Pulmonary embolism assessment of clinical probability and risk scores: Difference between revisions
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*The '''''Prospective Investigation On Pulmonary Embolism Diagnosis (PIOPED) investigators''''' demonstrated that all patients with or without pulmonary embolism had [[Pulmonary embolism ventilation/perfusion scan|abnormal V/Q scans]] of high, intermediate, or low probability ''(sensitivity, 98%; specificity, 10%)''. Furthermore, of the 116 patients with high-probability [[Pulmonary embolism ventilation/perfusion scan|scans]] and definitive angiograms, only 88% had pulmonary embolism. On the contrary, only a minority of patients with pulmonary embolism demonstrated high-probability scans ''(sensitivity, 41%; specificity, 97%)''. Similarly, of the 322 patients with intermediate-probability scans and definitive angiograms, only 33% had pulmonary embolism. Despite these contrast findings, classification of patients based on clinical probability was fairly accurate and that with increasing clinical probability, an increase in PE prevalence was also observed. However, majority of these patients demonstrated low to moderate clinical probability which required no further intervention.<ref name="pmid2332918">{{cite journal |author= |title=Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators |journal=[[JAMA : the Journal of the American Medical Association]] |volume=263 |issue=20 |pages=2753–9 |year=1990 |pmid=2332918 |doi= |url= |accessdate=2012-04-26}}</ref> | *The '''''Prospective Investigation On Pulmonary Embolism Diagnosis (PIOPED) investigators''''' demonstrated that all patients with or without pulmonary embolism had [[Pulmonary embolism ventilation/perfusion scan|abnormal V/Q scans]] of high, intermediate, or low probability ''(sensitivity, 98%; specificity, 10%)''. Furthermore, of the 116 patients with high-probability [[Pulmonary embolism ventilation/perfusion scan|scans]] and definitive angiograms, only 88% had pulmonary embolism. On the contrary, only a minority of patients with pulmonary embolism demonstrated high-probability scans ''(sensitivity, 41%; specificity, 97%)''. Similarly, of the 322 patients with intermediate-probability scans and definitive angiograms, only 33% had pulmonary embolism. Despite these contrast findings, classification of patients based on clinical probability was fairly accurate and that with increasing clinical probability, an increase in PE prevalence was also observed. However, majority of these patients demonstrated low to moderate clinical probability which required no further intervention.<ref name="pmid2332918">{{cite journal |author= |title=Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators |journal=[[JAMA : the Journal of the American Medical Association]] |volume=263 |issue=20 |pages=2753–9 |year=1990 |pmid=2332918 |doi= |url= |accessdate=2012-04-26}}</ref> | ||
*Another '''''prospective multicentre outcome study by Musset et al''''', demonstrated that with-holding anticoagulation in patients with low or intermediate clinical probability and negative spiral CT and ultrasonagraphy was safe. Of the 1041 patients enrolled in the study, 525 were assessed as having low or intermediate clinical probability and 507 were not treated with anticoagulation. During a 3-month follow-up, only 9 patients experienced [[venous thromboembolism]] ''(1.8% [0.8-3.3])'' and the diagnostic strategy proved inconclusive in 95 ''(9.1%)'' patients.<ref name="pmid12493257">{{cite journal |author=Musset D, Parent F, Meyer G, Maître S, Girard P, Leroyer C, Revel MP, Carette MF, Laurent M, Charbonnier B, Laurent F, Mal H, Nonent M, Lancar R, Grenier P, Simonneau G |title=Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study |journal=[[Lancet]] |volume=360 |issue=9349 |pages=1914–20 |year=2002 |month=December |pmid=12493257 |doi=10.1016/S0140-6736(02)11914-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(02)11914-3 |accessdate=2012-04-26}}</ref> | *Another '''''prospective multicentre outcome study by Musset et al''''', demonstrated that with-holding anticoagulation in patients with low or intermediate clinical probability and negative spiral CT and ultrasonagraphy was safe. Of the 1041 patients enrolled in the study, 525 were assessed as having low or intermediate clinical probability and 507 were not treated with anticoagulation. During a 3-month follow-up, only 9 patients experienced [[venous thromboembolism]] ''(1.8% [0.8-3.3])'' and the diagnostic strategy proved inconclusive in 95 ''(9.1%)'' patients.<ref name="pmid12493257">{{cite journal |author=Musset D, Parent F, Meyer G, Maître S, Girard P, Leroyer C, Revel MP, Carette MF, Laurent M, Charbonnier B, Laurent F, Mal H, Nonent M, Lancar R, Grenier P, Simonneau G |title=Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study |journal=[[Lancet]] |volume=360 |issue=9349 |pages=1914–20 |year=2002 |month=December |pmid=12493257 |doi=10.1016/S0140-6736(02)11914-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(02)11914-3 |accessdate=2012-04-26}}</ref><ref name="pmid10695691">{{cite journal |author=Perrier A, Miron MJ, Desmarais S, de Moerloose P, Slosman D, Didier D, Unger PF, Junod A, Patenaude JV, Bounameaux H |title=Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: Is it a valid option in patients with normal results of lower-limb venous compression ultrasonography? |journal=[[Archives of Internal Medicine]] |volume=160 |issue=4 |pages=512–6 |year=2000 |month=February |pmid=10695691 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=10695691 |accessdate=2012-04-26}}</ref> | ||
== | ==Clinical Prediction Rules== | ||
Clinical prediction rule is a type of medical research study in which the researchers try to identify the best combination of [[medical sign]], [[symptoms]], and other findings to predict the probability of a specific disease or outcome.<ref name="pmid10872017">{{cite journal |author=McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS |title=Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group |journal=[[JAMA : the Journal of the American Medical Association]] |volume=284 |issue=1 |pages=79–84 |year=2000 |month=July |pmid=10872017 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=10872017 |accessdate=2012-04-26}}</ref> | |||
Clinical prediction rules for PE include: the Wells score, the revised Geneva score. Its noteworthy that the use of '''any rule''' is associated with reduction in recurrent thromboembolism.<ref name="pmid16461959">{{cite journal |author=Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A |title=Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism |journal=Ann. Intern. Med. |volume=144 |issue=3 |pages=157-64 |year=2006 |pmid=16461959}}</ref> | |||
The most commonly used method to predict clinical probability is the Wells score | |||
===Wells Score=== | |||
=====Development of the Wells score===== | |||
The most commonly used method to predict clinical probability is the Wells score. | |||
In 1995, based on literature search and clinical criteria, Wells et al developed a [[clinical prediction rule|prediction rule]] to predict the likelihood of pulmonary embolism.<ref name="pmid7752753">{{cite journal |author=Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, Prandoni P |title=Accuracy of clinical assessment of deep-vein thrombosis |journal=[[Lancet]] |volume=345 |issue=8961 |pages=1326–30 |year=1995 |month=May |pmid=7752753 |doi= |url= |accessdate=2012-04-26}}</ref> The prediction rule was revised initially 1998<ref name="pmid9867786">{{cite journal |author=Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J |title=Use of a clinical model for safe management of patients with suspected pulmonary embolism |journal=Ann Intern Med |volume=129 |issue=12 |pages=997-1005 |year=1998 |pmid=9867786}}</ref> and a further revision in 2000.<ref name="pmid10744147">{{cite journal | author = Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, Turpie A, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J | title = Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. | journal = Thromb Haemost | volume = 83 | issue = 3 | pages = 416-20 | year = 2000 | id = PMID 10744147}}</ref> This year, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule. In 2001, Wells published the results using a more conservative cutoff of 2, to create three categories.<ref name="pmid11453709">{{cite journal |author=Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ |title=Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer |journal=Ann Intern Med |volume=135 |issue=2 |pages=98-107 |year=2001 |pmid=11453709 | url=http://www.annals.org/cgi/content/full/135/2/98}}</ref> | |||
*An additional version, the '''''modified extended version''''', using the more recent cutoff of 2 but including findings from Wells's initial studies were proposed.<ref name="pmid10739372">{{cite journal |author=Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Büller HR |title=Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group |journal=Thromb. Haemost. |volume=83 |issue=2 |pages=199-203 |year=2000 |pmid=10739372}}</ref> | |||
*Most recently, a further study reverted to Wells's earlier use of a cutoff of 4 points to create only two categories.<ref name="pmid16403929">{{cite journal |author=van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L |title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography |journal=JAMA |volume=295 |issue=2 |pages=172-9 |year=2006 |pmid=16403929 | url=http://jama.ama-assn.org/cgi/content/full/295/2/172 | doi=10.1001/jama.295.2.172}}</ref> | *Most recently, a further study reverted to Wells's earlier use of a cutoff of 4 points to create only two categories.<ref name="pmid16403929">{{cite journal |author=van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L |title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography |journal=JAMA |volume=295 |issue=2 |pages=172-9 |year=2006 |pmid=16403929 | url=http://jama.ama-assn.org/cgi/content/full/295/2/172 | doi=10.1001/jama.295.2.172}}</ref> | ||
=== | ====Wells score<ref name="pmid12952389">{{cite journal |author=Neff MJ |title=ACEP releases clinical policy on evaluation and management of pulmonary embolism |journal=American family physician |volume=68 |issue=4 |pages=759-60 |year=2003 |pmid=12952389 |doi=|url=http://www.aafp.org/afp/20030815/practice.html}}</ref> ==== | ||
=====Variables:===== | |||
*Clinically suspected [[DVT]] | *Immobilization/surgery in previous four weeks - 1.5 points | ||
*History of [[DVT]] or [[PE]] - 1.5 points | |||
*[[Malignancy]] (treatment for within 6 months, palliative) - 1.0 points | |||
*[[Hemoptysis]] - 1.0 points | |||
*[[Tachycardia]] - 1.5 points | |||
*Clinically suspected [[DVT]] (leg swelling, pain with palpation) - 3.0 points | |||
*Alternative diagnosis is less likely than PE - 3.0 points | *Alternative diagnosis is less likely than PE - 3.0 points | ||
=====Traditional interpretation (Wells criteria) <ref name="pmid10744147"/><ref name="pmid11453709"/>===== | |||
Traditional interpretation (Wells criteria) <ref name="pmid10744147"/><ref name="pmid11453709"/> | |||
* Score >6.0 - High (probability 59% based on pooled data<ref name="pmid17185658">{{cite journal |author=Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD |title=Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators |journal=Radiology |volume=242 |issue=1 |pages=15-21 |year=2007 |doi=10.1148/radiol.2421060971 | pmid=17185658}}</ref>) | * Score >6.0 - High (probability 59% based on pooled data<ref name="pmid17185658">{{cite journal |author=Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD |title=Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators |journal=Radiology |volume=242 |issue=1 |pages=15-21 |year=2007 |doi=10.1148/radiol.2421060971 | pmid=17185658}}</ref>) | ||
* Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data<ref name="pmid17185658"/>) | * Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data<ref name="pmid17185658"/>) | ||
* Score <2.0 - Low (probability 15% based on pooled data<ref name="pmid17185658"/>) | * Score <2.0 - Low (probability 15% based on pooled data<ref name="pmid17185658"/>) | ||
Alternate interpretation (Modified Wells criteria) <ref name="pmid10744147"/><ref name="pmid16403929"/> | =====Alternate interpretation (Modified Wells criteria) <ref name="pmid10744147"/><ref name="pmid16403929"/>===== | ||
* Score > 4 - PE likely. Consider diagnostic imaging. | * Score > 4 - PE likely. Consider diagnostic imaging. | ||
* Score 4 or less - PE unlikely. Consider [[D-dimer]] to rule out PE. | * Score 4 or less - PE unlikely. Consider [[D-dimer]] to rule out PE. |
Revision as of 19:22, 26 April 2012
Pulmonary Embolism Microchapters |
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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
The diagnosis of pulmonary embolism is based on clinical evaluation in conjunction with imaging modalities. Despite their individual sensitivities and specificities, studies have demonstrated that a combination of both these variables may help to discriminate suspected patients depending on their risk of developing pulmonary embolism and offer immediate management which is life-saving.
Pretest Probability
The diagnosis of PE is based primarily on the clinical evaluation combined with diagnostic modalities such as spiral CT, V/Q scan, use of the D-dimer and lower extremity ultrasound.
Although, the clinical pretest probability has shown to be fairly accurate,[1] the lack of validation has led to the use of a combination of both: clinical and diagnostic variables to predict the pretest probability that aids in the immediate management of high-risk patients.
High Pretest Probability
Many authors, reserve the term high pretest probability for those patients with a clinical presentation consistent with PE, in whom an alternative diagnosis is not apparent (e.g. pneumonia) and who have known risk factors for venous thromboembolism (VTE).
Low Pretest Probability
Low pretest probability patients include those patients with an alternative diagnosis to explain the clinical findings or those without risk factors.
Intermediate Pretest Probability
Intermediate probability patients include those patients not fitting either high or low pretest probability definitions.
Supportive trial data
- The Prospective Investigation On Pulmonary Embolism Diagnosis (PIOPED) investigators demonstrated that all patients with or without pulmonary embolism had abnormal V/Q scans of high, intermediate, or low probability (sensitivity, 98%; specificity, 10%). Furthermore, of the 116 patients with high-probability scans and definitive angiograms, only 88% had pulmonary embolism. On the contrary, only a minority of patients with pulmonary embolism demonstrated high-probability scans (sensitivity, 41%; specificity, 97%). Similarly, of the 322 patients with intermediate-probability scans and definitive angiograms, only 33% had pulmonary embolism. Despite these contrast findings, classification of patients based on clinical probability was fairly accurate and that with increasing clinical probability, an increase in PE prevalence was also observed. However, majority of these patients demonstrated low to moderate clinical probability which required no further intervention.[1]
- Another prospective multicentre outcome study by Musset et al, demonstrated that with-holding anticoagulation in patients with low or intermediate clinical probability and negative spiral CT and ultrasonagraphy was safe. Of the 1041 patients enrolled in the study, 525 were assessed as having low or intermediate clinical probability and 507 were not treated with anticoagulation. During a 3-month follow-up, only 9 patients experienced venous thromboembolism (1.8% [0.8-3.3]) and the diagnostic strategy proved inconclusive in 95 (9.1%) patients.[2][3]
Clinical Prediction Rules
Clinical prediction rule is a type of medical research study in which the researchers try to identify the best combination of medical sign, symptoms, and other findings to predict the probability of a specific disease or outcome.[4]
Clinical prediction rules for PE include: the Wells score, the revised Geneva score. Its noteworthy that the use of any rule is associated with reduction in recurrent thromboembolism.[5]
Wells Score
Development of the Wells score
The most commonly used method to predict clinical probability is the Wells score.
In 1995, based on literature search and clinical criteria, Wells et al developed a prediction rule to predict the likelihood of pulmonary embolism.[6] The prediction rule was revised initially 1998[7] and a further revision in 2000.[8] This year, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule. In 2001, Wells published the results using a more conservative cutoff of 2, to create three categories.[9]
- An additional version, the modified extended version, using the more recent cutoff of 2 but including findings from Wells's initial studies were proposed.[10]
- Most recently, a further study reverted to Wells's earlier use of a cutoff of 4 points to create only two categories.[11]
Wells score[12]
Variables:
- Immobilization/surgery in previous four weeks - 1.5 points
- History of DVT or PE - 1.5 points
- Malignancy (treatment for within 6 months, palliative) - 1.0 points
- Hemoptysis - 1.0 points
- Tachycardia - 1.5 points
- Clinically suspected DVT (leg swelling, pain with palpation) - 3.0 points
- Alternative diagnosis is less likely than PE - 3.0 points
Traditional interpretation (Wells criteria) [8][9]
- Score >6.0 - High (probability 59% based on pooled data[13])
- Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data[13])
- Score <2.0 - Low (probability 15% based on pooled data[13])
Alternate interpretation (Modified Wells criteria) [8][11]
- Score > 4 - PE likely. Consider diagnostic imaging.
- Score 4 or less - PE unlikely. Consider D-dimer to rule out PE.
References
- ↑ 1.0 1.1 "Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators". JAMA : the Journal of the American Medical Association. 263 (20): 2753–9. 1990. PMID 2332918.
|access-date=
requires|url=
(help) - ↑ Musset D, Parent F, Meyer G, Maître S, Girard P, Leroyer C, Revel MP, Carette MF, Laurent M, Charbonnier B, Laurent F, Mal H, Nonent M, Lancar R, Grenier P, Simonneau G (2002). "Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study". Lancet. 360 (9349): 1914–20. doi:10.1016/S0140-6736(02)11914-3. PMID 12493257. Retrieved 2012-04-26. Unknown parameter
|month=
ignored (help) - ↑ Perrier A, Miron MJ, Desmarais S, de Moerloose P, Slosman D, Didier D, Unger PF, Junod A, Patenaude JV, Bounameaux H (2000). "Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: Is it a valid option in patients with normal results of lower-limb venous compression ultrasonography?". Archives of Internal Medicine. 160 (4): 512–6. PMID 10695691. Retrieved 2012-04-26. Unknown parameter
|month=
ignored (help) - ↑ McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS (2000). "Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group". JAMA : the Journal of the American Medical Association. 284 (1): 79–84. PMID 10872017. Retrieved 2012-04-26. Unknown parameter
|month=
ignored (help) - ↑ Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A (2006). "Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism". Ann. Intern. Med. 144 (3): 157–64. PMID 16461959.
- ↑ Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, Prandoni P (1995). "Accuracy of clinical assessment of deep-vein thrombosis". Lancet. 345 (8961): 1326–30. PMID 7752753. Unknown parameter
|month=
ignored (help);|access-date=
requires|url=
(help) - ↑ Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (1998). "Use of a clinical model for safe management of patients with suspected pulmonary embolism". Ann Intern Med. 129 (12): 997–1005. PMID 9867786.
- ↑ 8.0 8.1 8.2 Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, Turpie A, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (2000). "Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer". Thromb Haemost. 83 (3): 416–20. PMID 10744147.
- ↑ 9.0 9.1 Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ (2001). "Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer". Ann Intern Med. 135 (2): 98–107. PMID 11453709.
- ↑ Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Büller HR (2000). "Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group". Thromb. Haemost. 83 (2): 199–203. PMID 10739372.
- ↑ 11.0 11.1 van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L (2006). "Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography". JAMA. 295 (2): 172–9. doi:10.1001/jama.295.2.172. PMID 16403929.
- ↑ Neff MJ (2003). "ACEP releases clinical policy on evaluation and management of pulmonary embolism". American family physician. 68 (4): 759–60. PMID 12952389.
- ↑ 13.0 13.1 13.2 Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD (2007). "Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators". Radiology. 242 (1): 15–21. doi:10.1148/radiol.2421060971. PMID 17185658.