-CT), ventilation–perfusion (VP) scintigraphy was often the rst-line
study. VP scintigraphy is less invasive than pulmonary
angiography, and a normal study can effectively exclude
PE. Apositive study is also highly specic for PE, allowing for directed treatment.
shortcomings of VP scintigraphy is the high number of
intermediate-probability scans. As noted in the Prospective
Investigation of Pulmonary Embolism Diagnosis (PIOPED)
study, up to 70% of VP scans are nondiagnostic and require
additional studies.
64
In addition, the sensitivity of VP scans
64
However, one of the major
198 Chapter 18 Diagnostic algorithms for acute deep venous thrombosis and pulmonary embolism
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TABLE 18.2 Wells Short Clinical Score list for pulmonary embolism
Criteria Score
Clinical signs and symptoms of deep venous thrombosis: minimal swelling of the leg and pain on palpation of the deep
leg veins
Pulmonary embolism more likely than an alternative diagnosis 3.0
Heartbeat frequency >100 beats per minute 1.5
Recent immobilization or surgery within <4 weeks 1.5
Documented history of deep venous thrombosis and/or pulmonary embolism 1.5
Hemoptysis 1.0
Recent history of malignancy <6 months (treatment or palliative treatment) 1.0
a
Clinical score for pulmonary embolism: low=≤2; moderate=2.0–6.0; high=≥6.
Source: From Michiels JJ etal. Semin Vasc Med 2002;2(4): 345–51. With permission.
3.0
TABLE 18.3 Antwerp Clinical Score list for pulmonary embolism
Criteria Score
Age >60years 0.5
One or more risk factors for venous thromboembolism 1.5
One or more eliciting circumstances for venous thromboembolism 1.0
Respiratory signs and symptoms
Dyspnea 1.5
Pleuritic pain 1.0
Nonretrosternal, nonpleural chest pain 1.0
PaO
<92% (<3 L O2) 1.0
2
Hemoptysis 1.0
Pleural rub 1.0
Cardiac and other signs and symptoms
Heartbeat frequency >100 beats per minute 1.0
Temperature <37.5°C and >38.6°C 1.0
Chest X-ray: atelectasis and/or unilateral diaphragm elevation suspicious for pulmonary embolism and no other explanation 1.0
62
Leg symptoms suspicious of deep venous thrombosis (swelling, pain, etc.) (clinical score of Wells et al.
thrombosis)
Signs of circulatory and/or of respiratory insufficiency: 1, 2, or 3 6.0
1. Hypotension (systolic BP <90 mmHg and heartbeat frequency >100 beats per minute)
2. Respiratory insufciency (articial breathing >3 L O
3. Recent decompensation cordis, right
a
Clinical score for pulmonary embolism: low=<3; moderate=3.0–6.0; high=>6.
Source: From Michiels JJ etal. Semin Vasc Med 2002;2(4): 345–51. With permission.
Abbreviations: PaO2: arterial partial pressure of oxygen.
)
2
for deep venous
3.0
a
a
is suboptimal. In patients with PE, the results of VP scans
are of high probability in only about 40%. The majority of
patients with PE will have intermediate- or low-probability
65
results.
There have been subsequent attempts to improve on
the diagnostic capability of VP scans. In the Prospective
Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED), only perfusion scans were performed
after patients were assigned a clinical probability.
the combined approach, a positive predictive value of
66
Using
92%–99% and an NPV of 97% was obtained. Other studies have examined VP scans in conjunction with s-CT and
noted improvements in the diagnostic performance.
67–69
VP scintigraphy may still be the rst-line study in
patients with contraindications to iodinated contrast due
to dye allergy or renal insufciency. Furthermore, the
higher radiation exposure with s-CT in young women
may be of clinical signicance.
of the PIOPED II investigators recommended pulmonary
scintigraphy over CT angiography.
70
In pregnant women, 69%
59
18.2 Pulmonary embolism 199
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18.2.5 Pulmonary angiography
Long considered the gold standard for diagnosing PE, pulmonary angiography is no longer routinely used. Considering the invasive nature of the procedure, the potential
for higher radiation exposure, and the signicantly higher
cost, there is little evidence to support the use of pulmonary angiography as a rst-line study.
59
Based on the PIOPED patient population, an analysis of
pulmonary angiography demonstrated 98% interobserver
agreement for PE in the main or lobar pulmonary arteries and 90% interobserver agreement for PE limited to the
segmental or subsegmental pulmonary arteries. When PE
limited to the subsegmental arteries was studied, there was
only 66% interobserver agreement.
In earlier studies, pulmonary angiography demonstrated considerably higher sensitivity than s-CT (67%).
71
72
Even with considerable improvement in multidetector CT
technology, pulmonary angiography continues to show
higher sensitivity, although the gap is smaller and may be
of limited clinical signicance.
nary angiogram, 0.6% of the patients followed were noted
to have a PE.
74
73
After a negative pulmo-
The complications associated with pulmonary angiography are limited but not insignicant. In a study based
on the PIOPED patients, complications were noted to be
death in 0.5%, major nonfatal complications in 1%, and
less signicant events in 5%.
experienced renal dysfunction after the study.
74
Atotal of 1% of patients
74
18.2.6 D-dimer
The utility of D-dimer assays in the workup of PE and
DVT is quite similar. Both conditions are a part of the same
disease spectrum, and it stands to reason that the ndings
would show a high degree of congruity.
A systematic review of prospective studies on the diagnostic role of D-dimer concluded that the ELISA and quantitative rapid ELISA had the highest sensitivities (96%)
and negative likelihood ratios (0.13) among the various
75
assays.
specicity were noted in other studies as well.
Similar results of high sensitivity but moderate
76–78
In one
study, it was also suggested that D-dimer levels were of
greater benet in the outpatient setting, since conditions
that could lead to false-positive results (e.g., inammation,
trauma, and surgery) were more often seen in the inpatient
75
setting.
patients, there is as yet no clear consensus.
As for the diagnostic role of D-dimer in pregnant
76
With high sensitivity and only moderate specicity, the
D-dimer assay is limited in its ability to accurately rule in PE.
However, the combination of a low- to moderate-probability
score using a clinical assessment scale and a normal D-dimer
assay result can effectively rule out the presence of PE.
60,63,77
Unfortunately, negative D-dimer assay results in patients
with high-probability clinical assessments are still associated
with PE rates of more than 15% and should not be relied
upon. Further testing is indicated in the high-risk group.
77
18.2.7 Spiral CT
s-CT has emerged as one of the predominant studies
for the diagnosis of PE. Not only is the study less inva-
sive than pulmonary angiography, it also has the ability
to depict other conditions that may be confused with PE.
Pneumonia, pneumothorax, pneumomediastinum, pleural/
pericardial effusion, aortic dissections, and various other
conditions can mimic the signs and symptoms of PE and
have been noted in 11%–70% of CT examinations performed for suspected PE.
65
In the 1990s, studies comparing s-CT to VP scans and
angiography were based on single-detector CT scanners.
Despite technological limitations, s-CT was noted to be
useful in the diagnosis of PE, especially in the scenario of
intermediate-probability VP scans. In one prospective study
comparing scintigraphy to s-CT with pulmonary angiography as the gold standard, s-CT was in concordance with
angiography 80% of the time in patients noted to have
intermediate-probability VP scans.
patients with intermediate-probability VP scans demonstrated a PE rate of 24.4% using s-CT.
79
A separate study of
80
The superiority
of s-CT over VP scanning is supported by other studies as
well, but the reported sensitivity of s-CT has ranged widely,
from 53% to 100%.
65,72,81,82
With the single-detector CT scanners, subsegmental
and peripheral pulmonary arteries were poorly visualized,
and sensitivities for PE in these locations were especially
83
False-negative rates of single-detector CT scanning
low.
were as high as 30% when used alone.
84,85
The current generation of multiple-detector CT
(MDCT) scanners is faster and able to visualize smaller
pulmonary arteries.
86
As a result, higher sensitivities have
been reported that rival even pulmonary angiography.
For subsegmental pulmonary arteries evaluated with single-detector, 4-MDCT, and 16-MDCT scanners, the arteries were well visualized in 36%, 75%, and 88% of the
scans, respectively.
65
In recent years, the impetus has been
to perform synchronous indirect CT venography and CT
pulmonary angiography scans. By doing so, the presence of
both PE and DVT can be evaluated with higher sensitivity
and similar specicity.
59,65,87
These analyses, however, are
biased regarding DVT sensitivity and/or specicity, as the
samples are derived from PE patient groups, which have a
higher incidence of DVT.
18.2.8 MRI/magnetic resonance
angiography
The use of MRI/magnetic resonance angiography (MRA)
for the diagnosis of PE has received greater attention in
recent years. Even with this increased interest, however,
most diagnostic algorithms and recommendations, including PIOPED II, only mention MRI briey.
The sensitivity of MRA when compared to conventional
angiography ranges from 77% to 100%, depending on the
88,89
study.
imaging, there is a subsequent increase in sensitivity rivaling
that of 16-MDCT angiography.
With the addition of magnetic resonance perfusion
90
The current role for MRI/
MRA is as a backup when conventional diagnostic methods
are unavailable or contraindicated due to dye allergy, renal
insufciency, or concerns about radiation exposure.
MRI may also prove to be valuable in the follow-up of acute
PE in order to determine thrombus age.
Notably, recent studies have questioned the tradi-
tional thinking that gadolinium was less nephrotoxic than
59
91
59,88,89
18
73
200 Chapter 18 Diagnostic algorithms for acute deep venous thrombosis and pulmonary embolism
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iodinated contrast. In fact, at angiographic concentrations,
gadolinium has demonstrated equal or greater renal cell
toxicity than iodinated contrast.
32
There is also mounting
evidence that gadolinium administration may play a signicant role in the development of nephrogenic systemic
brosis.
33–35
18.2.9 Other studies
Other modalities have been studied with the intention of
using them for the diagnosis of PE, with varying levels of
success. Although electrocardiogram (ECG) changes may
be present, they are neither sensitive nor specic for PE.
The changes may, however, indicate a way of stratifying
risk, since patients with acute major PE and ECG changes
have worse outcomes than those without the changes.
Likewise, although arterial blood gas changes may be present, they are nonspecic and therefore of limited diagnostic
utility in the workup of PE.
94
Lastly, although chest radiographs are routinely ordered in those experiencing respiratory distress, the results are most often normal, even in
the presence of PE. Chest radiographs may be useful for
determining which patients should undergo s-CT versus
VP scintigraphy, since abnormal chest radiographs increase
the likelihood of indeterminate-probability VP scans.
Once a PE has been conrmed, algorithms now exist
to help risk-stratify patients into treatment groups and/or
testing groups for further evaluation. The process of patient
risk stratication helps identify patients who will do well
with standard therapy and who are likely to need more
aggressive treatment. This also helps determine resource
utilization. Some patients with small, incidental PE and
some segmental PE are now being treated as outpatients,
while other patients may require immediate interventional
therapy, either operative or lytic. Two different scoring systems have been used to predict the severity of PE. These
include the Pulmonary Embolism Severity Index (PESI)
score and the Geneva score (Table18.4).
In validation studies, a PESI score of less than 66 predicts a 30-day mortality rate of less than 3%.
96,97
98
have recently been completed of large multinational randomized trials comparing outcomes and costs for inpatient
management versus immediate discharge from ambulatory
centers when patients had a PE diagnosed and a PESI score
of less than 66 (Figures18.8–18.11).
98,99
The use of ECG, biomarkers, echocardiography, and CT
pulmonary angiogram ndings can be combined to predict
mortality in those with and without right ventricular dysfunction. For patients with right ventricular dysfunction,
mortality is 15%; for those without, mortality is 5%. If
there is elevated troponin, the mortality rate is greater than
43%, while those without have less than 15% mortality.
In those with an elevated brain natriuretic peptide (BNP),
the mortality risk is 47%, but less than 13% in those who
lack elevated BNP. For those with an elevated N-terminal
prohormone of BNP (proBNP), mortality is 32%; if it is
not elevated, mortality is less than 5%.
98
Experts can then bundle these stratication data in
order to categorize patients into risk categories and thus
determine different treatment and monitoring needs
(Table18.5). Patients at low risk for PE may require heparin anticoagulation with either low-molecular-weight or
92
93
95
Studies
TABLE 18.4 Two scoring systems to predict the severity
of pulmonary embolism
PESI score
Age, per year Number of years of life
Male gender 10
Cancer 30
Heart failure 10
Chronic lung disease 10
Pulse >110 beats/minute 20
Systolic blood pressure <100 mmHg 30
Respiratory rate >29 breaths/minute 20
Temperature <36°C 20
Altered mental status 60
SaO
Low-risk score <66
High-risk score >125
Geneva score
Cancer 2
Heart failure 1
Prior deep venous thrombosis 1
Systolic blood pressure <100 mmHg 2
PaO
Concomitant deep venous thrombosis 1
Low-risk score <3
High-risk score >2
Source: From Kline JA, Miller DW. J Natl Compr Canc Netw 2011;9(7):800–
10. With permission.
Abbreviations: PaO2: arterial partial pressure of oxygen; PESI: Pulmonary
Embolism Severity Index; SaO2: percentage of oxygen saturation of arterial
blood.
18.8 Right ventricular shift into the left ventricle.
96
<90% 20
2
97
<8 kPa 1
2
Points assigned
18.2 Pulmonary embolism 201
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18
18.9 Bowing of septum into the left ventricle.
18.10 Proximal pulmonary emboli.
unfractionated heparin. Patients at low risk for PE also
can be admitted to an unmonitored bed, and some of these
patients may be discharged directly to home.
Patients with moderate-risk PE should be hospitalized with telemetry monitoring and initial heparinization. Any patient with degradation or development of
new or worsening signs should undergo repeat biomarker testing and echocardiography. The risk should
be re-evaluated.
100–109
18.11 Central saddle embolus.
Patients with more severe and moderate PE or submassive
PE may require more aggressive care and monitoring, with
consideration of brinolytic therapy (Figures 18.12, 13).
The treatment of submassive embolism remains one of the
most controversial subjects and is currently the subject of
much ongoing research.
High-risk patients may also be reported as severe, and
major PE may occur in association with hypotension and
may require heparin anticoagulation, intensive care unit
monitoring, and treatment escalation.
The most common relative contraindications for brinolytic therapy include age over 80years, advanced directives, a “do not resuscitate” order, trauma associated with
syncope or seizure-like presentation, anemia or thrombocytopenia, current menstruation, recent childbirth, a
remote or vague history of stroke, gastrointestinal bleeding, and metastatic carcinoma.
110
18.2.10 Algorithm use for DVT and PE
The use of algorithms seeks to separate patients into
risk groups for testing and evaluation while not missing
any signicant pathologies. The algorithms only apply
to symptomatic outpatients, using exclusion criteria to
increase sensitivity and specicity. They have not been validated for inpatients or asymptomatic patients. Algorithms
perform differently in different populations and when used
by different care providers. Astandardized treatment management plan is also dened through the algorithms. These
may be useful with inexperienced staff and may decrease
practice variation and provide some control over risk management. Algorithms do not include consideration of diagnostic uncertainty and patient anxiety while waiting for a
denitive diagnosis. Clinician and patient acceptance are
required to use an algorithm, and the algorithm should utilize tests that are widely available.
202 Chapter 18 Diagnostic algorithms for acute deep venous thrombosis and pulmonary embolism
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TABLE 18.5 Criteria for categorizing patients with acute pulmonary embolism and associated treatment options
Category Definition Recommended treatment options
Low risk Systolic blood pressure >90 mmHg at all times and all of the
following:
• Shock index ≥1
• SaO2 almost always >94%
• Normal electrocardiogram (or Daniel score <3)
• Normal troponin and BNP or proBNP
• PESI score <66
Moderate risk Systolic blood pressure >90 mmHg at all times and any one of the
following:
• Shock index >1 at any time
• SaO
persistently <94%
2
• Electrocardiogram showing any signs of pulmonary hypertension
(tachycardia, S1Q3T3, or incomplete RBBB)
• Elevated troponin or BNP or proBNP
• PESI score >65
• Echocardiography with any degree of right ventricular hypokinesis
More severe
(submassive)
moderate risk
Appearance of at least moderate distress and:
• Shock index >1 and severe right ventricular hypokinesis on
echocardiography
• Worsening electrocardiogram, such as S1Q3T3 and a new
incomplete RBBB, or progression of incomplete to complete
RBBB, or development of T-wave inversion in V1–V3
High risk
(major)
Any systolic blood pressure <90 mmHg or <20 mmHg below documented baseline and appearance of distress
Any persistent systolic blood pressure <90 mmHg regardless of
appearance
• Begin low-molecular-weight heparin
• Optional admission to unmonitored regular bed
• Consider outpatient treatment if adequate
compliance and follow-up can be assured
• Begin heparin treatment
• Fibrinolytics in the minority of cases
• Admission to a telemetry bed
• Begin heparin treatment
• Fibrinolytic treatment in most patients without
contraindications in the emergency department
• Admission to a step-down or intensive care
unit
• Begin heparin treatment
• Fibrinolytic treatment in the emergency department in all patients without contraindications
• Admission to intensive care unit
Abbreviations: BNP: brain natriuretic peptide; PESI: Pulmonary Embolism Severity Index; proBNP: prohormone of brain natriuretic peptide; RBBB: right
bundle branch block; SaO2: percentage of oxygen saturation of arterial blood.
Hemodynamic
Clinical exam
Biomarkers
Echocardiography
or CT
Risk stratification
Treatment
Location
Normotensive
PESI < 85 PESI ≥ 85
BNP – and
tropo –
Low
LMWH or Fx LMWH or Fx
New anticoagulants ?
Outpatient early
discharged
Intermediate
less-severe
Hospitalization IC
BNP + or
tropo +
No RV
dilatationRVdilatation
Intermediate
more-severe
UFH
Hypotension
shock
High
Thrombolysis
CU
18.12 Algorithm management in risk stratication and treatment strategy for patients with acute pulmonary embolism. BNP: brain
natriuretic peptide; Fx: fondaparinux; ICU: intensive care unit; LMWH: low-molecular-weight heparin; PESI: Pulmonary Embolism
Severity Index; RV: right ventricle; tropo: troponin; UFH: unfractionated heparin.
Source: (From Penaloza A, Roy PM, Kline J. Curr Opin Crit Care 2012;18:318–25.)
18.2 Pulmonary embolism 203
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18.2.11 Thrombus in transit
Free-oating right heart thrombi are a rare phenomenon
seen almost exclusively in patients with suspected or proven
PE. Most commonly they are diagnosed by transthoracic
echocardiography but may occasionally be seen on CT pulmonary angiography (CTPA). This represents an extreme
therapeutic emergency, as any delay in treatment may be
lethal. Twenty-one percent will die in the rst day after
admission. Overall mortality is 44.7%. Immobile thrombi
are not included in this, as they represent in situ thrombosis
commonly seen with COVID or in the left atrium. Echocardiogram ndings demonstrate signs of cor pulmonale,right
ventricular overload (91.7%), paradoxical interventricular
septal motion (75%), and pulmonary hypertension (86%).
The thrombus is most typically wormlike in nature. In
patients with a patent foramen ovale, thrombi may extend
from the left atrium. In-hospital mortality rates are signicantly linked to the occurrence of cardiac arrest. Clots in
transit have been dened as a right heart thrombus not
attached to any intracardiac structure Figures18.14, 15.
There are type Aand type B thrombi. Type Aare wormlike
and are considered free-oating “in transit.” They are very
mobile and represent peripherally formed venous clots that
lodged temporarily into the right heart. Type B are similar
to the left heart thrombi, less mobile, and attached to the
right atrium or ventricular wall with a broad-based attachment, indicating that type B clots develop in the right heart
itself. Reported incidence of in-transit thrombi is less than
4%. The presence of a thrombus in transit represents a true
emergent clinical entity. Aclot in transit in the setting of
massive/submassive PE is a life-threatening condition that
requires multidisciplinary team involvement for timely
diagnosis and urgent treatment.
111,112
18
18.13 Multiple PEs.
18.2.12 DVT/PE in children
VTE during childhood is considerably lower than in adults;
however, it is increasingly recognized in the pediatric
18.14 CT PE with additional ndings of septal straightening,
clot within the ventricle, and intact papillary muscles.
18.15 Intraventricular thrombi in transit.
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