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200 Computed tomography and magnetic resonance imaging in venous disease
https://t.me/med1917
Table 16.1 Advantages and disadvantages of computed
tomography and magnetic resonance imaging for the
evaluation of venous disease
Advantages Disadvantages
Computed
tomography
Magnetic
resonance
imaging
Speed Iodinated contrast
Superior spatial
resolution
Calcifications
No radiation
exposure
No iodinated
contrast
Multiple
acquisitions
possible
Superior contrast
resolution
Radiation
Contraindications
Pacemaker
Aneurysm clips
Claustrophobia
1 mm. Standard acquisition times for 3D SPGR MR venography sequences are generally between 10 and 20 seconds,
which is occasionally problematic for patients who are short
of breath. e in-plane spatial resolution for typical MR
venography acquisitions is ≤1 mm; however, slice thickness
is generally in the range of 2–4 mm—signicantly lower
than CT, but generally adequate for most applications. CT is
also preferable in patients with claustrophobia, pacemakers,
or other contraindications to MR.
On the other hand, MR is a much more exible technique, with numerous non-contrast and CE methods relying on dierent contrast mechanisms, so that more choices
are available in dicult cases. In general, contrast-to-noise
ratios of venous blood are signicantly higher with MRI,
although SNRs are occasionally lower. MR venography is
preferred in patients with allergies to iodinated contrast
or renal insuciency. MR venography is also the test of
choice in patients without venous access, since many noncontrast techniques are available with MRI and not with
CT. Radiation dose is also a consideration, particularly in
pediatric or pregnant patients or other radiation-sensitive
populations (Table 16.1).
16.3.5 Future prospects
e recognition that gadolinium-based contrast agents
could cause nephrogenic systemic brosis (NSF) when
administered to patients with severe renal insuciency
has led to the development of several robust non-contrast
MRA techniques, the most common of which employ 3D
SSFP or 3D FSE pulse sequences.
31,46,47
ese methods have
Guidelines 2.6.0 of the American Venous Forum on computed tomography and magnetic resonance imaging in venous
disease
Grade of evidence
(A:high quality;
B:moderate
quality; C: low or
very low quality)
No. Guideline
2.6.1 Computed tomography with intravenous contrast is recommended for
the evaluation of obstruction of large veins in the chest, abdomen,
and pelvis. Computed tomography accurately depicts the underlying
pathology and confirms extrinsic compression, tumor invasion,
traumatic disruption, anatomic variations, extent of thrombus, and
position of a caval filter.
2.6.2 Computed tomography with intravenous contrast is recommended to
diagnose pulmonary embolism. Sensitivity and specificity approaches
100% for central emboli, whereas for small, sub-segmental pulmonary
emboli, sensitivity and specificity are 83% and 96%, respectively.
2.6.3 Magnetic resonance venography is recommended for the diagnosis of
acute iliofemoral and caval deep vein thrombosis. A sensitivity of
100% and specificity of 96% was reported. The study is also
recommended for the diagnosis of portal, splenic, or mesenteric
venous thrombosis.
2.6.4 Magnetic resonance imaging and magnetic resonance venography are
highly accurate for imaging inferior vena cava thrombus associated
with renal, adrenal, retroperitoneal, primary caval, or metastatic
malignancies. Magnetic resonance venography reveals the presence
or absence of bland thrombus or tumor thrombus in the renal veins
and inferior vena cava.
Grade of
recommendation
(1:strong;
2:weak)
1 B
1 A
1 A
1 A
References 201
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robust background suppression and enable 3D reconstructions that are very similar in appearance to those obtained
from 3D CE MRA and have been shown to be as accurate
or nearly as accurate as standard 3D CE MRA, in a variety of situations, such as assessment of renal artery stenosis.
e same techniques can be applied to venography, and it is
likely that similar success will be achieved in non-contrast
venous imaging.
16.4 SUMMARY
CT and MR are both eective tools for answering a large
number of clinical questions regarding the venous system.
Each technique has unique advantages and disadvantages,
as outlined above. Advances in each technology will continue to provide optimal imaging evaluation for a wide
variety of venous disorders.
REFERENCES
●
= Key primary paper
★
= Major review article
★
1. McCollough CH, Bruesewitz MR, and Kofler JM Jr.
CT dose reduction and dose management tools:
Overview of available options. Radiographics
2006;26:503–12.
2. Eren S, Karaman A, and Okur A. The superior
vena cava syndrome caused by malignant disease.
Imaging with multi-detector row CT. Eur J Radiol
2006;59:93–103.
3. Cihangiroglu M, Lin BH, and Dachman AH. Collateral
pathways in superior vena caval obstruction as seen
on CT. J Comput Assist Tomogr 2001;25:1–8.
4. Siegel MJ. Multiplanar and three-dimensional multidetector row CT of thoracic vessels and airways in
the pediatric population. Radiology 2003;229:641–50.
5. Lawler LP and Fishman EK. Multi-detector row CT
of thoracic disease with emphasis on 3D volume
rendering and CT angiography. Radiographics
2001;21:1257–73.
★
6. Zhang L, Yang G, Shen W, and Qi J. Spectrum of
inferior vena cava: MDCT findings. Abdom Imaging
2007;32:495–503.
7. Minniti S, Visentini S, and Procacci C. Congenital
anomalies of the venae cavae: Embryological origin,
imaging features and report of three new variants.
EurRadiol 2002;12:2040–55.
8. Bass JE, Redwine MD, Kramer LA etal. Spectrum
of congenital anomalies of the inferior vena cava:
Cross-sectional imaging findings. Radiographics
2000;20:649–52.
9. Trigaux JP, Vandroogenbroek S, De wispelaere JF
etal. Congenital anomalies of the inferior vena cava
and left renal vein: Evaluation with spiral CT. J Vasc
Interv Radiol 1998;9:339– 45.
10. Alfuhaid TR, Khalili K, Kirpalani A etal. Neoplasms
of the inferior vena cava-pictorial essay. Can Assoc
Radiol J 2005;56:140–7.
11. Ameeri S, Butany J, Collins MJ etal.
Leiomyosarcoma of the inferior vena cava.
Cardiovasc Pathol 2006;15:171–3.
12. Remy-Jardin M, Remy J, Deschildre F etal. Diagnosis
of pulmonary embolism with spiral CT: Comparison
with pulmonary angiography and scintigraphy.
Radiology 1996;200:699–706.
●
13. Remy-Jardin M, Remy J, Wattinne L, and Giraud F.
Central pulmonary thromboembolism: Diagnosiswith
spiral volumetric CT with the single- breath-hold technique—Comparison with pulmonary angiography.
Radiology 1992;185:381–7.
●
14. Stein PD, Fowler SE, Goodman LR etal.
Multidetector computed tomography for
acute pulmonary embolism. N Engl J Med
2006;354:2317–27.
●
15. Stein PD, Woodard PK, Weg JG etal. diagnostic pathways in acute pulmonary embolism:
Recommendations of the PIOPED II Investigators.
Radiology 20 07;242:15 –21.
16. Oguzkurt L, Tercan F, Pourbagher MA etal.
Computed tomography findings in 10 cases of
iliac vein compression (May–Thurner) syndrome.
EurJRadiol 2005;55:421–5.
17. Lamont JP, Pearl GJ, Patetsios P etal. Prospective
evaluation of endoluminal venous stents in the
treatment of May–Thurner syndrome. Ann Vasc Surg
2002;16:61–4.
18. O’Sullivan GJ, Semba CP, Bittner CA etal.
Endovascular management of iliac vein compression
syndrome. J Vasc Interv Radiol 2000;11:823–36.
●
19. Carpenter JP, Holland GA, Baum RA etal. Magnetic
resonance venography for detection of deep venous
thrombosis: Comparison with contrast venography
and duplex Doppler ultrasonography. J Vasc Surg
1993;18:233– 8.
●
20. Evans AJ, Sostman HD, Knelson MH etal. Detection
of deep venous thrombosis: Prospective comparison of MR imaging with contrast venography.
AJRAmJRoentgenol 1993;161:131–9.
★
21. Vogt FM, Herborn CU, and Goyen M. MR venography. Magn Reson Imaging Clin N Am 20 0 5;13:113 – 29.
22. Cantwell CP, Cradock A, Bruzzi J etal. MR venography with true fast imaging with steady-state precession for suspected lower-limb deep vein thrombosis.
J Vasc Interv Radiol 20 0 6;17:1763–9.
23. Lee CU and Glockner JF. Vascular staging of renal
and adrenal malignancies with a noncontrast
enhanced steady state free precession technique.
JMagn Reson Imaging 2011;33:1406 –13.
●
24. Choyke PL, Walther MCM, Wagner JR etal. Renal
cancer: Preoperative evaluation with dual-phase,
three-dimensional MR angiography. Radiology
1997;205:767–71.
202 Computed tomography and magnetic resonance imaging in venous disease
https://t.me/med1917
25. Shinde TS, Lee VS, Rofsky NM etal. Threedimensional gadolinium-enhanced MR venographic evaluation of patency of central veins
in the thorax: Initial experience. Radiology
1999;213:555–60.
26. Lin J, Zhou KR, Chen ZW etal. Vena cava 3D contrast-enhanced MR venography: A pictorial review.
Cardiovasc Intervent Radiol 2005;28:795–805.
27. Huang SY, Kim CY, Miller MJ etal. Abdominopelvic
and lower extremity deep venous thrombosis:
Evaluation with contrast-enhanced MR venography
with a blood-pool agent. AJR Am J Roentgenol
2013;201:208–14.
28. Daftari Besheli L, Aran S, Shaqdan K, Kay J, and
Abujudeh H. Current status of nephrogenic systemic
fibrosis. Clin Radiol 2014;69:661–8.
29. Ruehm SG, Zimny K, and Debatin JF. Direct contrast-enhanced 3D MR venography. Eur Radiol
20 01;11:102–12.
30. Tanju S, Sancak T, Dusunceli E etal. Direct contrastenhanced 3D MR venography evaluation of upper
extremity deep venous system. Diagn Interv Radiol
2006;12:74 – 9.
31. Kim CY, Bashir MR, Heye T etal. Respiratory-gated
noncontrast SPACE MR angiography sequence
at 3T for evaluation of the central veins of the
chest: A feasibility study. J Magn Reson Imaging
2015;41:67–73.
32. Gao K, Jiang H, Zhai RY etal. Threedimensional gadolinium-enhanced MR venography to evaluate central venous steno-occlusive
disease in hemodialysis patients. Clin Radiol
2012;67:560–3.
33. Schonberger M, Usman A, Galizia M etal. Timeresolved MR venography of the pulmonary veins
precatheter-based ablation for atrial fibrillation.
JMagn Reson Imaging 2013;37:127–37.
34. Malcome-Lawes LC, Juli C, Karim R etal. Automated
analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and
clinical outcomes: A 2-center study. Heart Rhythm
2013;10:1184–91.
35. Valsangiacomo ER, Levasseur S, McCrindle BW etal.
Contrast-enhanced MR angiography of pulmonary
venous abnormalities in children. Pediatr Radiol
2003;33:92–8.
36. Laissy JP, Menegazzo D, Debray MP etal.
Renal carcinoma: Diagnosis of venous invasion
with Gd-enhanced MR venography. Eur Radiol
20 00;10:1138 – 43 .
37. Hallscheidt PJ, Bock M, Riedasch G etal. Diagnostic
accuracy of staging renal cell carcinoma using
multidetector-row computed tomography and magnetic resonance imaging. J Comput Assist Tomogr
2004;28:333–9.
38. Hallscheidt PJ, Fink C, Haferkamp A etal.
Preoperative staging of renal cell carcinoma with
inferior vena cava thrombus using multidetector CT and MRI: Prospective study with histopathological correlation. J Comput Assist Tomogr
2005;29:64–8.
39. Hussain SM, Kock MCJM, Ifzermans JNM etal. MR
imaging: A one-stop shop modality for preoperative evaluation of potential living kidney donors.
Radiographics 2003;23:505–20.
40. Liu H, Cao H, and Wu ZY. Magnetic resonance
angiography in the management of patients with
portal hypertension. Hepatobiliary Pancreat Dis Int
2005;4:239–43.
41. Fraser DGW, Moody AR, Davidson IR etal. Deep
venous thrombosis: Diagnosis using venous enhanced
subtracted peak arterial MR venography versus conventional venography. Radiology 2003;226:812–20.
42. Ruehm SG, Wiesner W, and Debatin JF. Pelvic and
lowerextremity veins: Contrast-enhanced threedimensional MR venography with a dedicated vascular coil—Initial experience. Radiology 2000;215:421–7.
43. Kluge A, Mueller C, Strunk J etal. Experience in 207
combined MRI examinations for acute pulmonary
embolism and deep vein thrombosis. AJR Am J
Roentgenol 2006;186:1686–96.
44. Dick EA, Burnett C, Anstee A etal. Time-resolved
imaging of contrast kinetics three-dimensional
magnetic resonance venography in patients with pelvic
congestion syndrome. Br J Radiol 2010;83:882–7.
45. Lim RP, Bruno M, Rosenkrantz AB etal. Comparison
of blood pool and extracellular gadolinium chelatefor functional MR evaluation of vascular thoracic outlet syndrome. Eur J Radiol 2014;83:1209–15.
46. Furuta A, Isoda H, Yamashita R etal. Non-contrastenhanced MR portography with balanced steadystate free-precession sequence and time-spatial
labeling inversion pulses: Comparison of imaging
with flow-in and flow-out methods. J Magn Reson
Imaging 20 14;40:583 –7.
47. Shimada K, Isoda H, Okada T etal. Unenhanced
MR portography with a half-Fourier fast spinecho sequence and time-space labeling inversion
pulses: Preliminary results. AJR Am J Roentgenol
20 09;193:106–12.
PART 3
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Management of Acute Thrombosis
17 The clinical presentation and natural history of acute deep venous thrombosis 205
Mark H. Meissner
18 Diagnostic algorithms for acute deep venous thrombosis and pulmonary embolism 221
Joann Lohr
19 Medical treatment of acute deep venous thrombosis and pulmonary embolism 239
Andrea T. Obi and Thomas W. Wakefield
20 Catheter-directed thrombolysis, mechanical thrombectomy, and surgery for the treatment
ofacuteiliofemoraldeep venous thrombosis 251
Arthur Delos Reyes and Anthony J. Comerota
21 Endovascular and surgical management of acute pulmonary embolism 265
Erin S. DeMartino and Randall R. DeMartino
22 Treatment algorithms for acute venous thromboembolism: Current guidelines 277
Andrea T. Obi and Thomas W. Wakefield
23 Current recommendations for the prevention of deep venous thrombosis 289
Robert D. McBane and John A. Heit
24 Axillo-subclavian venous thrombosis in the setting of thoracic outlet syndrome 309
Aurelia T. Calero and Karl A. Illig
25 Acute central venous thrombosis in the setting of central lines, pacemaker wires, and dialysis catheters 317
Syed Ali Rizvi, Anil Hingorani, and Enrico Ascher
26 Indications, techniques, and results of inferior vena cava filters 325
Scott T. Robinson, Venkataramu N. Krishnamurthy, and John E. Rectenwald
27 Superficial thrombophlebitis 343
Benjamin Jacobs and Dawn M. Coleman
28 Mesenteric vein thrombosis 349
Waldemar E. Wysokinski and Robert D. McBane
https://t.me/med1917
17
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The clinical presentation and natural history of
acute deep venous thrombosis
MARK H. MEISSNER
17.1 Introduction 205
17.2 Clinical presentation of acuteDVT 205
17.3 Complications of acute DVT 206
17.4 The natural history of acuteDVT 207
17.1 INTRODUCTION
e spectrum of venous thromboembolism (VTE) includes
both deep venous thrombosis (DVT) and pulmonary embolism (PE). Among 2119 patients enrolled in a prospective,
multicenter registry, 72.7% had DVT, 9.7% had PE, and
17.5% had both DVT and PE.1 First episodes of clinically
recognized DVT occur with an age-adjusted incidence of
50.4 per 100,000 person-years.2 However, many episodes are
asymptomatic and the symptoms of acute DVT, including
edema, pain, and erythema,1 are non-specic. e formation of thrombi within the venous system depends in large
measure on imbalances within the coagulation and brinolytic systems, and similar interactions continue to be important throughout the subsequent evolution of these thrombi.
Over time, the processes of recanalization and organization compete with thrombus extension and re-thrombosis.
Recurrent thrombosis and the post-thrombotic syndrome
dominate the late natural history of acute DVT. e treatment of DVT is aimed at preventing its complications—PE,
recurrent DVT, the post-thrombotic syndrome, and death.
ese complications are closely related to the natural history of DVT, an understanding of which is required for
determining optimal management.
17.2 CLINICAL PRESENTATION OF
ACUTEDVT
e clinical presentation of an acute DVT varies with the
anatomic distribution, extent, and degree of occlusion of the
thrombus. Symptoms may accordingly range from being
absent to massive swelling and cyanosis with impending
17.5 The natural history of DVT and the
post-thrombotic syndrome 211
17.6 Clinical applications of natural history studies 213
References 215
venous gangrene (phlegmasia cerulea dolens). Although
DVT has historically been characterized as involving the
proximal or distal veins, there are in fact three anatomic
patterns—isolated calf vein (distal), femoropopliteal, and
iliofemoral thrombosis—that have somewhat dierent
natural histories. e Guidelines of the Society for Vascular
Surgery (SVS) and the American Venous Forum (AVF)
accordingly recommend the use of precise anatomic terminology to characterize the most proximal extent of venous
thrombosis as involving the iliofemoral veins, with or without extension to the inferior vena cava, the femoropopliteal
veins, or isolated to the distal calf veins.
Symptoms do tend to be more severe as thrombosis
extends more proximally. When present, signs and symptoms of acute DVT may include pain, edema, erythema,
tenderness, fever, prominent supercial veins, pain with
passive dorsiexion of the foot (Homan’s sign), and peripheral cyanosis. Although potentially associated with concurrent DVT, a palpable cord is more suggestive of supercial
venous thrombosis. However, up to 50% of patients with
an acute DVT may lack specic signs and symptoms.
Post-operative patients are, in particular, more likely to
have small, asymptomatic, distal, non-occlusive thrombi.
Phlegmasia cerulea dolens, characterized by the triad of
massive swelling, cyanosis, and pain,6 is the most severe
form of acute DVT and results from near-complete thrombosis of an extremity’s venous outow. In advanced cases,
it is marked by severe venous hypertension with collateral
and microvascular thrombosis, leading to venous gangrene.
Venous gangrene has been particularly associated with warfarin-mediated protein C depletion in patients with cancer
or heparin-induced thrombocytopenia.
3
4,5
7,8
205
206 The clinical presentation and natural history of acute deep venous thrombosis
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e diagnosis of acute DVT based upon clinical signs
and symptoms alone is notoriously inaccurate. e signs
and symptoms are non-specic and may be associated with
other lower extremity disorders, including lymphedema,
the post-thrombotic syndrome, supercial venous thrombosis, cellulitis, musculoskeletal trauma, and Baker’s cysts.
Among patients referred to the vascular laboratory for
exclusion of DVT, only 12%–31% will have a positive ultrasound st udy.
extremity ndings, 3.3% of which will be signicant.
9–11
However, 12.8% will have incidental lower
12
e most common presenting symptoms have a wide
range of reported sensitivities and specicities: calf pain,
sensitivity 75%–91% and specicity 3%–87%; and calf swelling, sensitivity 35%–97% and specicity 8%–88%.
13−18
None
of the signs or symptoms are suciently sensitive or specic, either alone or in combination, to accurately diagnose
or exclude thrombosis.19 For example, although Markel
etal.10 found a history of swelling in 83% of patients with
a DVT, it was also present in 63% of those with a clinical
suspicion but no documented DVT. Limb pain was similarly present in 51% and 41% of patients with and without
DVT, respectively. e overall sensitivity and specicity of
the clinical examination have ranged from 60% to 96% and
from 20% to 72%, respectively.
20
e accuracy of the clinical evaluation also diers
between inpatients and outpatients. Inpatients are more
likely to have undergone surgery or to be critically ill,
while outpatients are less likely to have had recent surgery,
trauma, or a prior DVT.9 Additionally, the incidence of DVT
is lower among outpatients, while specic leg symptoms are
more common. e absence of certain risk factors, signs, or
symptoms may thus have a higher negative predictive value
in outpatients.
11
As the clinical presentation of acute DVT is non-specic,
the presence or absence of associated thrombotic risk factors may alter diagnostic suspicion. For example, in outpatients without cancer, a duration of symptoms of greater
than 7 days and a dierential thigh circumference of <3 cm
has a negative predictive value of 95%.11 Unfortunately, the
positive predictive value is only 28.6%. Similarly, a dierence in calf circumference of <2 cm demonstrated a negative predictive value of 85% among outpatients and 93%
among inpatients.
9
However, when combined with the
absence of risk factors, the negative predictive value of the
absence of swelling increased to 97% in outpatients and 92%
in inpatients. Despite these observations, withholding treatment based only on empirical clinical observations poses
an unacceptable thromboembolic risk of up to 2%–4% in
secondary referral outpatients, 8% in inpatients, and 12%
in primary care patients.
9,11, 21
Further diagnostic testing
is therefore usually necessary, both to ensure appropriate
treatment of those with conrmed DVT and to prevent the
complications of inappropriate anticoagulation in those
with other disorders.
Clinical assessment does, however, have a role in determining pre-test probability in algorithms incorporating further diagnostic modalities such as venous duplex
ultrasonography and D-dimer measurements.22 e probability model developed and validated by Wells et al.23
has been used most widely. e model eectively straties
patients into low, moderate, and high pre-test probability
groups based on the presence of cancer; lower extremity
immobilization by paralysis or plaster dressings; recent surgery or bed rest longer than 3 days; thigh and calf swelling; tenderness along the course of the deep veins; a >3-cm
increase in calf circumference; pitting edema; collateral
supercial vein; and the possibility of an alternative diagnosis. A valid alternative diagnosis, most oen cellulitis
or musculoskeletal disorders, is present in 56% of those
without DVT, in comparison to only 17% of those with
conrmed DVT.
24,25
Unfortunately, although such models
are useful in guiding further diagnostic tests, the 3% prevalence of DVT in low-probability patients precludes diagnosis based on clinical strategies alone.23 Fortunately, D-dimer
has an excellent negative predictive value in low-probability
outpatients, and algorithms combining clinical pre-test
probability assessment, D-dimer measurement, and venous
duplex ultrasound have been developed and validated.
22
Delayed diagnosis of DVT is not uncommon. Among
2047 patients with symptomatic DVT, a diagnosis was
established within 5 days of the onset of symptoms in
only 47.1%, while it was delayed beyond 10 days in 22.6%.1
Much of this time can be attributed to delays in presentation, with patients on average presenting for medical
attention 4.4 days aer the onset of symptoms.26 Although
diagnostic delays are oen shorter,26 many of these can be
attributed to inadequate appreciation of a patient’s underlying risk factors.
1
17.3 COMPLICATIONS OF ACUTE DVT
17.3.1 Pulmonary embolism
e potentially life-threatening consequences of PE make
it the most important short-term complication of acute
DVT. Symptomatic PE accompanies approximately 10% of
DVTs.27 Recent reviews report an incidence of 29–78 per
100,000 for isolated PE.
tially increased since 2001, likely related to the increased
availability of computed tomography and magnetic resonance pulmonary angiography.28 Despite this observation,
the age-adjusted PE mortality rate in France declined by 3%
per year between 2000 and 2010.
However, respiratory symptoms correlate poorly with
the presence or absence of objectively documented PE, and
as many as 75% of pulmonary emboli may be asymptom-
30,31
atic.
Routine diagnostic testing suggests that PE accompanies acute DVT much more frequently than is currently
appreciated. As many as 25%–52% of patients with documented DVT but no symptoms of PE will have high-probability lung scans at presentation.
as an unusual source of symptomatic PE, high-probability
scans have also been noted in 18%–29% of patients with isolated calf vein thrombosis.
28
e incidence of PE has substan-
29
30−33
Although regarded
17.4 The natural history of acuteDVT 207
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e outcomes aer PE vary with patient comorbidities
and presenting features. e American Heart Association
recommends stratifying patients into massive, sub-massive, and non-massive categories.34 Massive PE is characterized by sustained hypotension (systolic blood pressure
<90 mmHg), pulselessness, or persistent profound bradycardia; submassive PE by evidence of right ventricular
dysfunc tion (echocardiography, computed tomography,
brain natriuretic peptide [BNP or pro-BNP] or myocardial
necrosis [troponin I or T]); and non-massive PE by normotension with normal right ventricular (RV) function and
biomarkers. Mortality varies from 25% to 52.4% for massive
PE to approximately 1% for non-massive PE.
17.3.2 The post-thrombotic syndrome
e post-thrombotic syndrome, with symptoms including pain, edema, skin changes, and ulceration, is the most
important late complication of DVT. Older studies, many
with methodological aws, reported post-thrombotic manifestations in up to two-thirds of patients with an acute DVT.
More recent studies suggest that, although the incidence of
the post-thrombotic syndrome is still underappreciated, it
occurs less commonly than in historical studies. Among
224 patients followed for 5 years aer venographically conrmed DVT, the post-thrombotic syndrome developed in
29.6% of those with proximal thrombosis and 30% of those
with isolated calf vein thrombosis.35 Population-based
studies have suggested that skin changes and ulceration are
present in 6–7 million and 400,000–500,000 people in the
United States, respectively.36 In addition to the substantial
economic costs, the physical limitations of patients with
post-thrombotic symptoms are comparable to those of
patients with other serious chronic medical conditions.
27
17.3.3 Mortality after acute DVT
Mortality aer an episode of acute DVT exceeds that
expected in age-matched populations. Although the in-hospital case–fatality rate for DVT is only 5%, 1, 3, and 5-year
mortality rates of 22%, 30%, and 39%, respectively, have
been noted.
ary to cancer, PE, and cardiac disease. Among patients ≥45
years of age, cancer is the most important predictor of early
death,39 with 28-day mortality rates among those with cancer being as high as 25.4%.40 In comparison to the 12.6%
rate in patients without cancer, 1-year mortality rates are
as high as 63.4%.37 Although deaths among cancer patients
and those with idiopathic DVT remain high for at least 3
years beyond the index event, mortality rates for those with
secondary VTE unrelated to cancer return to those of the
general population aer 6 months.
DVT is also associated with an increased risk of cardiovascular morbidity and mortality.
tive risk of a symptomatic vascular event among patients
with idiopathic DVT is 25.4% in comparison to 12.9% in
those with secondary VTE.
27, 37,3 8
Early mortality is most frequently second-
37
41
e 10-year cumula-
42
Patients with idiopathic DVT
also have a higher prevalence of atherosclerotic risk factors
(diabetes, hypertension, and hypercholesterolemia) and
coronary artery calcium than controls without VTE.43 e
presence of residual thrombus at the time that anticoagulants are stopped may be a marker for subsequent cardiovascular events.
41,44
Patients with residual venous obstruction
3months aer a symptomatic DVT are 2.5-fold more likely
to develop recurrent VTE, post-thrombotic syndrome, cancer, or have an arterial thrombotic event.45 Although the
reasons for this are not clear, it has been postulated that the
presence of residual thrombus is associated with generalized hypercoagulability. Such a relationship is supported
by the higher levels of activated coagulation seen in DVT
patients with cardiac disease,46 and the observation that
delayed recanalization and myocardial infarction are both
associated with increased levels of plasminogen activator
inhibitor-1 (PAI-1).
47
17.4 THE NATURAL HISTORY OF
ACUTEDVT
17.4.1 Venous thrombogenesis
As initially proposed by Virchow, three factors are of primary importance in the development of venous thrombosis: abnormalities of blood ow, abnormalities of blood,
and vessel wall injury. However, despite the accuracy of
Virchow’s postulates, it is now apparent that all three components are not equally important in individual patients.
e role of structural injury to the venous wall is disputable; even in the presence of stasis, overt endothelial injury
appears to be neither a necessary nor sucient condition
for thrombosis.48 With the notable exceptions of direct
venous trauma, hip arthroplasty, and central venous catheters, there is little evidence that gross venous injury plays
a signicant role in most thromboses. In contrast, data are
accumulating that biological injury to the endothelium
may have a very important role in venous thrombogenesis. e venous endothelium is normally antithrombotic,
producing prostaglandin I2, thrombomodulin, tissue-type
plasminogen activator, and glycosaminoglycan cofactors
of antithrombin. Under conditions favoring thrombosis,
the endothelium may become pro-thrombotic, producing tissue factor, von Willebrand factor, and bronectin.
Leukocytes may be key mediators of both endothelial injury
and hypercoagulability, with the early phases of thrombosis
being marked by increases in permeability followed by leukocyte adhesion, migration, and endothelial disruption.
Associated cytokines may also be of importance, with factors such as interleukin-1 increasing tissue factor expression
while diminishing protein C activation.
51
Although most venous thrombi originate in areas of low
blood ow, stasis alone is also an inadequate stimulus in the
absence of low levels of activated coagulation factors.
Although stasis may facilitate endothelial leukocyte adhesion49 and cause endothelial hypoxia, leading to a pro-coagulant state,
54
its most important role may be in permitting
49,5 0
52,53
208 The clinical presentation and natural history of acute deep venous thrombosis
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the accumulation of activated coagulation factors in areas
that are prone to thrombosis. Stasis may thus be a permissive factor for the other events required for thrombosis.
Imbalanced activation of the coagulation system appears
to be the most important factor underlying many episodes
of acute DVT. Although the hemostatic system is continuously active, thrombus formation is ordinarily conned to
sites of local injury by a precise balance between activators
and inhibitors of coagulation and brinolysis. A pre-thrombotic state may result either from imbalances in the regulatory and inhibitory systems or from activation exceeding
antithrombotic capacity.55 Some component of imbalanced
coagulation appears to be associated with most thrombotic
risk factors, including age, malignancy, surgery, trauma,
primary hypercoagulable states, pregnancy, and oral contraceptive use.
Based on perceived dierences in their natural histories,
lower extremity venous thrombi are classied as involving the iliofemoral, femoropopliteal, or calf veins.3 ese
thrombi originate in areas where imbalanced coagulation
is localized by stasis: in the soleal sinuses, behind venous
valve pockets, at venous conuences, and distal to areas of
extrinsic compression. is is a very important and oen
misunderstood concept—DVT is fundamentally a disease
of coagulation localized to regions of stasis, rather than a
disease of the veins themselves. e calf veins are the most
common sites of origin, although 40% of proximal thrombi
arise primarily in the femoral or iliac veins. In the femoral
veins, these are presumably in regions behind the valves,56
while in the iliac veins, DVT is frequently associated with
compression of the le common iliac vein by the overlying right common iliac artery (May–urner syndrome).
In ow models, vortices produced beyond the valve cusps
tend to trap red cells in a low-shear eld near the apex of
the cusp.57 Such vortices have also been demonstrated in
vivo using B-ow ultrasound.58 Red cell aggregates form-
ing within these eddies are likely to be the early niduses of
thrombus formation.59 However, such aggregates are probably transient until stabilized by brin in the setting of
locally activated coagulation. Aer their formation, these
early thrombi may become anchored to the endothelium
near the apex of the valve cusp,
lated to be mediated by adherent leukocytes.
60, 61
a process that is postu-
50
Propagation of thrombi beyond areas of stasis probably
depends largely on the relative balance between activated
coagulation and thrombolysis. If local conditions favor
propagation, laminated appositional growth occurs outward from the apex as platelets are surrounded by a red
cell, brin, and leukocyte network. In contrast to arterial
thrombi, venous thrombi are composed largely of red cells
and brin, with relatively few platelets. Once luminal ow
is disturbed, prograde and retrograde propagation may also
be promoted by hemodynamic factors. Conversely, such
early thrombi may fail to propagate, with aborted thrombi
appearing as endothelialized brin fragments within the
valve pockets.
17.4.2 Recanalization
Once formed, the competing processes of recanalization
and recurrent venous thrombosis characterize the natural
history of acute DVT. e development of chronic sequelae
is closely related to the balance between these two processes.
e venous lumen is most oen re-established aer both
experimental and clinical thrombosis.62 e mechanisms
of thrombus organization and recanalization have been
extensively investigated in animal models of DVT. Both the
vein wall and thrombus play important roles in these processes. In short, there is rapid regeneration of a brinolytically active neoendothelium soon aer thrombosis, with an
early neutrophilic inltrate within the thrombus and vein
wall, followed by a predominantly monocyte inltrate.
Monocytes appear to play a particularly important role in
thrombus organization and recanalization, functioning
as a source of both brinolytic and cytokine mediators.
Experimental thrombi show complete recanalization by 3
weeks, with the thrombus reduced to an endothelialized
subintimal streak.
Although less extensively investigated, histologic studies suggest that clinical DVT follows a similar course. As in
the animal models, recanalization appears to be a complex
process involving intrinsic (arising within the thrombus)
and extrinsic brinolysis, peripheral fragmentation, neovascularization, and retraction. rombus organization
begins in the attachment zone with the migration of surfacing cells—presumably derived from the endothelium—over
the thrombus.
60
Pockets formed between the thrombus and
the vein walls then progressively enlarge through peripheral
fragmentation and brinolysis. e thrombus simultaneously undergoes central soening as well as contraction. In
the absence of propagation, the ultimate result is a restored
venous lumen with a slightly raised bro-elastic plaque at
the site of initial thrombus adherence to the vein wall.
Serial noninvasive diagnostic tests permitting venous
thrombi to be followed over time have conrmed the clinical
importance of these processes. Among 21 patients prospectively followed with ultrasound, Killewich etal.65 noted that
some recanalization was present by 7 days in 44% of patients
and by 90 days in 100% of patients. e percentage of initially
involved segments that remained occluded decreased to
means of 44% by 30 days and 14% by 90 days. van Ramshorst
etal.66 similarly noted an exponential decrease in thrombus
load over the rst 6 months aer femoropopliteal thrombosis. Most recanalization occurred within the rst 6 weeks,
with ow re-established in 87% of 23 completely occluded
segments during this interval. Approximately 55% of subjects will show complete recanalization within 6–9 months
67, 68
of thrombosis.
However, some reduction in thrombus
load may continue, albeit at a slower rate, for months to years
aer the acute event (Figure 17.1). Notably, clinical studies
assessing two-point compressibility in the common femoral and popliteal veins have demonstrated similar rates of
incomplete recanalization (49.4%) at 3 months.
45
63,64
17.4 The natural history of acuteDVT 209
Follow-up interval
Thrombus score
12
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10
8
6
4
2
0
Day 0 Day 3 Day 7 Day 14 1 month3 months 6 months 9 months1 year
Fig u r e 17.1 Boxplot showing reduction in thrombus score determined by serial ultrasound examinations over the first
year after deep venous thrombosis. Top, middle, and bottom lines of boxes represent the 75th, 50th (median), and 25th
percentiles, respectively. Closed squares show the means, with top and bottom error bars representing the 90th and 10th
percentiles, respectively. Progressive recanalization occurs with a reduction in mean thrombus score from 5.1 at the time
of presentation to 1.8 at 12 months. Mean percentage rates of recanalization were 52.4% at 6 months, 57.9% at 9 months,
and 58.8% at 12 months. (From Meissner MH etal. J Vasc Surg 2002;35:278–85. Reprinted with permission.)
Although thrombus resolution proceeds at a similar rate
in the femoropopliteal venous segments,66 some
47, 69
have
found more rapid clearance from the tibial segments, perhaps reecting the increased eciency of thrombolysis in
small veins. In contrast, recanalization of thrombosed iliac
segments is slower and more oen incomplete. Iliofemoral
venous patency rates may be as low as 24%, 18%, and 18% at
1, 3, and 5 years aer DVT.
70
e degree of recanalization is related to both the
degree of activated coagulation and brinolytic inhibition
(Figure 17.2). Recanalization is negatively correlated with
levels of thrombin activation products (prothrombin fragment 1 and 2) at the time of presentation.47 Others
47, 68
have
found higher PAI-1 levels in patients with poor thrombus
resolution. From a clinical perspective, more complete
recanalization has been reported in older patients, those
with asymptomatic post-operative thrombosis, and patients
with involvement of only one venous segment.71 Cancer is
associated with less complete recanalization. e presence
of a permanent risk factor has also been associated with an
11-fold higher risk of delayed recanalization.
72
rates depending on treatment, proximal or distal location of
thrombus, and duration of follow-up. Fortunately, standard
anticoagulation is very eective at preventing recurrent
VTE while on treatment. Among patients with proximal
DVT, recurrent thromboembolic events occurred in 5.2% of
patients treated with standard anticoagulation measures for
3 months,
73
in comparison to 47% of patients inadequately
treated with a 3-month course of low-dose subcutaneous
heparin.74 Others75 have reported a 7% rate of recurrent
VTE during 3 months of anticoagulant treatment. More
recent randomized comparisons of the direct thrombin
(dabigatran etexilate) and factor Xa inhibitors (rivaroxaban,
apixaban, and edoxaban) to warfarin have demonstrated
similar rates of recurrent VTE for the new anticoagulants
(2.1%–3.2%) and warfarin (1.8%–3.5%) over the initial 3–12
months of treatment.
76
As VTE is fundamentally a disease of disordered anticoagulation, either acute or chronic, it is not surprising that
most symptomatic events occur aer anticoagulation has
been stopped. e risk of recurrence is at least as great in
the contralateral as in the ipsilateral extremity.77 Sarasin
and Bounameaux78 calculated a theoretical recurrence rate
17.4.3 Recurrent venous thrombosis
of 0.9% per month aer discontinuing anticoagulant therapy for proximal DVT, similar to observed annual recur-
Recurrent thrombotic events compete with recanalization early aer an acute DVT. Most clinical studies have
included both symptomatic recurrent DVT and PE, with
rence rates of 7.0%–12.9%.
is highest over the rst 6–12 months aer the index event,
although cumulative rates are as high as 24% at 5 years and
39,44
e risk of recurrent VTE
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