Thrombosis Research 134 (2014) 1182–1185
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
NATF Corner Review Article
Silent pulmonary embolism in patients with distal deep venous thrombosis: Systematic review Mary J. Hughes, Paul D. Stein ⁎, Fadi Matta Department of Osteopathic Medical Specialties, Michigan State University College of Osteopathic Medicine, East Lansing, Michigan, United States
a r t i c l e
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a b s t r a c t Purpose: The purpose of this investigation was to determine the prevalence of silent pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) limited to the calf veins. Methods: This is a systematic review. We attempted to identify all published investigations that reported the prevalence of silent PE in patients with infrapopliteal DVT. Studies were identified by searching PubMed through January 2014. The search was augmented by manually reviewing the references in all original articles and in reviews. Results: The prevalence of silent PE in patients with DVT limited to the calf veins was described in 6 investigations. Pooled data showed a prevalence of 24 of 183 (13.1%) (95% CI 8.9-18.8%). Conclusion: Silent PE in patients with DVT limited to the calf veins is not rare. Imaging at the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may be useful, but there is an economic cost and exposure to radiation. © 2014 Elsevier Ltd. All rights reserved.
Article history: Received 28 July 2014 Received in revised form 15 September 2014 Accepted 24 September 2014 Available online 2 October 2014
Contents Introduction . . . . . Methods . . . . . . Statistical methods Results . . . . . . . Discussion . . . . . . Financial disclosure . . References . . . . . .
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Introduction Silent pulmonary embolism (PE) has been diagnosed in living patients with deep venous thrombosis (DVT) since the early 1970’s [1,2]. The possibility of silent PE in patients with DVT limited to the distal leg veins raises important clinical questions. Should patients with distal DVT undergo pulmonary imaging even if they have no respiratory symptoms? Should routine screening be performed to prevent a misdiagnosis of subsequently developing PE presumed to result from treatment failure in patients with distal DVT? Might unnecessary insertion of an inferior vena cava filter be avoided if it were known that silent PE had been present, and there was no failure of treatment of DVT?
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1182 1182 1183 1183 1183 1184 1184
Imaging at the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may prevent a misdiagnosis of PE occurring as a result of failed anticoagulant therapy. Such a misdiagnosis could lead to unnecessary insertion of an inferior vena cava filter. Whether routine imaging for PE in patients with DVT limited to the distal veins would be appropriate depends, in part, on the prevalence of silent PE in such patients. This information will help physicians make an informed decision in the management of patients with distal DVT. The goal of this investigation is to determine the prevalence of silent PE in patients with DVT limited to the calf veins.
Methods ⁎ Corresponding author at: Michigan State University, College of Osteopathic Medicine, Detroit Medical Center, 4707 St Antoine- Box 402, Detroit, MI 48201. Tel.: +1 248 701 7210; fax: +1 313 578 9601. E-mail address: [email protected] (P.D. Stein).
http://dx.doi.org/10.1016/j.thromres.2014.09.036 0049-3848/© 2014 Elsevier Ltd. All rights reserved.
This is a systematic review. We attempted to identify all published investigations in all languages that reported the prevalence of silent PE in patients with distal DVT, defined as infrapopliteal DVT.
M.J. Hughes et al. / Thrombosis Research 134 (2014) 1182–1185
Investigations were included if they met the following criteria: 1) The methods of diagnosis of PE and of DVT were described, 2) DVT was infrapopliteal, 3) DVT was diagnosed by compression ultrasound, conventional contrast venography, computed tomographic (CT) venography, or magnetic resonance imaging (MRI), 4) the PE was stated to be asymptomatic, 5) data permitted calculation of the prevalence of silent PE with distal DVT. Investigations were identified by searching PubMed through January 2014. Key words were silent, incidental, symptomless, and occult pulmonary embolism combined with deep venous thrombosis. Additional searches were silent pulmonary embolism combined with calf venous thrombosis or distal vein thrombosis. We augmented our search by manually reviewing the references in all original articles and reviews. The literature search identified 222 citations. Complete versions of the articles were obtained if the title or abstract suggested that they satisfied the inclusion criteria. Among these, 154 were unrelated to silent PE with DVT, 11 related to silent PE only with proximal DVT or site not stated, 3 diagnosed DVT by methods other than compression ultrasound, CT venography, conventional contrast venography, or MRI, 1 defined DVT as including the distal portion of the popliteal vein, 4 were case reports, 3 were case series without data on the prevalence of silent PE with distal DVT, 3 were related reviews, editorials, or guidelines, (and 2 duplicates), 34 were unrelated reviews, editorials, or guidelines, 1 related to silent PE in circumstances other than patients with DVT. The literature search identified 4 investigations that met the inclusion criteria (plus 2 duplicates). An additional 2 investigations were identified from the references in these investigations and from a review article of antithrombotic therapy. Statistical methods 95% confidence intervals (CI) were calculated according to the modified Wald method using GraphPad QuickCalcs for confidence intervals (http://graphpad.com/quickcalcs/confInterval2/). Results The prevalence of silent PE in patients with distal DVT was described in 6 investigations [3–8] (Table 1). Individual investigations included b67 patients with distal DVT and b7 with silent PE. Pooled data showed a prevalence of 24 of 183 (13.1%) (95% CI 8.918.8%). An example of a CT pulmonary angiogram showing PE in a patient with distal DVT and no pulmonary symptoms is shown (Figs. 1-3). Discussion The prevalence of silent PE in patients with distal DVT was 13.1%. Patients with silent PE may develop symptoms during the course of therapy without developing a recurrent PE [9]. The prevalence of silent PE in patients with distal DVT that we estimated is less than the prevalence of
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Fig. 1. CT pulmonary angiogram, transverse view, showing bilateral pulmonary emboli (arrows) in a patient with distal DVT and no pulmonary symptoms.
silent PE in patients with proximal DVT, 891 of 2,807 (32%), but still a substantial proportion [10]. An odds ratio of silent PE in those with proximal DVT compared to distal DVT has been reported as 3.6 [3]. In an investigation of proximal DVT that extended into the pelvic veins, 69 of 139 (50%) showed silent PE [11]. The finding of a higher proportion of patients with proximal DVT having silent PE than those with distal DVT is concordant with the observation that patients with proximal DVT are more likely to suffer symptomatic PE than those with distal DVT [12]. The importance of this investigation relates to the observation that silent PE in patients with calf vein DVT is not rare. Management and prognosis may differ from DVT alone in those with silent PE. In patients with isolated distal DVT, treatment with anticoagulants may not be necessary if the patient does not have severe symptoms or risk factors for extension [13]. Such patients may be followed with serial imaging of the deep veins [13]. On the other hand, patients with silent PE should be treated with anticoagulants in the same way as those with symptomatic PE [13]. Screening for silent PE in patients with DVT may be particularly useful in those with a contraindication for anticoagulation [14] and we believe in those with a high risk for anticoagulation. A recurrent PE is more frequent than a new PE in patients with DVT alone. When patients with PE were compared to patients with DVT alone, the relative risk of rehospitalization within 6 months with a diagnosis of PE was 4.2 [15]. Others also found that recurrent PE was more frequent in patients with PE on admission than a new PE in those with DVT alone, 18 of 151 (11.9%) versus 3 of 155 (1.9%) [16]. This is true
Table 1 Silent Pulmonary Embolism in Patients with Distal Deep Venous Thrombosis. First Author, Year (Reference)
Method for Diagnosis of DVT
Method for Diagnosis of PE
Li 2013 [3]
CT Venography or Ultrasound Ultrasound or Venography Ultrasound Venography Venography Venography
CT Angiogram
7/67(10.4)
High probability V/Q scan (PIOPED criteria) [16] Angiogram if not high probability V/Q scan CT Angiogram High probability V/Q scan (Biello criteria) [17] High probability V/Q scan V/Q scan, serial Q scan or conventional pulmonary angiogram
3/41 (7.3)
Martin, 1995 [4] Lopez-Beret, 2001 [5] Monreal 1992 [6] Nielsen, 1994 [7] Moreno-Cabral, 1976 [8] TOTAL
DVT = deep venous thrombosis, PE = pulmonary embolism, V/Q = ventilation/perfusion, Q = perfusion.
Silent PE n/N (%)
3/8 (37.5) 1/25 (4.0) 5/15 (33.3) 5/27 (18.5) 24/183 (13.1)
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Fig. 2. CT pulmonary angiogram, coronal view, same patient as Fig. 1. Pulmonary embolism on left is shown (arrow).
for silent PE as well. Recurrent PE in patients with DVT and silent PE was more frequent than an occurrence of PE in patients with DVT who did not have silent PE, 9 of 258 (3.5%) versus 4 of 742 (0.5%) (odds ratio 6.5) [17]. Others showed that DVT patients with silent PE at baseline had an increased incidence of PE events during the first 15 days of anticoagulant therapy, 8 of 822 (0.97%) versus 3 of 1496 (0.20%) (odds ratio 4.80 [14]. In view of such observations, Murin et al stated that DVT and PE appear to be distinct albeit overlapping clinical entities with different natural histories [15]. Lung scans in patients with symptomatic DVT and no clinical suspicion of PE may be useful, since some patients with silent PE may develop symptoms while on heparin therapy [9]. Monreal et al showed that 6 of 200 patients with DVT and silent PE developed symptoms during 7-day follow-up, but no new perfusion defects were found on repeated lung scan [9]. Without baseline scintigraphy all of these patients would have been considered to have recurrent PE, and vena cava interruption could have been performed because of a perceived failure of anticoagulants [9]. Silent PE may lead to pulmonary hypertension. The prevalence of chronic thromboembolic pulmonary hypertension after treatment for symptomatic acute PE in recent years has been reported to be 3.8% - 5.4% [18,19]. Without treatment, the prevalence of chronic thromboembolic pulmonary hypertension in patients with silent PE would be higher, because of a failure to prevent recurrent pulmonary embolism.
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The strength of this investigation is that it summarizes all data that use modern diagnostic techniques for DVT and PE to determine the prevalence of silent PE in patients with DVT limited to the calf veins. The data obtained comprise the most information compiled on this subject. Some of us previously determined the prevalence of silent PE in patients with DVT [10]. Distal DVT was defined similarly (infrapopliteal) in our previous investigation, except in one study, distal DVT included the distal portion of the popliteal vein [20]. The prevalence of silent PE that we now show in patients with distal DVT, 13.1%, is nearly identical to the prevalence that we showed previously, 15 of 113 (13.3%), and we now have data on 62% more patients [10]. Limitations include an inability to determine the size of the silent PE and the relation of silent PE to age, associated illness or clinical features due to the small number of patients in individual investigations. Another limitation is heterogeneity of the methods used for detection of silent PE, including different criteria for interpretation of the ventilation/ perfusion lung scans [21,22]. Imaging for silent PE in patients with calf vein DVT can be obtained with low exposure to radiation in most patients by using perfusion scintigraphy without ventilation scintigraphy [23]. The effective dose of 99mTc-MAA (macro aggregated albumin) perfusion lung scan is 0.68-2.04 mSv [24]. A ventilation scan with 81Kr would add 0.0280.28 mSv [25] and a ventilation scan with 99m Tc-DTPA (diethylene triamine pentaacetic acid) would add 0.14-0.21 mSv [24]. The effective dose of radiation with pulmonary scintigraphy is less than with CT pulmonary angiography. The average effective dose for 4-16 detector CT is 5.4 mSv based on computed data [26]. A measured effective dose of 19.9 + 1.38 mSv with 64-detector CT has been reported [27]. Breast doses were decreased from 62 mGy to 33 mGy with bismuth shields, but the effect of increased noise on the ability to diagnosis PE was not assessed [28]. Perfusion scintigraphy alone in patients with a normal or nearly normal chest radiograph can provide diagnostic accuracy similar to CT pulmonary angiography and ventilation/perfusion scintigraphy [23]. Chest radiographs were normal or nearly normal in 72% of patients with suspected PE, allowing a diagnosis or exclusion of PE by a perfusion scan alone [23]. Most patients with DVT, therefore, could be evaluated for silent PE with a perfusion scan alone. Those with lung disease, however, would require computed tomographic (CT) pulmonary angiography. If perfusion lung scans are not immediately available on the emergency service, it would be reasonable to obtain the scan the next day. The costs of routine screening for silent PE in patients with isolated calf DVT are a consideration as well as exposure to ionizing radiation, to which most patients would be exposed with no benefit. On the other hand, those in whom silent PE is identified could be treated knowledgeably with anticoagulants, rather than being followed for proximal extension of the thrombus. Dangers of an incorrect diagnosis of failure of treatment would be eliminated with baseline imaging. In conclusion, silent PE in patients with DVT limited to the calf veins is not rare. Imaging at the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may be useful, but there is an economic cost and exposure to radiation.
Financial disclosure The authors have no financial or other potential conflicts of interest relative to the data in this manuscript.
References
Fig. 3. CT pulmonary angiogram, coronal view, same patient as Fig. 1. Pulmonary embolism on right is shown (arrow).
[1] Kistner RL, Ball JJ, Nordyke RA, Freeman GC. Incidence of pulmonary embolism in the course of thrombophlebitis of the lower extremities. Am J Surg 1972;124:169–76. [2] Browse NL, Clemenson G, Croft DN. Fibrinogen-detectable thrombosis in the legs and pulmonary embolism. Br Med J 1974;1:603–4.
M.J. Hughes et al. / Thrombosis Research 134 (2014) 1182–1185 [3] Li F, Wang X, Huang W, Ren W, Cheng J, Zhang MO, et al. Risk factors associated with the occurrence of silent pulmonary embolism in patients with deep venous thrombosis of the lower limb. Phlebology May 9 2013 [Epub ahead of print]. [4] Martin F, Leroyer C, Oger E, Bressollette L, Andre N, Nonent M, et al. Pulmonary embolism and the level of thrombosis. A prospective study of 155 patients. Rev Mal Respir 1995;12:465–9. [5] López-Beret P, Pinto JM, Romero A, Orgaz A, Fontcuberta J, Oblas M, et al. Systematic study of occult pulmonary thromboembolism in patients with deep venous thrombosis. J Vasc Surg 2001;33:515–21. [6] Monreal M, Ruíz J, Olazabal A, Arias A, Roca J. Deep venous thrombosis and the risk of pulmonary embolism. A systematic study. Chest 1992;102:677–81. [7] Nielsen HK, Husted SE, Krusell LR, Fasting H, Charles P, Hansen HH. Silent pulmonary embolism in patients with deep venous thrombosis. Incidence and fate in a randomized controlled trial of anticoagulation versus no anticoagulation. J Intern Med 1994; 235:457–61. [8] Moreno-Cabral R, Kistner RL, Nordyke RA. Importance of calf vein thrombophlebitis. Surgery 1976;80:735–42. [9] Monreal M, Ruiz J, Fraile M, Bonet B, Davant E, Muchart J, et al. Prospective study on the usefulness of lung scan in patients with deep vein thrombosis of the lower limbs. Thromb Haemost 2001;85:771–4. [10] Stein PD, Matta F, Musani MH, Diaczok B. Silent pulmonary embolism in patients with deep venous thrombosis: A systematic review. Am J Med 2010;123:426–31. [11] Partsch H, Oburger K, Mostbeck A, König B, Köhn H. Frequency of pulmonary embolism in ambulant patients with pelvic vein thrombosis: a prospective study. J Vasc Surg 1992;16:715–22. [12] Moser KM, LeMoine JR. Is embolic risk conditioned by location of deep venous thrombosis? Ann Intern Med 1981;94:439–44. [13] Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schünemann HJ. American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl.):7S–47S. [14] Tzoran I, Saharov G, Brenner B, Delsart D, Roman P, Visona A, et al. RIETE Investigators. Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs. J Thromb Haemost 2012;10:564–71. [15] Murin S, Romano PS, White RH. Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost 2002;88: 407–14. [16] Monreal M, Lafoz E, Ruiz J, Arias A. Recurrent pulmonary embolism in patients treated because of acute venous thromboembolism: a prospective study. Eur J Vasc Surg 1994;8:584–9.
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[17] Monreal M, Büller H, Lensing AW, Bonet M, Roncales J, Muchart J, et al. Should patients with deep vein thrombosis alone be treated as those with concomitant asymptomatic pulmonary embolism? A prospective study. Thromb Haemost 2002; 88:938–42. [18] Guerin L, Couturaud F, Parent F, Revel MP, Gillaizeau F, Planquette B, et al. Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Thromb Haemost 2014;112 [Epub ahead of print]. [19] Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al. Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary Embolism. N Engl J Med 2004;350: 2257–64. [20] Dorfman GS, Cronan JJ, Tupper TB, Messersmith RN, Denny DF, Lee CH. Occult pulmonary embolism: a common occurrence in deep venous thrombosis. AJR Am J Roentgenol 1987;148:263–6. [21] Collaborative Study by the PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: Results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). J Am Med Assoc 1990;263:2753–9. [22] Biello DR. Radiological (scintigraphic) evaluation of patients with suspected pulmonary thromboembolism. J Am Med Assoc 1987;257:3257–9. [23] Sostman HD, Miniati M, Gottschalk A, Matta F, Stein PD, Pistolesi M. Sensitivity and specificity of perfusion scintigraphy combined with chest radiography for diagnosing pulmonary embolism. J Nucl Med 2008;49:1741–8. [24] ICRP. Radiation dose to patients from radiopharmaceuticals (ICRP publication 80, addendum 2 to ICRP 53). Ann ICRP 1998;28:1–126. [25] Camps JA, Zuur C, Blokland JA, Broerse JJ, Pauwels EK. A breathing lung phantom for 81mKr lung ventilation studies its use in dosimetry and quality control. Eur J Nucl Med 1988;14:529–32. [26] Valentine J. International Commission on Radiation Protection. Managing patient dose in multi-detector computed tomography (MDCT). ICRP Publication 102. Ann ICRP 2007;37:1–79. [27] Hurwitz LM, Reiman RE, Yoshizumi TT, Goodman PC, Toncheva G, Nguyen G, et al. Radiation dose from contemporary cardiothoracic multidetector CT protocols with an anthropomorphic female phantom. Implications for cancer induction. Radiology 2007;245:742–50. [28] Hurwitz LM, Yoshizumi TT, Goodman PC, Nelson RC, Toncheva G, Nguyen GB, et al. Radiation dose savings for adult pulmonary embolus 64 MDCT using bismuth breast shields, lower peak kilovoltage, and automatic tube current modulation. AJR Am J Roentgenol 2009;192:244–53.
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
NATF Corner Review Article
Silent pulmonary embolism in patients with distal deep venous thrombosis: Systematic review Mary J. Hughes, Paul D. Stein ⁎, Fadi Matta Department of Osteopathic Medical Specialties, Michigan State University College of Osteopathic Medicine, East Lansing, Michigan, United States
a r t i c l e
i n f o
a b s t r a c t Purpose: The purpose of this investigation was to determine the prevalence of silent pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) limited to the calf veins. Methods: This is a systematic review. We attempted to identify all published investigations that reported the prevalence of silent PE in patients with infrapopliteal DVT. Studies were identified by searching PubMed through January 2014. The search was augmented by manually reviewing the references in all original articles and in reviews. Results: The prevalence of silent PE in patients with DVT limited to the calf veins was described in 6 investigations. Pooled data showed a prevalence of 24 of 183 (13.1%) (95% CI 8.9-18.8%). Conclusion: Silent PE in patients with DVT limited to the calf veins is not rare. Imaging at the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may be useful, but there is an economic cost and exposure to radiation. © 2014 Elsevier Ltd. All rights reserved.
Article history: Received 28 July 2014 Received in revised form 15 September 2014 Accepted 24 September 2014 Available online 2 October 2014
Contents Introduction . . . . . Methods . . . . . . Statistical methods Results . . . . . . . Discussion . . . . . . Financial disclosure . . References . . . . . .
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Introduction Silent pulmonary embolism (PE) has been diagnosed in living patients with deep venous thrombosis (DVT) since the early 1970’s [1,2]. The possibility of silent PE in patients with DVT limited to the distal leg veins raises important clinical questions. Should patients with distal DVT undergo pulmonary imaging even if they have no respiratory symptoms? Should routine screening be performed to prevent a misdiagnosis of subsequently developing PE presumed to result from treatment failure in patients with distal DVT? Might unnecessary insertion of an inferior vena cava filter be avoided if it were known that silent PE had been present, and there was no failure of treatment of DVT?
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1182 1182 1183 1183 1183 1184 1184
Imaging at the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may prevent a misdiagnosis of PE occurring as a result of failed anticoagulant therapy. Such a misdiagnosis could lead to unnecessary insertion of an inferior vena cava filter. Whether routine imaging for PE in patients with DVT limited to the distal veins would be appropriate depends, in part, on the prevalence of silent PE in such patients. This information will help physicians make an informed decision in the management of patients with distal DVT. The goal of this investigation is to determine the prevalence of silent PE in patients with DVT limited to the calf veins.
Methods ⁎ Corresponding author at: Michigan State University, College of Osteopathic Medicine, Detroit Medical Center, 4707 St Antoine- Box 402, Detroit, MI 48201. Tel.: +1 248 701 7210; fax: +1 313 578 9601. E-mail address: [email protected] (P.D. Stein).
http://dx.doi.org/10.1016/j.thromres.2014.09.036 0049-3848/© 2014 Elsevier Ltd. All rights reserved.
This is a systematic review. We attempted to identify all published investigations in all languages that reported the prevalence of silent PE in patients with distal DVT, defined as infrapopliteal DVT.
M.J. Hughes et al. / Thrombosis Research 134 (2014) 1182–1185
Investigations were included if they met the following criteria: 1) The methods of diagnosis of PE and of DVT were described, 2) DVT was infrapopliteal, 3) DVT was diagnosed by compression ultrasound, conventional contrast venography, computed tomographic (CT) venography, or magnetic resonance imaging (MRI), 4) the PE was stated to be asymptomatic, 5) data permitted calculation of the prevalence of silent PE with distal DVT. Investigations were identified by searching PubMed through January 2014. Key words were silent, incidental, symptomless, and occult pulmonary embolism combined with deep venous thrombosis. Additional searches were silent pulmonary embolism combined with calf venous thrombosis or distal vein thrombosis. We augmented our search by manually reviewing the references in all original articles and reviews. The literature search identified 222 citations. Complete versions of the articles were obtained if the title or abstract suggested that they satisfied the inclusion criteria. Among these, 154 were unrelated to silent PE with DVT, 11 related to silent PE only with proximal DVT or site not stated, 3 diagnosed DVT by methods other than compression ultrasound, CT venography, conventional contrast venography, or MRI, 1 defined DVT as including the distal portion of the popliteal vein, 4 were case reports, 3 were case series without data on the prevalence of silent PE with distal DVT, 3 were related reviews, editorials, or guidelines, (and 2 duplicates), 34 were unrelated reviews, editorials, or guidelines, 1 related to silent PE in circumstances other than patients with DVT. The literature search identified 4 investigations that met the inclusion criteria (plus 2 duplicates). An additional 2 investigations were identified from the references in these investigations and from a review article of antithrombotic therapy. Statistical methods 95% confidence intervals (CI) were calculated according to the modified Wald method using GraphPad QuickCalcs for confidence intervals (http://graphpad.com/quickcalcs/confInterval2/). Results The prevalence of silent PE in patients with distal DVT was described in 6 investigations [3–8] (Table 1). Individual investigations included b67 patients with distal DVT and b7 with silent PE. Pooled data showed a prevalence of 24 of 183 (13.1%) (95% CI 8.918.8%). An example of a CT pulmonary angiogram showing PE in a patient with distal DVT and no pulmonary symptoms is shown (Figs. 1-3). Discussion The prevalence of silent PE in patients with distal DVT was 13.1%. Patients with silent PE may develop symptoms during the course of therapy without developing a recurrent PE [9]. The prevalence of silent PE in patients with distal DVT that we estimated is less than the prevalence of
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Fig. 1. CT pulmonary angiogram, transverse view, showing bilateral pulmonary emboli (arrows) in a patient with distal DVT and no pulmonary symptoms.
silent PE in patients with proximal DVT, 891 of 2,807 (32%), but still a substantial proportion [10]. An odds ratio of silent PE in those with proximal DVT compared to distal DVT has been reported as 3.6 [3]. In an investigation of proximal DVT that extended into the pelvic veins, 69 of 139 (50%) showed silent PE [11]. The finding of a higher proportion of patients with proximal DVT having silent PE than those with distal DVT is concordant with the observation that patients with proximal DVT are more likely to suffer symptomatic PE than those with distal DVT [12]. The importance of this investigation relates to the observation that silent PE in patients with calf vein DVT is not rare. Management and prognosis may differ from DVT alone in those with silent PE. In patients with isolated distal DVT, treatment with anticoagulants may not be necessary if the patient does not have severe symptoms or risk factors for extension [13]. Such patients may be followed with serial imaging of the deep veins [13]. On the other hand, patients with silent PE should be treated with anticoagulants in the same way as those with symptomatic PE [13]. Screening for silent PE in patients with DVT may be particularly useful in those with a contraindication for anticoagulation [14] and we believe in those with a high risk for anticoagulation. A recurrent PE is more frequent than a new PE in patients with DVT alone. When patients with PE were compared to patients with DVT alone, the relative risk of rehospitalization within 6 months with a diagnosis of PE was 4.2 [15]. Others also found that recurrent PE was more frequent in patients with PE on admission than a new PE in those with DVT alone, 18 of 151 (11.9%) versus 3 of 155 (1.9%) [16]. This is true
Table 1 Silent Pulmonary Embolism in Patients with Distal Deep Venous Thrombosis. First Author, Year (Reference)
Method for Diagnosis of DVT
Method for Diagnosis of PE
Li 2013 [3]
CT Venography or Ultrasound Ultrasound or Venography Ultrasound Venography Venography Venography
CT Angiogram
7/67(10.4)
High probability V/Q scan (PIOPED criteria) [16] Angiogram if not high probability V/Q scan CT Angiogram High probability V/Q scan (Biello criteria) [17] High probability V/Q scan V/Q scan, serial Q scan or conventional pulmonary angiogram
3/41 (7.3)
Martin, 1995 [4] Lopez-Beret, 2001 [5] Monreal 1992 [6] Nielsen, 1994 [7] Moreno-Cabral, 1976 [8] TOTAL
DVT = deep venous thrombosis, PE = pulmonary embolism, V/Q = ventilation/perfusion, Q = perfusion.
Silent PE n/N (%)
3/8 (37.5) 1/25 (4.0) 5/15 (33.3) 5/27 (18.5) 24/183 (13.1)
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Fig. 2. CT pulmonary angiogram, coronal view, same patient as Fig. 1. Pulmonary embolism on left is shown (arrow).
for silent PE as well. Recurrent PE in patients with DVT and silent PE was more frequent than an occurrence of PE in patients with DVT who did not have silent PE, 9 of 258 (3.5%) versus 4 of 742 (0.5%) (odds ratio 6.5) [17]. Others showed that DVT patients with silent PE at baseline had an increased incidence of PE events during the first 15 days of anticoagulant therapy, 8 of 822 (0.97%) versus 3 of 1496 (0.20%) (odds ratio 4.80 [14]. In view of such observations, Murin et al stated that DVT and PE appear to be distinct albeit overlapping clinical entities with different natural histories [15]. Lung scans in patients with symptomatic DVT and no clinical suspicion of PE may be useful, since some patients with silent PE may develop symptoms while on heparin therapy [9]. Monreal et al showed that 6 of 200 patients with DVT and silent PE developed symptoms during 7-day follow-up, but no new perfusion defects were found on repeated lung scan [9]. Without baseline scintigraphy all of these patients would have been considered to have recurrent PE, and vena cava interruption could have been performed because of a perceived failure of anticoagulants [9]. Silent PE may lead to pulmonary hypertension. The prevalence of chronic thromboembolic pulmonary hypertension after treatment for symptomatic acute PE in recent years has been reported to be 3.8% - 5.4% [18,19]. Without treatment, the prevalence of chronic thromboembolic pulmonary hypertension in patients with silent PE would be higher, because of a failure to prevent recurrent pulmonary embolism.
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The strength of this investigation is that it summarizes all data that use modern diagnostic techniques for DVT and PE to determine the prevalence of silent PE in patients with DVT limited to the calf veins. The data obtained comprise the most information compiled on this subject. Some of us previously determined the prevalence of silent PE in patients with DVT [10]. Distal DVT was defined similarly (infrapopliteal) in our previous investigation, except in one study, distal DVT included the distal portion of the popliteal vein [20]. The prevalence of silent PE that we now show in patients with distal DVT, 13.1%, is nearly identical to the prevalence that we showed previously, 15 of 113 (13.3%), and we now have data on 62% more patients [10]. Limitations include an inability to determine the size of the silent PE and the relation of silent PE to age, associated illness or clinical features due to the small number of patients in individual investigations. Another limitation is heterogeneity of the methods used for detection of silent PE, including different criteria for interpretation of the ventilation/ perfusion lung scans [21,22]. Imaging for silent PE in patients with calf vein DVT can be obtained with low exposure to radiation in most patients by using perfusion scintigraphy without ventilation scintigraphy [23]. The effective dose of 99mTc-MAA (macro aggregated albumin) perfusion lung scan is 0.68-2.04 mSv [24]. A ventilation scan with 81Kr would add 0.0280.28 mSv [25] and a ventilation scan with 99m Tc-DTPA (diethylene triamine pentaacetic acid) would add 0.14-0.21 mSv [24]. The effective dose of radiation with pulmonary scintigraphy is less than with CT pulmonary angiography. The average effective dose for 4-16 detector CT is 5.4 mSv based on computed data [26]. A measured effective dose of 19.9 + 1.38 mSv with 64-detector CT has been reported [27]. Breast doses were decreased from 62 mGy to 33 mGy with bismuth shields, but the effect of increased noise on the ability to diagnosis PE was not assessed [28]. Perfusion scintigraphy alone in patients with a normal or nearly normal chest radiograph can provide diagnostic accuracy similar to CT pulmonary angiography and ventilation/perfusion scintigraphy [23]. Chest radiographs were normal or nearly normal in 72% of patients with suspected PE, allowing a diagnosis or exclusion of PE by a perfusion scan alone [23]. Most patients with DVT, therefore, could be evaluated for silent PE with a perfusion scan alone. Those with lung disease, however, would require computed tomographic (CT) pulmonary angiography. If perfusion lung scans are not immediately available on the emergency service, it would be reasonable to obtain the scan the next day. The costs of routine screening for silent PE in patients with isolated calf DVT are a consideration as well as exposure to ionizing radiation, to which most patients would be exposed with no benefit. On the other hand, those in whom silent PE is identified could be treated knowledgeably with anticoagulants, rather than being followed for proximal extension of the thrombus. Dangers of an incorrect diagnosis of failure of treatment would be eliminated with baseline imaging. In conclusion, silent PE in patients with DVT limited to the calf veins is not rare. Imaging at the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may be useful, but there is an economic cost and exposure to radiation.
Financial disclosure The authors have no financial or other potential conflicts of interest relative to the data in this manuscript.
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Fig. 3. CT pulmonary angiogram, coronal view, same patient as Fig. 1. Pulmonary embolism on right is shown (arrow).
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