Sage Journals: Discover world-class research

Abstract

We assessed the potential safety of withholding treatment of pulmonary embolism (PE) limited to subsegmental branches. Literature review showed that untreated patients with mostly subsegmental PE had no fatal recurrences in 1 to 3 months and no nonfatal recurrences of PE in 3 months. Patients with suspected PE who had nondiagnostic ventilation/perfusion lung scans, adequate cardiorespiratory reserve or low or moderate clinical probability, and negative serial noninvasive leg tests were shown not to require treatment. It appears safe, therefore, to withhold treatment of subsegmental PE providing (1) pulmonary–respiratory reserve is good; (2) no evidence of deep venous thrombosis (DVT) on serial testing; (3) major risk factor for PE was transient and no longer present; (4) no history of central venous catheterization or atrial fibrillation; and (5) willingness to return for serial venous ultrasound. After fully informing patients, some may choose to be treated and some may choose not to be treated.

Keywords

pulmonary embolism deep venous thrombosis anticoagulant therapy

Interest in subsegmental pulmonary embolism (PE) has intensified with the ability to show such apparent small PE with contrast-enhanced computed tomography (CT).¹ The clinical relevance of isolated subsegmental PE and the management of such patients are uncertain.¹ The diagnosis of isolated subsegmental PE is uncertain,² although images with thin-collimation multidetector CT are compelling.^3–5 The purpose of this article is to update evidence related to the diagnosis and management of isolated subsegmental PE.

Prevalence

Small PE at Autopsy

The existence of PE in small pulmonary artery branches is not a recent discovery. A detailed postmortem investigation of small PE was published in 1964.⁶ The authors used arteriography of the cannulated and inflated lungs following injection of a barium sulfate–gelatin–mercury mass or later by a gelatin–potassium iodide–barium sulfate preparation. This was followed by careful dissection and histological examination. Among the 34 patients with recent PE as a terminal event, the astounding observation at autopsy was that PE lodged in muscular arterial segments (0.1-1 mm diameter) in every case (34 of 34, 100%), in arterioles (0.03-0.1 mm) in 13 (38%) of 34, and in elastic arteries (≥1 mm diameter) in only 8 (24%) of 34. Conventional pulmonary angiography and CT pulmonary angiography would, at best, show only elastic pulmonary arterial branches (≥1 mm diameter). Only the minority of patients in this necropsy study, therefore, had PE of a size that one could hope to see with the best imaging techniques.

Small PE as a Cause of Chronic Thromboembolic Pulmonary Hypertension

Patients with chronic thromboembolic pulmonary hypertension may have (1) central organized thrombi in the main or lobar pulmonary arteries, (2) intimal thickening and fibrosis proximal to the segmental arteries, (3) disease with distal segmental and subsegmental arteries only, or (4) hypertensive distal vasculopathy without visible thromboembolic disease.⁷ These may occur alone or in combination.⁷ Disease of distal segmental and subsegmental arteries only was observed in about 12% of patients in this selected group who underwent operation for chronic thromboembolic pulmonary hypertension.⁷

Isolated Subsegmental PE

The reported prevalence of isolated subsegmental PE is shown in Table 1.^2,3,8–27 In Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II, with mostly 4-detector CT angiograms, 8 (4%) of 181 patients with PE showed isolated subsegmental PE.² We define isolated subsegmental PE as a PE shown on CT angiography that occurred in a subsegmental branch but no larger order of vessels. The subsegmental PE may involve one or more than one subsegmental branch.

Table 1.

Prevalence of Isolated Subsegmental PE on CT or Conventional Pulmonary Angiograms

References	Method	Isolated Subsegmental PE in Patients With Suspected PE (%)^a	Isolated Subsegmental PE in Patients With Acute PE (%)	Comments
Stein and Henry⁸	Pulmonary angiography	–	22/375 (6)
Goodman et al⁹	Pulmonary angiography	–	4/11 (36)	All patients had a nondiagnostic V/Q scan
Quinn et al¹⁰	Pulmonary angiography	2/60 (3)	2/30 (10)
Oser et al¹¹	Pulmonary angiography	–	23/76 (30)	20 subsegmental, 3 < subsegmental
Lette et al¹²	DSA	–	5/29 (17)
Diffin et al¹³	Pulmonary angiography	5/114 (4)	5/29 (17)
Cha et al¹⁴	CTA and pulmonary angiography		22/334 (7)
De Monye et al¹⁵	CTA and DSA	29/487 (6)	29/130 (22)
Van Strijen et al¹⁶	Single-detector CTA	28/460 (6)	28/121 (23)
Thomeer et al¹⁷	Single-detector CTA	2/510 (0.4)	2/121 (1.7)
Thomeer et al¹⁷	Multidetector CTA	21/356 (6)	21/96 (22)
Anderson et al¹⁸	Single and multidetector CTA	8/672 (1.2)	8/111 (7)
Perrier et al¹⁹	4- and 16-detector CTA	14/507 (3)	14/187 (7)
Nijkeuter et al²⁰	Single-detector	12/258 (5)	12/82 (15)
Nijkeuter et al²⁰	Multidetector CTA	98/1921 (5)	98/551(18)
Douma et al²¹	4-detector CTA	2/110 (2)	2/26 (8)
Douma et al²¹	64-detector CTA	5/107 (5)	5/24 (21)
Ghanima et al²²	4-detector CTA	–	6/99 (6)
Stein et al²	4-detector CTA	8/773 (1)	8/181 (4)	Positive predictive value 2/8 (25%)
Eyer et al²³	8- and 16-detector CTA	77/1435 (5)	77/283 (27)
Donato et al²⁴	16- and 64-detector CTA	115/10 453 (1)	115/1463 (8)
Kluge et al²⁵	16-detector CTA	12/65 (18)	12/19 (63)
Brunot et al³	16-detector CTA	9/384 (2)	9/75 (12)	κ, 0.56 (mod) to 0.85 (good)
Suh et al²⁶	16-detector CTA	17/1273 (1)	17/101 (17)	Included segmental; subsegmental and fifth order 1.0 to 3.8 mm diameter
Nazaroglu et al²⁷	64-detector CTA	12/274 (4)	12/77 (16)

Abbreviations: PE, pulmonary embolism; DSA, digital subtraction angiography; CTA, computed angiographic angiography; V/Q, ventilation/perfusion lung scan.

^a Excludes patients with noninterpretable tests.

Incidental PE

Incidental PE may be found in asymptomatic patients who undergo CT angiography for reasons other than suspected PE.^28–31 Ritchie et al, with 4- and 16-detector CT angiography, found unexpected PE in 28 (6%) of 487 patients who underwent contrast-enhanced CT for reasons other than suspected acute PE.³¹ Among these, isolated subsegmental PE was identified in 5 patients. Others,^29,32 with single-detector CT angiography, found unexpected PE in 1% to 2% and with 4-detector CT angiography found³⁰ unexpected PE in 3%. None of these investigators found isolated subsegmental PE.^28–30 Dexter, in a prior generation (P. D. Stein and J. E. Dalen, personal communication, 1964), and more recently Gurney suggested that one of the normal functions of the lung is to remove small emboli, which, if allowed to enter the arterial circulation, would have disastrous consequences.³³ Such PE would be completely asymptomatic. Thus, many small PE may be a normal part of existence and unrecognized until identified by CT angiography or autopsy.

Diagnosis

Wedge Pulmonary Angiography

With considerable effort, and a technique no longer used, it was possible to show intraluminal filling defects in pulmonary arterial branches of 1.5 to 2.0 mm diameter.³⁴ This was accomplished by wedge arteriography, where a 7F size (2.3 mm diameter) end-hole catheter was wedged into a pulmonary artery branch and 1.0 mL of contrast material was injected. Pulmonary branches of 0.2 mm diameter can be clearly shown. Short of this technique, with superselective injections into the pulmonary artery (not wedge injections) cutoffs of small branches and filling defects of branches not quite so small can be shown. Diminished arborization of peripheral pulmonary arterial branches is not necessarily indicative of microemboli and can be seen in severe lung disease.³⁵

Computed Tomographic Angiography

The positive predictive value of apparent isolated subsegmental PE in PIOPED II was only 2 (25%) of 8.² Of the 773 patients with complete data in PIOPED II,³⁶ 4-slice scans were used in 691 (89%); 8-slice scans in 37 (5%); and 16-slice scans in 45 (6%). Imaging with 64-detector CT may be more accurate, but there is no readily available reference test to establish this.

Review by Le Gal et al indicated that single or multiple subsegmental PE were identified more frequently in patients with suspected PE evaluated by multidetector CT angiography, 17 (2.2%) of 770, than with single-detector CT angiography,³⁷ 22 (1.0%) of 2232. Carrier et al, based on systematic review, found isolated subsegmental PE in 4.7% of patients with PE diagnosed by single-detector CT and in 9.4% of patients with PE diagnosed by multidetector PE.³² Ghaye, in a review of patients with confirmed PE, also reported more subsegmental PE identified with multidetector CT angiography than with single-detector angiography.⁵

Present day clinical experience is that the clot burden in patients with isolated subsegmental PE is small. Deep venous thrombosis (DVT) is usually absent in patients with PE limited to subsegmental branches.^26,27

Treatment and No Treatment

Outcome of Untreated Patients With Isolated Subsegmental PE

Only a few investigations have shown the outcome of untreated patients with isolated subsegmental PE (Table 2).^{14,23,24,38,39} The evidence suggesting that patients with subsegmental PE could do without treatment comes from small retrospective cohort series. Most untreated patients had no evidence of DVT. Pooled data in 105 untreated patients with mostly isolated subsegmental PE, but in some with PE in larger brunches, showed no fatal recurrences in 1 to 3 months.^{14,23,24,38,39} There were 0 (0%) of 58 nonfatal recurrences of PE in 3 months.^14,23,24,38 Major hemorrhage^24,39 from anticoagulants occurred in 7% to 8%.

Table 2.

Treatment With Anticoagulants Compared With No Treatment of Isolated Subsegmental Pulmonary Embolism

References	Method	Recurrent PE With Anticoagulants (%)	Fatal PE With Anticoagulants (%)	Major Bleed With Anticoagulants (%)	Recurrent PE, No Treatment (%)	Fatal PE, No Treatment (%)	DVT Excluded (%; Method)	Follow-up (months)
Eyer et al²³	8-, 16-detector CTA	0/40 (0)	0/40 (0)		0/20 (0)	0/20 (0)	20/20 (100; CTV)	3
Schultz et al³⁸	16-detector CTA				0/10 (0)^a	0/10 (0)^a	10/10 (100; CTV)	3
Donato et al²⁴	16-, 64-detector CTA	1/69 (1.4)	0/69 (0)	5/69 (7)	0/21 (0)	0/21 (0)	19-20/21 (90-95; US)	3
Cha et al¹⁴	16-, 64-detector CTA	0/12 (0)^b	0/12 (0)^b		0/7 (0)^b	0/7 (0)^b
Engelke et al³⁹	4-, 16-detector CTA			4/49 (8)		0/47 (0)^c	12/47 (34; US/venography)	1

Abbreviations: CTA, computed angiographic angiography; PE, pulmonary embolism; CTV, computed tomographic venography; US, ultrasound; DVT, deep venous thrombosis.

^a Most were subsegmental.

^b Approximate value.

^c Size of PE unstated.

Risk of Major Bleeding and Death From Anticoagulants

Meta-analysis of bleeding rates reported in 33 studies was performed.⁴⁰ Data included 10 757 patients with venous thromboembolism who were treated 4374 patient-years with vitamin K antagonists for at least 3 months (target international normalized ratio 2.0-3.0). Major bleeding occurred in 7% per year. Fatal bleeding occurred in 1.3% per year. The case fatality rate for major bleeding was 13.4%.⁴⁰ In the initial 3 months of treatment, major bleeding occurred in 2.1% and fatal bleeding occurred in 0.4%.⁴⁰ In the Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry, 1880 patients with PE were treated with anticoagulants.⁴¹ During the initial hospitalization, 0.2% died from bleeding. In general, therefore, 2 to 4 of 1000 patients died from anticoagulants in the first 3 months of anticoagulant therapy.

Possible Alternative to Treatment With Anticoagulants in Selected Patients

If some patients may not require treatment of PE with anticoagulants, what might be the characteristics of such a patient? The following seem to be a reasonable answer. (1) Adequate pulmonary–respiratory reserve, so if PE did recur, the likelihood is that it would not be fatal. Pulmonary–respiratory reserve was defined as adequate if none of the following were present: pulmonary edema, right ventricular failure, hypotension (systolic pressure <90 mm Hg), syncope, acute tachyarrhythmias, or respiratory failure shown by severely abnormal spirometry (forced expiratory volume in 1 second <1.0 L or vital capacity <1.5 L), or blood gas measurements (Po₂ <50 mm Hg or Pco₂ >45 mm Hg in room air).⁴² (2) No evidence of DVT, so that there is no apparent site for the formation of further venous thrombi that could embolize to the pulmonary arteries. (3) A major risk factor for PE that is no longer present, such as major surgery, trauma, and no continuing risk factor. (4) No history of central venous catheterization and no history of atrial fibrillation, so upper extremity DVT or a cardiac source of emboli would be unlikely. (5) A compliant and trustworthy patient who would return for serial noninvasive leg tests.

Hull et al introduced the concept that patients with suspected acute PE and nondiagnostic ventilation/perfusion lung scans, who have negative serial noninvasive tests of the lower extremities, do not require treatment with anticoagulants, provided cardiorespiratory reserve is adequate.⁴³ Others followed with the requirement that the pretest clinical probability of PE should be low or moderate.⁴⁴ Such untreated patients with unproven PE had a low (0.5%-0.6%) rate of PE on follow-up.^42,44

The strategy of withholding treatment of acute PE if serial ultrasonography is negative is based on the observation that PE arises from DVT of the lower extremities in most patients. The safety of withholding treatment in patients with suspected PE, providing serial leg tests are negative, supports this observation.^42,44 Autopsy showed DVT of the lower extremities in 80% to 97% of patients with PE.^45–48 Thrombosis confined to pelvic veins or inferior vena cava is uncommon, 3 (3%) of 105 in PIOPED II.²

Our finding⁴⁹ is that in the investigation⁴⁴ by Wells et al, 117 patients with PE may have been followed off-treatment. The rate of PE in 3 months would have been 3 (2.6%) of 117. This rate of recurrent PE was not higher than in patients treated with anticoagulants in PIOPED.⁵⁰ Among patients treated only with anticoagulants in PIOPED I, recurrent nonfatal PE, fatal recurrent PE or death from the initial PE occurred in 11 (3.7%) of 297 in the first 3 months.⁵⁰ Nearly the same results were shown among patients in the Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry (EMPEROR) after 30 days.⁴¹ Death or recurrent PE in 30 days occurred in 69 (3.7%) of 1880 patients, among whom 98% were treated only with anticoagulants.

Accuracy of Venous Ultrasound for Diagnosis of DVT in Assessment for No Treatment

Among 149 patients with acute PE diagnosed by a high-probability lung scan or positive pulmonary angiogram, bilateral B-mode gray-scale compression ultrasonography of the proximal leg veins showed DVT in 43 (29%) of 149 patients.⁵¹ Others showed DVT by B-mode compression ultrasound in 70 (43%) of 162 patients with PE diagnosed by a high-probability ventilation/perfusion lung scan⁴⁴ and in 35 (58%) of 60 patients diagnosed by a high-probability ventilation/perfusion lung scan in combination with a high clinical probability.⁴⁴ Based on autopsy data showing that on average, 92% of patients with PE had thrombi that originated in the lower extremities,^45–48 the sensitivity of compression ultrasound would seem to be limited. Pooled data with compression ultrasound of the proximal deep veins in patients with clinically suspected symptomatic acute DVT, using contrast venography as a reference standard, showed a sensitivity in 234 (92%) of 253 patients and specificity in 325 (98%) of 330 patients.^52–56

Pooled data with compression ultrasound in asymptomatic patients with a high risk of DVT, using contrast venography as a reference standard, showed sensitivity in 28 (55%) of 51 patients for proximal DVT.^57–59 Specificity was found in 456 (94%) of 485 patients.^57–59 More recently,⁶⁰ among patients who underwent hip or knee replacement and obligatory venography, the sensitivity of compression ultrasound for proximal DVT was only 21%. The low sensitivity may reflect that the venous thrombi are small, nonoccluding, or distal.⁶⁰ Sensitivity of ultrasound depends on the number of compression maneuvers performed.⁶¹

It would seem that detection of DVT by compression ultrasound is potentially the only limiting factor in withholding treatment in patients with PE. The issue is not if venous ultrasound is accurate, but if it is accurate enough to detect DVT of sufficient size to be an important risk of PE. The investigation by Wells et al suggests that this is the case.⁴⁴

Accuracy of CT Venography for Detecting DVT in Assessment for No Treatment

Computed tomography venography and compression ultrasound are diagnostically equivalent.³⁶ There was 95.5% concordance between CT venography and ultrasound for the diagnosis or exclusion of DVT.³⁶ Diagnostic results in patients with signs or symptoms of DVT, asymptomatic patients, and patients with a history of DVT were similar irrespective of whether CT venography or ultrasound was used. In PIOPED II, with mostly 4-detector CT, 43 (4%) of 1062 of CT venograms were eliminated due to quality issues or lack of reader consensus.³⁶ Others, with 64-detector CT, showed insufficient quality of CT venography in 35 (11%) of 306 patients.²⁷

Published Recommendations

Recommendations for antithrombotic therapy for PE in the American College of Chest Physicians Evidence-Based Practice Guidelines (8th Edition) were that patients with PE secondary to a transient (reversible) risk factor should be treated with a vitamin K antagonist for 3 months.⁶² For patients with unprovoked PE, it was recommended that treatment should be at least for 3 months and the risk–benefit ratio of long-term treatment should be considered.⁶² For patients with PE and cancer, treatment was recommended for 3 to 6 months and probably indefinitely or until the cancer is resolved. In patients who were unexpectedly found to have asymptomatic PE, recommendations were the same for initial and long-term anticoagulation as for comparable patients with symptomatic PE.⁶²

The Fleischner Society suggested that the clinical relevance of small peripheral PE and the need to administer anticoagulants in such patients is a subject of debate.⁶³ They suggested that in patients with small PE and no DVT, the risks associated with anticoagulant therapy outweigh the benefits. They emphasized that because isolated subsegmental PE may herald subsequent PE, negative findings on the study of the lower extremities are mandatory.⁶³

Conclusion

Based on these data, we suggest that patients with isolated subsegmental PE need not be treated with anticoagulants, provided they meet the following criteria. (1) Good pulmonary–respiratory reserve; (2) no evidence of DVT with serial leg tests; (3) a transient (reversible) major risk factor for PE that is no longer present; (4) no history of central venous catheterization and no history of atrial fibrillation; and (5) a compliant and trustworthy patient who would return for serial noninvasive leg tests. With the information in hand, a clinician can now have a meaningful dialogue with a patient on the advantages and disadvantages of treating their isolated subsegmental pulmonary emboli. Some patients may choose to be treated or choose not to be treated. Further research is needed to clarify the need for anticoagulant therapy for subsegmental PE. The criteria for selecting patients who may not require treatment need to be validated in a prospective investigation. Ideally, this information should be provided by a randomized controlled trial.

Footnotes

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The authors received no financial support for the research, authorship, and/or publication of this article.

References

Goodman

LR.

Small pulmonary emboli: what do we know?

Radiology. 2005;234(3):654–658.

Stein

Fowler

Goodman

. PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354(22):2317–2327.

Brunot

Corneloup

Latrabe

Montaudon

Laurent

Reproducibility of multi-detector spiral computed tomography in detection of sub-segmental acute pulmonary embolism. Eur Radiol. 2005;15(10):2057–2063.

Patel

Kazerooni

Cascade

PN.

Pulmonary embolism: optimization of small pulmonary artery visualization at multi-detector row CT. Radiology. 2003;227(2):455–460.

Ghaye

Peripheral pulmonary embolism on multidetector CT pulmonary angiography. JBR-BTR. 2007;90(2):100–108.

Smith

Dammin

Dexter

Postmortem arteriographic studies of the human lung in pulmonary embolization. JAMA. 1964;188:143–151.

Galiè

Kim

NH.

Pulmonary microvascular disease in chronic thromboembolic pulmonary hypertension. Proc Am Thorac Soc. 2006;3(7):571–576.

Stein

Henry

JW.

Prevalence of acute pulmonary embolism in central and subsegmental pulmonary arteries and relation to probability interpretation of ventilation/perfusion lung scans. Chest. 1997;111(5):1246–1248.

Goodman

Curtin

Mewissen

. Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: helical CT versus angiography. AJR Am J Roentgenol. 1995;164(6):1369–1374.

10.

Quinn

Lundell

Klotz

. Reliability of selective pulmonary arteriography in the diagnosis of pulmonary embolism. AJR Am J Roentgenol. 1987;149(3):469–471.

11.

Oser

Zuckerman

Gutierrez

Brink

JA.

Anatomic distribution of pulmonary emboli at pulmonary angiography: implications for cross-sectional imaging. Radiology. 1996;199(1):31–35.

12.

Lette

Cerino

Eybalin

Levasseur

Prevalence and clinical significance of solitary pulmonary sub-segmental microembolism. Nucl Med Rev Cent East Eur. 2004;7(1):39–42.

13.

Diffin

Leyendecker

Johnson

Zucker

Grebe

PJ.

Effect of anatomic distribution of pulmonary emboli on interobserver agreement in the interpretation of pulmonary angiography. AJR Am J Roentgenol. 1998;171:1085–1089.

14.

Cha

Shin

Lee

. Clinical characteristics of patients with peripheral pulmonary embolism. Respiration. 2010;80(6):500–508.

15.

de Monyé

van Strijen

Huisman

Kieft

Pattynama

PM.

Suspected pulmonary embolism: prevalence and anatomic distribution in 487 consecutive patients. Advances in new technologies evaluating the localisation of pulmonary embolism (ANTELOPE) group. Radiology. 2000;215(1):184–188.

16.

Van Strijen

De Monye

Kieft

Pattynama

Prins

Huisman

MV.

Accuracy of single-detector spiral CT in the diagnosis of pulmonary embolism: a prospective multicenter cohort study of consecutive patients with abnormal perfusion scintigraphy. J Thromb Haemost. 2005;3(1):17–25.

17.

Thomeer

Pattynama

Hartmann

Kieft

Van Strijen

MJ.

High incidence of isolated subsegmental pulmonary emboli on multi-slice spiral CT: a comparative clinical study. Thromb Haemost. 2006;95(5):914–915.

18.

Anderson

Kahn

Rodger

. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743–2753.

19.

Perrier

Roy

Sanchez

. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005;352(17):1760–1768.

20.

Nijkeuter

Kwakkel-van

Erp JM

Kruip

. Christopher study investigators. Incidence of diagnosis of subsegmental pulmonary emboli using multidetector row and single-detector row computed tomography. J Thromb Haemost. 2008;6(2):384–386.

21.

Douma

Hofstee

Schaefer-Prokop

. Comparison of 4- and 64-slice CT scanning in the diagnosis of pulmonary embolism. Thromb Haemost. 2010;103(1):242–246.

22.

Ghanima

Abdelnoor

Holmen

Nielssen

Sandset

PM.

The association between the proximal extension of the clot and the severity of pulmonary embolism (PE): a proposal for a new radiological score for PE. J Intern Med. 2007;261(1):74–81.

23.

Eyer

Goodman

Washington

Clinicians’ response to radiologists’ reports of isolated subsegmental pulmonary embolism or inconclusive interpretation of pulmonary embolism using MDCT. AJR Am J Roentgenol. 2005;184(2):623–628.

24.

Donato

Khoche

Santora

Wagner

Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thromb Res. 2010;126(4):e266–e270.

25.

Kluge

Luboldt

Bachmann

Acute pulmonary embolism to the subsegmental level: diagnostic accuracy of three MRI techniques compared with 16-MDCT. AJR Am J Roentgenol. 2006;187(1):W7–W14.

26.

Suh

Cronan

Healey

TT.

Dots are not clots: the over-diagnosis and over-treatment of PE. Emerg Radiol. 2010;17(5):347–352.

27.

Nazaroğlu

Ozmen

Akay

Kilinç

Bilici

64-MDCT pulmonary angiography and CT venography in the diagnosis of thromboembolic disease. AJR Am J Roentgenol. 2009;192(3):654–661.

28.

Winston

Wechsler

Salazar

Kurtz

Spirn

PW.

Incidental pulmonary emboli detected at helical CT: effect on patient care. Radiology. 1996;201(1):23–27.

29.

Gosselin

Rubin

Leung

Huang

Rizk

NW.

Unsuspected pulmonary embolism: prospective detection on routine helical CT scans. Radiology. 1998;208(1):209–215.

30.

Storto

Di Credico

Guido

Larici

Bonomo

Incidental detection of pulmonary emboli on routine MDCT of the chest. AJR Am J Roentgenol. 2005;184(1):264–267.

31.

Ritchie

McGurk

McCreath

Graham

Murchison

JT.

Prospective evaluation of unsuspected pulmonary embolism on contrast enhanced multidetector CT (MDCT) scanning. Thorax. 2007;62(6):536–540.

32.

Carrier

Righini

Wells

. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010;8(8):1716–1722.

33.

Gurney

JW.

No fooling around: direct visualization of pulmonary embolism. Radiology. 1993;188(3):618–619.

34.

Stein

PD.

Wedge arteriography for the identification of pulmonary emboli in small vessels. Am Heart J. 1971;82(5):618–623.

35.

Stein

Leu

Welch

Guenter

CA.

Patho physiology of the pulmonary circulation in emphysema associated with alpha1 antitrypsin deficiency. Circulation. 1971;43(2):227–239.

36.

Goodman

Stein

Matta

. CT venography and compression ultrasound are diagnostically equivalent: Data from PIOPED II. Am J Roentgen. 2007;189(5):1071–1076.

37.

Le Gal

Righini

Parent

van Strijen

Couturaud

Diagnosis and management of subsegmental pulmonary embolism. J Thromb Haemost. 2006;4(4):724–731.

38.

Schultz

Brasel

Washington

. Incidence of asymptomatic pulmonary embolism in moderately to severely injured trauma patients. J Trauma. 2004;56(4):727–731.

39.

Engelke

Rummeny

Marten

Pulmonary embolism at multi-detector row CT of chest: One-year survival of treated and untreated patients. Radiology. 2006;239(2):563–575.

40.

Linkins

Choi

Douketis

JD.

Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med. 2003;139(11):893–900.

41.

Pollack

Schreiber

Goldhaber

. Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol. 2011;57(6):700–706.

42.

Hull

Raskob

Ginsberg

. Noninvasive strategy for the treatment of patients with suspected pulmonary embolism. Arch Intern Med. 1994;154(3):289–297.

43.

Hull

Raskob

Coates

Panju

Gill

GJ.

A new noninvasive management strategy for patients with suspected pulmonary embolism. Arch Intern Med. 1989;149(11):2549–2555.

44.

Wells

Ginsberg

Anderson

. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med. 1998;129(12):997–1005.

45.

Sevitt

Gallagher

Venous thrombosis and pulmonary embolism: a clinico-pathological study in injured and burned patients. Br J Surg. 1961;48:475–489.

46.

Short

DS.

A survey of pulmonary embolism in a general hospital. Brit Med J. 1952;1(4762):790–796.

47.

Byrne

O’Neil

EE.

Fatal pulmonary emboli. A study of 130 autopsy-proven fatal emboli. Am J Surg. 1952;83(1):47–54.

48.

Cohn

Walsh

The incidence and anatomical site of origin of pulmonary emboli. Stanford Med Bull. 1946;4(3-4):97–99.

49.

Stein

Hull

Raskob

GE.

Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial noninvasive leg tests. Am J Med. 2000;109(4):301–306.

50.

Stein

Henry

Relyea

Untreated patients with pulmonary embolism: outcome, clinical and laboratory assessment. Chest. 1995;107(4):931–935.

51.

Turkstra

Kuijer

van Beek

Brandjes

ten Cate

Buller

HR.

Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism. Ann Intern Med. 1997;126(10):775–781.

52.

Cronan

Dorfman

Scola

Schepps

Alexander

Deep venous thrombosis: US assessment using vein compression. Radiology. 1987;162(1 pt 1):191–194.

53.

Pedersen

Aslaksen

Vik-Mo

Bassoe

AM.

Compression ultrasonography in hospitalized patients with suspected deep venous thrombosis. Arch Intern Med. 1991;151(11):2217–2220.

54.

Lensing

Prandoni

Brandjes

. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med. 1989;320(6):342–345.

55.

O’Leary

Kane

Chase

BM.

A prospective study of the efficacy of B-scan sonography in the detection of deep venous thrombosis in the lower extremities. J Clin Ultrasound. 1988;16(1):1–8.

56.

Lewis

James

Welch

Joyce

Hallett

Weaver

AL.

Diagnosis of acute deep venous thrombosis of the lower extremities: prospective evaluation of color doppler flow imaging versus venography. Radiology. 1994;192(3):651–655.

57.

Froehlich

Dorfman

Cronan

Urbanek

Herndon

Aaron

RK.

Compression ultrasonography for the detection of deep venous thrombosis in patients who have a fracture of the hip. A prospective study. J Bone Joint Surg Am. 1989;71(2):249–256.

58.

Davidson

Elliott

Lensing

AW.

Low accuracy of color doppler ultrasound in the detection of proximal leg vein thrombosis in asymptomatic high-risk patients. The RD Heparin Arthroplasty Group. Ann Intern Med. 1992;117:735–738.

59.

Lensing

Doris

McGrath

. A comparison of compression ultrasound with color doppler ultrasound for the diagnosis of symptomless postoperative deep vein thrombosis. Arch Intern Med. 1997;157(7):765–768.

60.

Schellong

Beyer

Kakkar

. Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS study. J Thromb Haemost. 2007;5(7):1431–1437.

61.

Beyer-Westendorf

Halbritter

Platzbecker

. Central adjudication of venous ultrasound in VTE screening trials-reasons for failure. J Thromb Haemost. 2010;9(3):457–463.

62.

Kearon

Kahn

Agnelli

. American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):454S–545S.

63.

Remy-Jardin

Pistolesi

Goodman

. Management of suspected acute pulmonary embolism in the era of CT angiography: a statement from the Fleischner society. Radiology. 2007;245(2):315–329.

Diagnosis and Management of Isolated Subsegmental Pulmonary Embolism: Review and Assessment of the Options

Abstract

Keywords

Prevalence

Small PE at Autopsy

Small PE as a Cause of Chronic Thromboembolic Pulmonary Hypertension

Isolated Subsegmental PE

Incidental PE

Diagnosis

Wedge Pulmonary Angiography

Computed Tomographic Angiography

Treatment and No Treatment

Outcome of Untreated Patients With Isolated Subsegmental PE

Risk of Major Bleeding and Death From Anticoagulants

Possible Alternative to Treatment With Anticoagulants in Selected Patients

Accuracy of Venous Ultrasound for Diagnosis of DVT in Assessment for No Treatment

Accuracy of CT Venography for Detecting DVT in Assessment for No Treatment

Published Recommendations

Conclusion

Footnotes

References