Pulmonary embolism assessment of clinical probability and risk scores
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Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D. [1], The APEX Trial Investigators; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
The diagnosis of pulmonary embolism 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. These variables predict the pretest probability that aids in the immediate management of high-risk patients.
Assessment of Clinical Probability
Clinical Prediction Rules
A clinical prediction rule is a type of medical research study in which the researchers try to identify the best combination of signs, symptoms, and other findings to predict the probability of a specific disease or outcome.[2] Clinical prediction rules for PE include: the Wells score, the Geneva score and the PE rule-out criteria. Its noteworthy that the use of any clinical prediction rule is associated with reduction in recurrent thromboembolism.[3] These clinical prediction rules are used to identify patients who should be treated.
Supportive Trial Data
- 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 a 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 a pulmonary embolism. The majority of these patients demonstrated low to moderate clinical probability which required no further intervention.[1]
- prospective multicentre outcome study by Musset et al, demonstrated that with-holding anticoagulation treatment in patients with low or intermediate clinical probability was safe as long as there was a negative spiral CT and negative ultrasonagraphy. 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.[4][5]
Wells Score
The Wells score is a simple, commonly used clinical risk prediction tool to evaluate the need for further testing in patients suspected to have pulmonary embolism.[6][7][8][9]
| Variable | Wells Score[8] |
|---|---|
| Clinically suspected DVT (leg swelling, pain with palpation) | 3.0 |
| Alternative diagnosis is less likely than PE | 3.0 |
| Immobilization/surgery in previous four weeks | 1.5 |
| Previous history of DVT or PE | 1.5 |
| Tachycardia (heart rate more than 100 bpm) | 1.5 |
| Malignancy (treatment for within 6 months, palliative) | 1.0 |
| Hemoptysis | 1.0 |
Wells Criteria [8][9]
- The following scoring system is used to assess the possible risk to a patient.[10] It also shows if there is a need for further testing with D-dimer or CT scan:
- Score >6.0 - High probability (~59%).
- Score 2.0 to 6.0 - Moderate probability (~29%).
- Score <2.0 - Low probability (~15%).
- The modified extended version of the Wells score has been proposed.[11]
- Score > 4 - PE likely. Consider diagnostic imaging.
- Score 4 or less - PE unlikely. Consider D-dimer to rule out PE.
- A simplified Wells criteria has been proposed[15], according to which all the 7 risk variables (table) are assigned 1 point each. A score ≤ 1 is categorized as unlikely to be PE. This score needs further validation in prospective studies.
Geneva Score[16]
- The Geneva score is a clinical prediction rule used to determine the pre-test probability of pulmonary embolism based on the patient's risk factors and clinical findings.
- The Geneva score has shown to be as accurate as the Wells score, but it is less reliant on the physicians clinical judgement.[17]
- The Geneva score has been revised and simplified from its original version, but it has been shown to have the same diagnostic utility as the original score.[18]
Original Geneva Score
Variables:
The original Geneva score is calculated using 7 risk factors and clinical variables:
| Variable | Score |
|---|---|
| Age | |
| 60–79 years | 1.0 |
| 80+ years | 2.0 |
| Previous venous thromboembolism | |
| History of prior DVT or PE | 2.0 |
| Previous surgery | |
| Recent surgery within 4 weeks | 3.0 |
| Heart rate | |
| Heart rate >100 beats per minute | 1.0 |
| PaCO2 (partial pressure of CO2 in arterial blood) | |
| <35mmHg | 2.0 |
| 35-39mmHg | 1.0 |
| PaO2 (partial pressure of O2 in arterial blood) | |
| <49mmHg | 4.0 |
| 49-59mmHg | 3.0 |
| 60-71mmHg | 2.0 |
| 72-82mmHg | 1.0 |
| Chest X-ray findings | |
| Band atelectasis | 1.0 |
| Elevation of hemidiaphragm | 1.0 |
Interpretation:
The score obtained correlates to the probability of the patient suffering from pulmonary embolism (the lower the score, the lower the probability).
- Score < 5 points - low probability of PE.
- Score 5 to 8 points - moderate probability of PE.
- Score > 8 points - high probability of PE.
Revised Geneva Score
Recently in 2006, the revised Geneva score was introduced with a more standarized and simplified algorithm to help predict the probability that a patient has a pulmonary embolism.[19] This simplified scoring system has shown to be as effective as the Wells score.[20]
Variables:
The revised score uses 8 parameters, excluding the assessment of arterial blood gas sample for the diagnosis of PE.
| Variable | Score |
|---|---|
| Age 65 years or over | 1.0 |
| Previous history of DVT or PE | 3.0 |
| Surgery or fracture within 1 month | 2.0 |
| Active malignant condition | 2.0 |
| Unilateral lower limb pain | 3.0 |
| Haemoptysis | 2.0 |
| Heart rate 75 to 94 beats per minute | 3.0 |
| Heart rate 95 or more beats per minute | 5.0 |
| Pain on deep palpation of lower limb and unilateral edema | 4.0 |
Interpretation:
The score obtained correlates to the probability of a pulmonary embolism. The results are summarized below:
- Score 0 to 3 points - lower probability (8%).
- Score 4 to 10 points - intermediate probability (28%).
- Score 11 points or more - higher probability (74%).
Simplified Geneva Score[18]
A one point, simplified scoring system replaced the previously weighted scores for each parameter. This was done to reduce the likelihood of error when the score is used in clinical settings. The simplified Geneva score does not lead to a decrease in diagnostic utility when compared to the previous Geneva scores.
Variables:
| Variable | Score |
|---|---|
| Age >65 | 1.0 |
| Previous history of DVT or PE | 1.0 |
| Surgery or fracture within 1 month | 1.0 |
| Active malignancy | 1.0 |
| Unilateral lower limb pain | 1.0 |
| Hemoptysis | 1.0 |
| Pain on deep vein palpation of lower limb and unilateral edema | 1.0 |
| Heart rate 75 to 94 bpm | 1.0 |
| Heart rate greater than 94 bpm* | +1 |
| * Heart rates of 75 to 94 bpm receive 1 point, while heart rates higher than 94bpm receive a further point (i.e. 2 points in total) | |
Interpretation:
There is a decreased likelihood of developing a pulmonary embolism if the score is 2 or below.
PE Rule-Out Criteria (PERC)
- The Pulmonary Embolism Rule-out Criteria, or PERC rule, helps to evaluate patients in whom pulmonary embolism is suspected, but is unlikely.
- Unlike the Wells Score and Geneva score, which are clinical prediction rules intended to risk stratify patients with suspected PE, the PERC rule is designed to rule out the risk of PE in low-risk patients stratified clinically by the physicians; hence, to prevent unnecessary diagnostic testing in this patient population.[21]
- In 2008, Kline et al, demonstrated that the PERC rule had a sensitivity of 97.4%, specificity of 21.9% and a false negative rate of 1.0% when used as a diagnostic test. The study further concluded that among patients with low suspicion for PE, a negative PERC rule reduced the probability of VTE to below 2% and in about 20% of outpatients with suspected PE.[22] On the similar lines, among the low pretest probability population, Wolf et al, demonstrated that the use of PERC-approach had a high negative predictive value and sensitivity, but a low positive predictive value and specificity.[21] On the contrary, among patients with a higher prevalence of PE (>20%), the PERC based approach has shown to have significantly poor predictive value.[23]
| Variables |
|---|
| Age less than 50 years? |
| No hemoptysis? |
| No estrogen use? |
| No prior history of DVT or PE? |
| No unilateral leg swelling? |
| No surgery or trauma requiring hospitalization within the past four weeks? |
| Heart rate less than 100 bpm? |
| Oxyhemoglobin saturation ≥95 percent? |
Interpretation:
If the answer to every question above is yes, then a pulmonary embolism can be ruled out according to the PERC rule.
Summary of PE Clinical Probability based on Clinical Prediction Rules
| Clinical Prediction Rules | Clinical Probability of PE | ||
| Low (%) | Moderate (%) | High (%) | |
| Empirical[11][16][1] | 10 | 31 | 61 |
| Extended Wells Score[11][9][7] | 4 | 30 | 68 |
| Simplified Wells Score[11][8][24] | 15 | 29 | 59 |
| Original Geneva Score[16][24] | 11 | 38 | 79 |
| Revised Geneva Score[19] | 8 | 29 | 74 |
Based on pooled study data. Adapted from Recommendations of The PIOPED II Investigators.[25]
ESC 2008 Guideline Recommendations[26]
Exclusion Criteria for PE
| Diagnostic Criteria | Clinical Probability of PE | ||
| Low | Intermediate | High | |
| Normal pulmonary angiogram. | + | + | + |
| D-dimer: Negative result, highly sensitive assay. | + | + | - |
| D-dimer: Negative result, moderately sensitive assay. | + | - | - |
| V/Q Scan: Normal lung scan. | + | + | + |
| V/Q Scan: Non-diagnostic lung scana. | + | - | - |
| V/Q Scan: Non-diagnostic lung scana and negative proximal compression venous ultrasonography. | + | + | ± |
| Chest CT: Normal single-detector CT and negative proximal compression venous ultrasonography. | + | + | ± |
| Chest CT: Normal multi-detector CT alone. | + | + | ± |
Confirmation of PE
| Diagnostic Criteria | Clinical Probability of PE | ||
| Low | Intermediate | High | |
| Pulmonary angiogram showing PE. | + | + | + |
| High-probability V/Q Scan. | ± | + | + |
| Compression venous ultrasonography showing proximal DVT. | + | + | + |
| Chest CT: Single or multi-detector helical CT showing PE (at least segmental). | ± | + | + |
| Chest CT: Single or multi-detector helical CT showing sub-segmental PE. | ± | ± | ± |
alow or intermediate probability lung scan according to the PIOPED classification.
| + | Valid Criteria: No further testing required. |
| - | Invalid Criteria: Further testing necessary. |
| + | Controversial Criteria: Further testing to be considered. |
| “ |
Adapted from 2008 ESC guidelines on the diagnosis and management of acute pulmonary embolism. |
” |
ESC 2008 Guidelines for Suspected High-Risk PE (DO NOT EDIT)[26]
| Class I |
| "1. In high-risk PE, as indicated by the presence of shock or hypotension, emergency CT or bedside echocardiography (depending on availability and clinical circumstances) is recommended for diagnostic purposes. (Level of Evidence: C)" |
ESC 2008 Guidelines for Suspected Non-High-Risk PE (DO NOT EDIT)[26]
| Class I |
| " 1. In non-high-risk PE, basing the diagnostic strategy on clinical probability assessed either implicitly or using a validated prediction rule is recommended. (Level of Evidence: A)" |
| " 2. Plasma D-dimer measurement is recommended in emergency department patients to reduce the need for unnecessary imaging and irradiation, preferably using a highly sensitive assay. (Level of Evidence: A)" |
| " 3. The use of validated criteria for diagnosing PE is recommended. Validated criteria according to clinical probability of PE(low, intermediate or high) are detailed below. (Level of Evidence: B)" |
| Class III |
| "1. Systematic use of echocardiography for diagnosis in haemodynamically stable, normotensive patients is not recommended.(Level of Evidence: C)" |
| Class IIa |
| "1. Pulmonary angiography should be considered when there is discrepancy between clinical evaluation and results of non-invasive imaging tests. (Level of Evidence: C)" |
| Class IIb |
| "1. Lower limb compression venous ultrasonography (CUS) in search of DVT may be considered in selected patients with suspected PE to obviate the need for further imaging tests if the result is positive. (Level of Evidence: B)" |
ESC 2008 Guidelines for Suspected Non-High-Risk PE (DO NOT EDIT)[26]
Low Clinical Probability
| Class I |
| "1. Normal D-dimer level using either a highly or moderately sensitive assay excludes PE. (Level of Evidence: A)" |
| "2. Normal perfusion lung scintigraphy excludes PE. (Level of Evidence: A)" |
| "3. Negative Multi-slice Detector CT (MDCT) safely excludes PE. (Level of Evidence: A)" |
| "4. Negative Single-slice Detector CT (SDCT) only excludes PE when combined with negative proximal compression venous ultrasonography.(Level of Evidence: A)" |
| "5. Compression venous ultrasonography (CUS) showing a proximal DVT confirms PE. (Level of Evidence: B)" |
| "6. SDCT or MDCT showing a segmental or more proximal thrombus confirms PE. (Level of Evidence: A)" |
| Class IIa |
| "1. Non-diagnostic (low or intermediate probability) V/Q scan may exclude PE, (Level of Evidence: B) particularly when combined with negative proximal CUS (Class I,Level of Evidence: A)" |
| "2. If Compression venous ultrasonography shows only a distal DVT, further testing should be considered to confirm PE. (Level of Evidence: B)" |
| "3. Further testing should be considered to confirm PE if SDCT or MDCT shows only subsegmental clots. (Level of Evidence: B)" |
| Class IIb |
| "1. High-probability V/Q scan may confirm PE but further testing may be considered in selected patients to confirm PE. (Level of Evidence: B)" |
Intermediate Clinical Probability
| Class I |
| "1. Normal D-dimer level using a highly sensitive assay excludes PE. (Level of Evidence: A)" |
| "2. Normal perfusion lung scintigraphy excludes PE. (Level of Evidence: A) " |
| "3. In case of a non-diagnostic V/Q scan, further testing is recommended to exclude or confirm PE. (Level of Evidence: B)" |
| "4. Negative MDCT excludes PE. (Level of Evidence: A)" |
| "5. Negative SDCT only excludes PE when combined with negative proximal CUS.(Level of Evidence: A)" |
| "6. High-probability ventilation–perfusion lung scintigraphy confirms PE. (Level of Evidence: A)" |
| "7. Compression venous ultrasonography showing a proximal DVT confirms PE. (Level of Evidence: B)" |
| "8. SDCT or MDCT showing a segmental or more proximal thrombus confirms PE. (Level of Evidence: A)" |
| Class IIa |
| "1. Further testing should be considered if D-dimer level is normal when using a less sensitive assay. (Level of Evidence: B) " |
| "2. If compression venous ultrasonography shows only a distal DVT, further testing should be considered. (Level of Evidence: B)" |
| Class IIb |
| "1. Further testing may be considered in case of subsegmental clots to confirm PE. (Level of Evidence: B)" |
High Clinical Probability
| Class I |
| "1. High-probability ventilation–perfusion lung scintigraphy confirms PE. (Level of Evidence: A) " |
| "2. Compression venous ultrasonography showing a proximal DVT confirms PE. (Level of Evidence: B)" |
| "3. SDCT or MDCT showing a segmental or more proximal thrombus confirms PE.(Level of Evidence: A)" |
| Class III |
| "1. D-dimer measurement is not recommended in high clinical probability patients as a normal result does not safely exclude PE even when using a highly sensitive assay. (Level of Evidence: C)" |
| Class IIa |
|
"1. In patients with a negative CT, further tests should be considered in selected patients to exclude PE. (Level of Evidence: B) " |
| Class IIb |
| "1. If compression venous ultrasonography shows only a distal DVT, further testing should be considered. (Level of Evidence: B)" |
| "2. Further testing may be considered where there are subsegmental clots, to confirm PE. (Level of Evidence: B)" |
References
- ↑ 1.0 1.1 1.2 "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) - ↑ 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.
- ↑ 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) - ↑ 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) - ↑ 7.0 7.1 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 8.3 8.4 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 9.2 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.
- ↑ 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.
- ↑ 11.0 11.1 11.2 11.3 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.
- ↑ Geersing, G.-J. (2012-10-04). "Safe exclusion of pulmonary embolism using the Wells rule and qualitative D-dimer testing in primary care: prospective cohort study". BMJ. 345 (oct04 2): e6564–e6564. doi:10.1136/bmj.e6564. ISSN 1756-1833. Retrieved 2012-10-05. Unknown parameter
|coauthors=ignored (help) - ↑ van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW; et al. (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.
- ↑ Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, Lang E, Stiell I, Kovacs G, Dreyer J, Dennie C, Cartier Y, Barnes D, Burton E, Pleasance S, Skedgel C, O'Rouke K, Wells PS (2007). "Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial". JAMA. 298 (23): 2743–53. doi:10.1001/jama.298.23.2743. PMID 18165667.
- ↑ Gibson NS, Sohne M, Kruip MJ, Tick LW, Gerdes VE, Bossuyt PM; et al. (2008). "Further validation and simplification of the Wells clinical decision rule in pulmonary embolism". Thromb Haemost. 99 (1): 229–34. doi:10.1160/TH07-05-0321. PMID 18217159.
- ↑ 16.0 16.1 16.2 Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A (2001). "Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score". Arch. Intern. Med. 161 (1): 92–7. PMID 11146703. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ Iles S, Hodges AM, Darley JR, Frampton C, Epton M, Beckert LE, Town GI (2003). "Clinical experience and pre-test probability scores in the diagnosis of pulmonary embolism". QJM. 96 (3): 211–5. PMID 12615985. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ 18.0 18.1 Klok FA, Mos IC, Nijkeuter M, Righini M, Perrier A, Le Gal G, Huisman MV (2008). "Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism". Arch. Intern. Med. 168 (19): 2131–6. doi:10.1001/archinte.168.19.2131. PMID 18955643. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ 19.0 19.1 Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bounameaux H, Perrier A (2006). "Prediction of pulmonary embolism in the emergency department: the revised Geneva score". Ann. Intern. Med. 144 (3): 165–71. PMID 16461960. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Righini M, Le Gal G, Aujesky D, Roy PM, Sanchez O, Verschuren F, Rutschmann O, Nonent M, Cornuz J, Thys F, Le Manach CP, Revel MP, Poletti PA, Meyer G, Mottier D, Perneger T, Bounameaux H, Perrier A (2008). "Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial". Lancet. 371 (9621): 1343–52. doi:10.1016/S0140-6736(08)60594-2. PMID 18424324. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ 21.0 21.1 Wolf SJ, McCubbin TR, Nordenholz KE, Naviaux NW, Haukoos JS (2008). "Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department". The American Journal of Emergency Medicine. 26 (2): 181–5. doi:10.1016/j.ajem.2007.04.026. PMID 18272098. Retrieved 2012-04-30. Unknown parameter
|month=ignored (help) - ↑ Kline JA, Courtney DM, Kabrhel C, Moore CL, Smithline HA, Plewa MC, Richman PB, O'Neil BJ, Nordenholz K (2008). "Prospective multicenter evaluation of the pulmonary embolism rule-out criteria". J. Thromb. Haemost. 6 (5): 772–80. doi:10.1111/j.1538-7836.2008.02944.x. PMID 18318689. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ Hugli O, Righini M, Le Gal G, Roy PM, Sanchez O, Verschuren F, Meyer G, Bounameaux H, Aujesky D (2011). "The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism". J. Thromb.Haemost. 9 (2): 300–4. doi:10.1111/j.1538-7836.2010.04147.x. PMID 21091866. Retrieved 2011-12-19. Unknown parameter
|month=ignored (help) - ↑ 24.0 24.1 Chagnon I, Bounameaux H, Aujesky D, Roy PM, Gourdier AL, Cornuz J, Perneger T, Perrier A (2002). "Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism". The American Journal of Medicine. 113 (4): 269–75. PMID 12361811. Retrieved 2012-04-30. Unknown parameter
|month=ignored (help) - ↑ {{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=[[The American Journal of Medicine|The American Journal of Medicine]] |volume=119 |issue=12 |pages=1048–55 |year=2006 |month=December |pmid=17145249 |doi=10.1016/j.amjmed.2006.05.060 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(06)00779-0 |accessdate=2012-04-30}}
- ↑ 26.0 26.1 26.2 26.3 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP (2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)". Eur. Heart J. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870. Retrieved 2011-12-07. Unknown parameter
|month=ignored (help)