Pulmonary embolism: Difference between revisions
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'''Pulmonary embolism''' (PE) is form of [[embolism and thromboembolism]] in which a blockage of the [[pulmonary artery]] (or one of its branches), usually when a [[deep vein thrombosis]] (blood clot from a vein), becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.<ref name="pmid18322285">{{cite journal |author=Tapson VF |title=Acute pulmonary embolism |journal=N. Engl. J. Med. |volume=358 |issue=10 |pages=1037–52 |year=2008 |month=March |pmid=18322285 |doi=10.1056/NEJMra072753 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18322285&promo=ONFLNS19 |issn=}}</ref> This process is termed ''thromboembolism''. | '''Pulmonary embolism''' (PE) is form of [[embolism and thromboembolism]] in which a blockage of the [[pulmonary artery]] (or one of its branches), usually when a [[deep vein thrombosis]] (DVT; a blood clot from a vein), becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.<ref name="pmid18322285">{{cite journal |author=Tapson VF |title=Acute pulmonary embolism |journal=N. Engl. J. Med. |volume=358 |issue=10 |pages=1037–52 |year=2008 |month=March |pmid=18322285 |doi=10.1056/NEJMra072753 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18322285&promo=ONFLNS19 |issn=}}</ref> This process is termed ''thromboembolism''. | ||
{{TOC | {{TOC|right}} | ||
==Pathophysiology== | ==Pathophysiology== | ||
The development of thrombosis is classically due to a group of causes named [[Virchow's triad]] (alterations in blood flow, factors in the vessel wall and factors affecting the properties of the blood). Often, more than one risk factor is present. | The development of thrombosis is classically due to a group of causes named [[Virchow's triad]] (alterations in blood flow, factors in the vessel wall and factors affecting the properties of the blood). Often, more than one risk factor is present. | ||
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* ''Factors affecting the properties of the blood'' (procoagulant state): | * ''Factors affecting the properties of the blood'' (procoagulant state): | ||
** [[Estrogen]]-containing [[hormonal contraception]] | ** [[Estrogen]]-containing [[hormonal contraception]] | ||
** Genetic thrombophilia ([[factor V Leiden]], | ** Genetic thrombophilia ([[factor V Leiden]], [[protein C deficiency]], [[protein S deficiency]], [[antithrombin]] deficiency, [[hyperhomocysteinemia]] and [[plasminogen]]/[[fibrinolysis]] disorders). The role of [[prothrombin]] mutation G20210A, is unclear.<ref name="pmid19531787">{{cite journal |author=Segal JB, Brotman DJ, Necochea AJ, ''et al.'' |title=Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review |journal=JAMA |volume=301 |issue=23 |pages=2472–85 |year=2009 |month=June |pmid=19531787 |doi=10.1001/jama.2009.853 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19531787 |issn=}}</ref> | ||
** Acquired thrombophilia ([[antiphospholipid syndrome]], [[nephrotic syndrome]], [[paroxysmal nocturnal hemoglobinuria]]) | ** Acquired thrombophilia (malignancy, [[antiphospholipid syndrome]], [[nephrotic syndrome]], [[paroxysmal nocturnal hemoglobinuria]]) | ||
==Diagnosis== | ==Diagnosis== | ||
The diagnosis of PE is based primarily on validated clinical criteria combined with selective testing because the typical clinical presentation ([[shortness of breath]], [[chest pain]]) cannot be definitively differentiated from other causes of chest pain and shortness of breath.<ref name="pmid14657070">{{cite journal |author=Chunilal SD, Eikelboom JW, Attia J, ''et al'' |title=Does this patient have pulmonary embolism? |journal=JAMA |volume=290 |issue=21 |pages=2849–58 |year=2003 |pmid=14657070 |doi=10.1001/jama.290.21.2849 |issn=}}</ref> Patients can present with atypical syndromes such as unexplained exacerbations of chronic obstructive pulmonary disease.<ref name="pmid16549851">{{cite journal |author=Tillie-Leblond I, Marquette CH, Perez T, ''et al'' |title=Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors |journal=Ann. Intern. Med. |volume=144 |issue=6 |pages=390–6 |year=2006 |month=March |pmid=16549851 |doi= |url= |issn=}}</ref> | The diagnosis of PE is based primarily on validated clinical criteria combined with selective testing because the typical clinical presentation ([[shortness of breath]], [[chest pain]]) cannot be definitively differentiated from other causes of chest pain and shortness of breath.<ref name="pmid14657070">{{cite journal |author=Chunilal SD, Eikelboom JW, Attia J, ''et al'' |title=Does this patient have pulmonary embolism? |journal=JAMA |volume=290 |issue=21 |pages=2849–58 |year=2003 |pmid=14657070 |doi=10.1001/jama.290.21.2849 |issn=}}</ref> Patients can present with atypical syndromes such as unexplained exacerbations of chronic obstructive pulmonary disease.<ref name="pmid16549851">{{cite journal |author=Tillie-Leblond I, Marquette CH, Perez T, ''et al'' |title=Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors |journal=Ann. Intern. Med. |volume=144 |issue=6 |pages=390–6 |year=2006 |month=March |pmid=16549851 |doi= |url= |issn=}}</ref> | ||
Regarding chest pain, the pain may be pleuritic.<ref name="pmid17904458">{{cite journal| author=Stein PD, Beemath A, Matta F, Weg JG, Yusen RD, Hales CA et al.| title=Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. | journal=Am J Med | year= 2007 | volume= 120 | issue= 10 | pages= 871-9 | pmid=17904458 | doi=10.1016/j.amjmed.2007.03.024 | pmc=PMC2071924 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17904458 }} (uncontrolled [[case series]])</ref><ref name="pmid3355304">{{cite journal| author=Hull RD, Raskob GE, Carter CJ, Coates G, Gill GJ, Sackett DL et al.| title=Pulmonary embolism in outpatients with pleuritic chest pain. | journal=Arch Intern Med | year= 1988 | volume= 148 | issue= 4 | pages= 838-44 | pmid=3355304 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3355304 }} </ref><ref name="pmid1909617">{{cite journal| author=Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson BT et al.| title=Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. | journal=Chest | year= 1991 | volume= 100 | issue= 3 | pages= 598-603 | pmid=1909617 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1909617 }} </ref> However, the reliability of assessing pleuritic may be low<ref name="pmid11823768">{{cite journal| author=Kline JA, Nelson RD, Jackson RE, Courtney DM| title=Criteria for the safe use of D-dimer testing in emergency department patients with suspected pulmonary embolism: a multicenter US study. | journal=Ann Emerg Med | year= 2002 | volume= 39 | issue= 2 | pages= 144-52 | pmid=11823768 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11823768 }} </ref> and a [[meta-analysis]] concludes that assessing pleuritic pain is not helpful.<ref name="pmid18089542">{{cite journal| author=West J, Goodacre S, Sampson F| title=The value of clinical features in the diagnosis of acute pulmonary embolism: systematic review and meta-analysis. | journal=QJM | year= 2007 | volume= 100 | issue= 12 | pages= 763-9 | pmid=18089542 | doi=10.1093/qjmed/hcm113 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18089542 }} </ref> | |||
[[D-dimer]] may be under-used in patients at low risk of pulmonary embolism.<ref name="pmid22664742">{{cite journal| author=Venkatesh AK, Kline JA, Courtney DM, Camargo CA, Plewa MC, Nordenholz KE et al.| title=Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure: Quantifying the Opportunity for ImprovementEvaluation of Pulmonary Embolism in ER. | journal=Arch Intern Med | year= 2012 | volume= | issue= | pages= 1-5 | pmid=22664742 | doi=10.1001/archinternmed.2012.1804 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22664742 }} </ref> Introduction of [[computed tomographic pulmonary angiography]] may have led to overdiagnosis of pulmonary embolism].<ref name="pmid21555660">{{cite journal| author=Wiener RS, Schwartz LM, Woloshin S| title=Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. | journal=Arch Intern Med | year= 2011 | volume= 171 | issue= 9 | pages= 831-7 | pmid=21555660 | doi=10.1001/archinternmed.2011.178 | pmc=PMC3140219 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21555660 }} </ref> | |||
===Probability scoring=== | ===Probability scoring=== | ||
Various clinical prediction | Various [[clinical prediction rule]]s exist to help diagnose PE, such as the Wells score and the [[Geneva rule]]. More importantly, the use of ''any'' rule may exclude PE when combined with a normal [[d-dimer]]<ref name="pmid21646554">{{cite journal| author=Douma RA, Mos IC, Erkens PM, Nizet TA, Durian MF, Hovens MM et al.| title=Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. | journal=Ann Intern Med | year= 2011 | volume= 154 | issue= 11 | pages= 709-18 | pmid=21646554 | doi=10.1059/0003-4819-154-11-201106070-00002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21646554 }} </ref> and use of ''any'' rule might be 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|url=http://www.annals.org/cgi/content/full/144/3/157}}</ref> | ||
====Wells score==== | ====Wells score==== | ||
;History of the Wells score | ;History of the Wells score | ||
The most commonly used method to predict clinical probability, the [[Wells score]], is a [[clinical prediction rule]], whose use is complicated by multiple versions being available. In | The most commonly used method to predict clinical probability, the [[Wells score]], is a [[clinical prediction rule]], whose use is complicated by multiple versions being available. In 1995, Wells ''et al'' initially developed a prediction rule (based on a literature search) to predict the likelihood of PE, based on clinical criteria.<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 |pmid=7752753 |doi=doi:10.1016/S0140-6736(95)92535-X}}</ref> The prediction rule was revised in 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> This prediction rule was further revised when simplified during a validation by Wells ''et al'' 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> In the 2000 publication, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule.<ref name="pmid10744147"/> In 2001, Wells published results using the 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<ref name="pmid7752753"/><ref name="pmid9867786"/> 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, studies (including one by Wells<ref name="pmid18165667">{{cite journal |author=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 |title=Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial |journal=JAMA |volume=298 |issue=23 |pages=2743-53 |year=2007 |pmid=18165667 |doi=10.1001/jama.298.23.2743 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18165667 |issn=}}</ref>) reverted to Wells's earlier use of a cutoff of ≤ 4 points<ref name="pmid10744147"/> 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><ref name="pmid18165667">{{cite journal |author=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 |title=Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial |journal=JAMA |volume=298 |issue=23 |pages=2743-53 |year=2007 |pmid=18165667 |doi=10.1001/jama.298.23.2743 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18165667 |issn=}}</ref> | ||
;Wells score | ;Wells score | ||
''The 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> | ''The 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> | ||
*clinically suspected | *clinically suspected DVT - 3.0 points | ||
*alternative diagnosis is less likely than PE - 3.0 points | *alternative diagnosis is less likely than PE - 3.0 points | ||
*tachycardia (>100 bpm) - 1.5 points | *tachycardia (>100 bpm) - 1.5 points | ||
Line 37: | Line 42: | ||
* Score <2.0 - Low (probability 4% to 15% based on pooled data<ref name="pmid17185658"/>) | * Score <2.0 - Low (probability 4% to 15% based on pooled data<ref name="pmid17185658"/>) | ||
Alternate interpretation<ref name="pmid10744147"/><ref name="pmid16403929"/><ref name="pmid18165667"/> | Alternate interpretation<ref>{{Cite journal | doi = 10.1136/bmj.e6564 | issn = 1756-1833 | volume = 345 | issue = oct04 2 | pages = e6564-e6564 | last = Geersing | first = G.-J. | coauthors = P. M. G. Erkens, W. A. M. Lucassen, H. R. Buller, H. t. Cate, A. W. Hoes, K. G. M. Moons, M. H. Prins, R. Oudega, H. C. P. M. van Weert, H. E. J. H. Stoffers | title = Safe exclusion of pulmonary embolism using the Wells rule and qualitative D-dimer testing in primary care: prospective cohort study | journal = BMJ | ||
| accessdate = 2012-10-05 | date = 2012-10-04 | url = http://www.bmj.com/content/345/bmj.e6564?etoc= | |||
}}</ref><ref name="pmid10744147"/><ref name="pmid16403929"/><ref name="pmid18165667"/> | |||
* 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. | ||
====Geneva score==== | ====Geneva score==== | ||
The Geneva score also has several versions including the original version with 7 items that include blood gas and chest radiograph<ref name="pmid11146703">{{cite journal |author=Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A |title=Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score |journal=Arch. Intern. Med. |volume=161 |issue=1 |pages=92–7 |year=2001 |month=January |pmid=11146703 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=11146703 |issn=}}</ref> the 'revised' version with 8 items using only [[sign (medical)|signs]] and [[symptom]]s <ref name="pmid16461960">{{cite journal |author=Le Gal G, Righini M, Roy PM, ''et al'' |title=Prediction of pulmonary embolism in the emergency department: the revised Geneva score |journal=Ann. Intern. Med. |volume=144 |issue=3 |pages=165–71 |year=2006 |month=February |pmid=16461960 |doi= |url=http://www.annals.org/cgi/content/full/144/3/165 |issn=}}</ref>, | The Geneva score also has several versions including the original version with 7 items that include blood gas and chest radiograph<ref name="pmid11146703">{{cite journal |author=Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A |title=Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score |journal=Arch. Intern. Med. |volume=161 |issue=1 |pages=92–7 |year=2001 |month=January |pmid=11146703 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=11146703 |issn=}}</ref> the 'revised' version with 8 items using only [[sign (medical)|signs]] and [[symptom]]s:<ref name="pmid16461960">{{cite journal |author=Le Gal G, Righini M, Roy PM, ''et al'' |title=Prediction of pulmonary embolism in the emergency department: the revised Geneva score |journal=Ann. Intern. Med. |volume=144 |issue=3 |pages=165–71 |year=2006 |month=February |pmid=16461960 |doi= |url=http://www.annals.org/cgi/content/full/144/3/165 |issn=}}</ref> | ||
{| class="wikitable" | |||
|+ Revised Geneva Score | |||
! Factor!! Points | |||
|- | |||
| colspan="2" align="center"| Risk factor | |||
|- | |||
| Age > 65|| 1 | |||
|- | |||
| Previous PE or [[Deep venous thrombosis|DVT]] || 3 | |||
|- | |||
| Surgery under general anesthesia or lower-limb fracture within 1 month|| 2 | |||
|- | |||
| Malignancy (either active or considered cured within 1 year|| 2 | |||
|- | |||
| colspan="2" align="center"| [[Symptom]]s | |||
|- | |||
| Unilateral lower-limb pain|| 3 | |||
|- | |||
| Hemoptysis|| 2 | |||
|- | |||
| colspan="2" align="center"| [[Sign (medical)|Clinical sign]]s | |||
|- | |||
| Heart rate 75-94|| 3 | |||
|- | |||
| Heart rate > 94|| 5 | |||
|- | |||
| Pain on lower-limb palpation and unilateral edema|| 4 | |||
|} | |||
{| class="wikitable" align="right" | |||
|+ Interpretation of the Revised Geneva Score | |||
! Points!! Clinical probability !!Prevalence of PE | |||
|- | |||
| 0 -3 || Low || 8% | |||
|- | |||
| 4 - 10|| Intermediate || 29% | |||
|- | |||
| > 10|| High || 74% | |||
|} | |||
More recently, a "'''Simplified revised version'''" assigns only one point to each [[sign (medical)|sign]] and [[symptom]]. The simplified version, which gives one point to each of the following:<ref name="pmid18955643">{{cite journal |author=Klok FA, Mos IC, Nijkeuter M, ''et al'' |title=Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism |journal=Arch. Intern. Med. |volume=168 |issue=19 |pages=2131–6 |year=2008 |month=October |pmid=18955643 |doi=10.1001/archinte.168.19.2131 |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=18955643 |issn=}}</ref> | |||
* age over 65 | * age over 65 | ||
* history of deep venous thrombosis or pulmonary embolism | * history of deep venous thrombosis or pulmonary embolism | ||
Line 52: | Line 101: | ||
* pain on lower-limb palpation and unilateral edema | * pain on lower-limb palpation and unilateral edema | ||
In this version, a patient with a score of 2 or less is unlikely to have a pulmonary embolism during the next three months. | In this version, a patient with a score of 2 or less is unlikely to have a pulmonary embolism during the next three months. | ||
====PERC==== | |||
The Pulmonary Embolism Rule-out Criteria (PERC) may identify patients who are at such low risk that d-dimer testing is not needed in low (<15% prevalence)<ref name="pmid18318689">{{cite journal| author=Kline JA, Courtney DM, Kabrhel C, Moore CL, Smithline HA, Plewa MC et al.| title=Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. | journal=J Thromb Haemost | year= 2008 | volume= 6 | issue= 5 | pages= 772-80 | pmid=18318689 | doi=10.1111/j.1538-7836.2008.02944.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18318689 }} </ref><ref name="pmid18272098">{{cite journal| author=Wolf SJ, McCubbin TR, Nordenholz KE, Naviaux NW, Haukoos JS| title=Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department. | journal=Am J Emerg Med | year= 2008 | volume= 26 | issue= 2 | pages= 181-5 | pmid=18272098 | doi=10.1016/j.ajem.2007.04.026 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18272098 }} </ref>, but not medium (>20% prevalence)<ref name="pmid21091866">{{cite journal| author=Hugli O, Righini M, Le Gal G, Roy PM, Sanchez O, Verschuren F et al.| title=The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism. | journal=J Thromb Haemost | year= 2011 | volume= 9 | issue= 2 | pages= 300-4 | pmid=21091866 | doi=10.1111/j.1538-7836.2010.04147.x | pmc= | url= }} </ref>, risk populations. | |||
===Blood tests=== | ===Blood tests=== | ||
In low/moderate suspicion of PE, a normal [[D-dimer]] level (shown in a [[blood test]]) is enough to exclude the possibility of thrombotic PE.<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, ''et al'' |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=Ann. Intern. Med. |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url= |issn=}} [http://www.acpjc.org/Content/141/3/issue/ACPJC-2004-141-3-077.htm ACP Journal Club review]</ref><ref name="pmid17155963">{{cite journal |author=Di Nisio M, Squizzato A, Rutjes AW, Büller HR, Zwinderman AH, Bossuyt PM |title=Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review |journal=J. Thromb. Haemost. |volume=5 |issue=2 |pages=296–304 |year=2007 |month=February |pmid=17155963 |doi=10.1111/j.1538-7836.2006.02328.x |url=http://dx.doi.org/10.1111/j.1538-7836.2006.02328.x |issn=}}</ref> | In low/moderate suspicion of PE, a normal [[D-dimer]] level (shown in a [[blood test]]) is enough to exclude the possibility of thrombotic PE.<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, ''et al'' |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=Ann. Intern. Med. |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url=http://www.annals.org/cgi/content/full/140/8/589 |issn=}} [http://www.acpjc.org/Content/141/3/issue/ACPJC-2004-141-3-077.htm ACP Journal Club review]</ref><ref name="pmid17155963">{{cite journal |author=Di Nisio M, Squizzato A, Rutjes AW, Büller HR, Zwinderman AH, Bossuyt PM |title=Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review |journal=J. Thromb. Haemost. |volume=5 |issue=2 |pages=296–304 |year=2007 |month=February |pmid=17155963 |doi=10.1111/j.1538-7836.2006.02328.x |url=http://dx.doi.org/10.1111/j.1538-7836.2006.02328.x |issn=}}</ref><ref name="pmid19620439">{{cite journal |author=Gupta RT, Kakarla RK, Kirshenbaum KJ, Tapson VF |title=D-dimers and efficacy of clinical risk estimation algorithms: sensitivity in evaluation of acute pulmonary embolism |journal=AJR Am J Roentgenol |volume=193 |issue=2 |pages=425–30 |year=2009 |month=August |pmid=19620439 |doi=10.2214/AJR.08.2186 |url=http://www.ajronline.org/cgi/pmidlookup?view=long&pmid=19620439 |issn=}}</ref> Unfortunately, many or even most doctors do not explicitly calculate pretest probability when interpreting the results of the d-dimer.<ref name="pmid19000347">{{cite journal |author=Smith C, Mensah A, Mal S, Worster A |title=Is pretest probability assessment on emergency department patients with suspected venous thromboembolism documented before SimpliRED D-dimer testing? |journal=CJEM |volume=10 |issue=6 |pages=519–23 |year=2008 |month=November |pmid=19000347 |doi= |url=http://www.cjem-online.ca/v10/n6/p519 |issn=}}</ref> | ||
[[Immunologic test]]s for d-dimer are generally use [[immunoassay]]s such as [[enzyme-linked immunosorbent assay]] or [[serologic test]]s such as [[agglutination test]]s. The [[immunoassay]]s (more specifically, [[enzyme-linked immunosorbent assay]]) tend to be more [[sensitivity and specificity|sensitive]].<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, ''et al.'' |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=Ann. Intern. Med. |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url=http://www.annals.org/cgi/content/full/140/8/589 |issn=}}</ref> | |||
{| class="wikitable" align="right" | {| class="wikitable" align="right" | ||
|+ D-dimer tests<ref name="pmid15096330"/> | |+ D-dimer tests for pulmonary embolism<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, ''et al.'' |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=Ann. Intern. Med. |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url=http://www.annals.org/cgi/content/full/140/8/589 |issn=}}</ref><ref name="pmid17155963">{{cite journal |author=Di Nisio M, Squizzato A, Rutjes AW, Büller HR, Zwinderman AH, Bossuyt PM |title=Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review |journal=J. Thromb. Haemost. |volume=5 |issue=2 |pages=296–304 |year=2007 |month=February |pmid=17155963 |doi=10.1111/j.1538-7836.2007.02328.x |url=http://dx.doi.org/10.1111/j.1538-7836.2007.02328.x |issn=}}</ref> | ||
! !! [[sensitivity and specificity|sensitivity]]!! [[sensitivity and specificity|specificity]] | ! !! [[sensitivity and specificity|sensitivity]]!! [[sensitivity and specificity|specificity]] | ||
|- | |- | ||
| [[Enzyme-linked immunosorbent assay|Elisa]] | | colspan="3" align="center"|[[Immunoassay]]s | ||
|- | |||
| [[Enzyme-linked immunosorbent assay|Elisa]] such as VIDAS™|| 95%<ref name="pmid15096330"/><br>96%<ref name="pmid17155963"/>|| 44%<ref name="pmid15096330"/><br>39%<ref name="pmid17155963"/> | |||
|- | |- | ||
| | | colspan="3" align="center"|[[Agglutination test]]s | ||
|- | |- | ||
| Whole blood [[hemagglutination test]] | | [[Latex fixation test|Latex agglutination]] such as Tinaquant™||89%<ref name="pmid15096330"/><br>96%<ref name="pmid17155963"/>|| 45%<ref name="pmid15096330"/><br>43%<ref name="pmid17155963"/> | ||
|- | |||
| Whole blood [[hemagglutination test]] such as SimpliRED™|| 78%<ref name="pmid15096330"/><br>87%<ref name="pmid17155963"/>|| 74%<ref name="pmid15096330"/><br>66%<ref name="pmid17155963"/> | |||
|} | |} | ||
Line 77: | Line 135: | ||
;Role in diagnosis | ;Role in diagnosis | ||
Assessing the ''accuracy'' of CT pulmonary angiography is hindered by the rapid changes in the number of rows of detectors available in multidetector CT (MDCT) machines.<ref name="pmid16479644">{{cite journal |author=Schaefer-Prokop C, Prokop M |title=MDCT for the diagnosis of acute pulmonary embolism |journal=European radiology |volume=15 Suppl 4 |issue= |pages=D37-41 |year=2005 |pmid=16479644 |doi=}}</ref> The PIOPED II study used a mixture of 4 slice and 16 slice scanners and reported a [[sensitivity (tests)|sensitivity]] of 83% and a [[specificity (tests)|specificity]] of 96%. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging results.<ref name="pmid16738268">{{cite journal |author=Stein PD, Fowler SE, Goodman LR, | Assessing the ''accuracy'' of CT pulmonary angiography is hindered by the rapid changes in the number of rows of detectors available in multidetector CT (MDCT) machines.<ref name="pmid16479644">{{cite journal |author=Schaefer-Prokop C, Prokop M |title=MDCT for the diagnosis of acute pulmonary embolism |journal=European radiology |volume=15 Suppl 4 |issue= |pages=D37-41 |year=2005 |pmid=16479644 |doi=}}</ref> The PIOPED II study used a mixture of 4 slice and 16 slice scanners and reported a [[sensitivity (tests)|sensitivity]] of 83% and a [[specificity (tests)|specificity]] of 96%. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging results.<ref name="pmid16738268">{{cite journal| author=Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD et al.| title=Multidetector computed tomography for acute pulmonary embolism. | journal=N Engl J Med | year= 2006 | volume= 354 | issue= 22 | pages= 2317-27 | pmid=16738268 | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16738268 | doi=10.1056/NEJMoa052367 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17080988 Review in: ACP J Club. 2006 Nov-Dec;145(3):76] <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> | |||
{| class="wikitable" | |||
|+ Positive predictive value of CT pulmonary angiography (CTA) in the PIOPED II study<ref name="pmid16738268">{{cite journal| author=Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD et al.| title=Multidetector computed tomography for acute pulmonary embolism. | journal=N Engl J Med | year= 2006 | volume= 354 | issue= 22 | pages= 2317-27 | pmid=16738268 | |||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16738268 | doi=10.1056/NEJMoa052367 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17080988 Review in: ACP J Club. 2006 Nov-Dec;145(3):76] <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> | |||
! Location of embolism!! Number of patients <br/>with true positive CTA||Total number of patients <br/>with this finding on CTA!!Total number of patients <br/>with embolism in this location!![[Positive predictive value]] of CTA | |||
|- | |||
| Any||150||175||183||86% | |||
|- | |||
| Embolism in a main or lobar artery|| 116||120||Not reported||97% | |||
|- | |||
| Segmental vessel||32||47||Not reported||68% | |||
|- | |||
| Subsegmental branch|| 2||8||Not reported||25% | |||
|} | |||
;Role in Prognosis | ;Role in Prognosis | ||
Line 90: | Line 164: | ||
====Ventilation/perfusion scan==== | ====Ventilation/perfusion scan==== | ||
''[[Ventilation/perfusion scan]]'' (or ''V/Q scan'' or ''lung [[scintigraphy]]''), which shows that some areas of the lung are being [[Ventilation (physiology)|ventilated]] but not [[Perfusion|perfused]] with blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in patients who have an allergy to [[iodinated contrast]] or in [[pregnancy]] due to lower radiation exposure than CT. | ''[[Ventilation/perfusion scan]]'' (or ''V/Q scan'' or ''lung [[scintigraphy]]''), which shows that some areas of the lung are being [[Ventilation (physiology)|ventilated]] but not [[Perfusion|perfused]] with blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in patients who have an allergy to [[iodinated contrast]] or in [[pregnancy]] due to lower radiation exposure than CT. | ||
For patients with a normal [[chest x-ray]], doing a V/Q scan rather than [[computed tomographic pulmonary angiography]] may reduce radiation exposure.<ref name="pmid20093601">{{cite journal| author=Stein EG, Haramati LB, Chamarthy M, Sprayregen S, Davitt MM, Freeman LM| title=Success of a safe and simple algorithm to reduce use of CT pulmonary angiography in the emergency department. | journal=AJR Am J Roentgenol | year= 2010 | volume= 194 | issue= 2 | pages= 392-7 | pmid=20093601 | |||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=20093601 | doi=10.2214/AJR.09.2499 }}</ref> | |||
====Chest X-ray==== | ====Chest X-ray==== | ||
''[[Chest X-ray]]s'' are often done on patients with shortness of breath to help rule-out other causes, such as [[congestive heart failure]] and [[rib fracture]]. Chest X-rays in PE are rarely normal,<ref>{{cite journal | author = Worsley D, Alavi A, Aronchick J, Chen J, Greenspan R, Ravin C | title = Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study. | journal = Radiology | volume = 189 | issue = 1 | pages = 133-6 | year = 1993 | id = PMID 8372182}}</ref> but usually lack [[radiologic sign|sign]]s that suggest the diagnosis of PE (e.g. [[Westermark sign]], [[Hampton's hump]]). | ''[[Chest X-ray]]s'' are often done on patients with shortness of breath to help rule-out other causes, such as [[congestive heart failure]] and [[rib fracture]]. Chest X-rays in PE are rarely normal,<ref>{{cite journal | author = Worsley D, Alavi A, Aronchick J, Chen J, Greenspan R, Ravin C | title = Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study. | journal = Radiology | volume = 189 | issue = 1 | pages = 133-6 | year = 1993 | id = PMID 8372182}}</ref> but usually lack [[radiologic sign|sign]]s that suggest the diagnosis of PE (e.g. [[Westermark sign]], [[Hampton's hump]]). | ||
====Magnetic resonance imaging==== | |||
[[Magnetic resonance imaging]] with gadolinium has lower [[sensitivity and specificity|sensitivity]] than other methods and images are not always technically adequate.<ref name="pmid20368649">{{cite journal| author=Stein PD, Chenevert TL, Fowler SE, Goodman LR, Gottschalk A, Hales CA et al.| title=Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III). | journal=Ann Intern Med | year= 2010 | volume= 152 | issue= 7 | pages= 434-43, W142-3 | pmid=20368649 | |||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20368649 | doi=10.1059/0003-4819-152-7-201004060-00008 }} </ref> | |||
====Ultrasonography of the legs==== | ====Ultrasonography of the legs==== | ||
[[Ultrasonography]] or [[Duplex Doppler ultrasonography]] of the legs may help by diagnosing [[deep vein thrombosis]] (DVT) of the legs that may have led to pulmonary embolism. The presence of DVT, as shown on [[ultrasonography]] of the legs usually warrants [[anticoagulation]], because of the strong association between DVT and PE. | |||
Examining the legs may be valid approach in [[pregnancy]], in [[x-ray]]s might cause birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism. | |||
===Electrocardiogram findings=== | ===Electrocardiogram findings=== | ||
An [[electrocardiogram|ECG]] may show signs of right heart strain or acute ''[[cor pulmonale]]'' in cases of large PEs - the classic signs are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III ("S1Q3T3").<ref name="pmid18436792">{{cite journal |author=Miniati M, Bottai M, Monti S, Salvadori M, Serasini L, Passera M |title=Simple and accurate prediction of the clinical probability of pulmonary embolism |journal=Am. J. Respir. Crit. Care Med. |volume=178 |issue=3 |pages=290–4 |year=2008 |month=August |pmid=18436792 |doi=10.1164/rccm.200802-207OC |url=http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=18436792 |issn=}}</ref><ref>McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism. ''J Am Med Assoc'' 1935;104:1473–1480.</ref> This is occasionally (up to 20%) present, but may also occur in other acute lung conditions and has therefore limited diagnostic value; the most commonly seen sign in the ECG is sinus tachycardia. | |||
===Echocardiography findings=== | ===Echocardiography findings=== | ||
Line 106: | Line 189: | ||
===Combining tests into algorithms=== | ===Combining tests into algorithms=== | ||
Recent recommendations for a diagnostic algorithm have been published by the PIOPED II investigators; however, these recommendations do not reflect research using 64 slice MDCT.<ref name="pmid17185658"/> These investigators recommended: | Recent recommendations for a diagnostic algorithm have been published by the PIOPED II investigators; however, these recommendations do not reflect research using 64 slice MDCT.<ref name="pmid17145249">{{cite journal| author=Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD et al.| title=Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. | journal=Am J Med | year= 2006 | volume= 119 | issue= 12 | pages= 1048-55 | pmid=17145249 | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17145249 | doi=10.1016/j.amjmed.2006.05.060 }}</ref><ref name="pmid17185658"/> These investigators recommended: | |||
* Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer, obtain MDCT and based treatment on results. | * Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer, obtain MDCT and based treatment on results. | ||
* Moderate clinical probability. If negative D-dimer, PE is excluded. ''However'', the authors were not concerned that a negative MDCT with negative D-dimer in this setting has an 5% probability of being false. Presumably, the 5% error rate will fall as 64 slice MDCT is more commonly used. If positive D-dimer, obtain MDCT and based treatment on results. | * Moderate clinical probability. If negative D-dimer, PE is excluded. ''However'', the authors were not concerned that a negative MDCT with negative D-dimer in this setting has an 5% probability of being false. Presumably, the 5% error rate will fall as 64 slice MDCT is more commonly used. If positive D-dimer, obtain MDCT and based treatment on results. | ||
Line 112: | Line 196: | ||
==Treatment== | ==Treatment== | ||
In most cases, anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as [[oxygen therapy|oxygen]] or [[analgesia]], are often required. | In most cases, anticoagulant therapy is the mainstay of treatment. Some patients at risk of bleeding and with low risk of recurrent embolism may have treatment safely withheld.<ref name="pmid10996581">{{cite journal |author=Stein PD, Hull RD, Raskob GE |title=Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial noninvasive leg tests |journal=Am. J. Med. |volume=109 |issue=4 |pages=301–6 |year=2000 |month=September |pmid=10996581 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(00)00508-8 |issn=}}</ref> Acutely, supportive treatments, such as [[oxygen therapy|oxygen]] or [[analgesia]], are often required. See [[respiratory emergencies]] and [[critical care]]. | ||
===Anticoagulation=== | ===Anticoagulation=== | ||
{{main|anticoagulant}} | {{main|anticoagulant}} | ||
In most cases, [[anticoagulant]] therapy is the mainstay of treatment. [[Heparin]], [[low molecular weight heparin]]s (such as [[enoxaparin]] and [[dalteparin]]), or [[fondaparinux]] is administered initially, while [[warfarin]] therapy is commenced (this may take several days, usually while the patient is in hospital). Warfarin therapy often requires frequent dose adjustment and monitoring of the [[international normalized ratio|INR]]. In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. [[low molecular weight heparin]]. In patients with an underlying malignancy, therapy with a course of [[low molecular weight heparin]] may be favored over warfarin based on the results of the CLOT trial.<ref>{{cite journal | author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M | title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year=2003 | pages=146-53 | volume=349 | issue=2 | id=PMID 12853587}}</ref> Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known [[teratogenic]] effects of warfarin. | In most cases, [[anticoagulant]] therapy is the mainstay of treatment. [[Heparin]], [[low molecular weight heparin]]s (such as [[enoxaparin]] and [[dalteparin]]), or [[fondaparinux]] is administered initially, while [[warfarin]] therapy is commenced (this may take several days, usually while the patient is in hospital). Warfarin therapy often requires frequent dose adjustment and monitoring of the [[international normalized ratio|INR]]. In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. [[low molecular weight heparin]]. In patients with an underlying malignancy, therapy with a course of [[low molecular weight heparin]] may be favored over warfarin based on the results of the CLOT trial.<ref>{{cite journal | author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M | title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year=2003 | pages=146-53 | volume=349 | issue=2 | id=PMID 12853587}}</ref> Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known [[teratogenic]] effects of warfarin. | ||
Sometimes, anticoagulation may be done as an outpatient.<ref name="pmid15824291">{{cite journal |author=Wells PS, Anderson DR, Rodger MA, ''et al'' |title=A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism |journal=Arch. Intern. Med. |volume=165 |issue=7 |pages=733–8 |year=2005 |month=April |pmid=15824291 |doi=10.1001/archinte.165.7.733 |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=15824291 |issn=}}</ref><ref name="pmid10739374">{{cite journal |author=Kovacs MJ, Anderson D, Morrow B, Gray L, Touchie D, Wells PS |title=Outpatient treatment of pulmonary embolism with dalteparin |journal=Thromb. Haemost. |volume=83 |issue=2 |pages=209–11 |year=2000 |month=February |pmid=10739374 |doi= |url=http://www.schattauer.de/index.php?id=1268&pii=th00020209&no_cache=1 |issn=}}</ref><ref>Jiminez D, Yusen RD. Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy. Curr Opin Pulm Med. 2008 Sep;14(5):414-21. PMID 18664971</ref><ref>Janjua M, Badshah A, Matta F, Danescu LG, Yaekoub AY, Stein PD. Treatment of acute pulmonary embolism as outpatients or following early discharge. A systematic review. Thromb Haemost. 2008 Nov;100(5):756-61. PMID 18989517</ref> | |||
====Duration of treatment==== | ====Duration of treatment==== | ||
Regarding the duration of anticoagulation, see [[embolism and thrombosis#treatment|embolism and thrombosis: treatment]]. | Regarding the duration of anticoagulation, see [[embolism and thrombosis#treatment|embolism and thrombosis: treatment]]. | ||
=== | ===Vena cava filter=== | ||
If anticoagulant therapy is contraindicated and/or ineffective an [[ | If anticoagulant therapy is contraindicated and/or ineffective an inferior [[vena cava filter]] may be implanted<ref name="pmid9459643">{{cite journal |author=Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral F, Huet Y, Simonneau G |title=A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group |journal=N Engl J Med |volume=338 |issue=7 |pages=409-15 |year=1998 |id=PMID 9459643}}</ref>; however, the risk-benefit is uncertain.<ref name="pmid17943896">{{cite journal |author=Young T, Tang H, Aukes J, Hughes R |title=Vena caval filters for the prevention of pulmonary embolism |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD006212 |year=2007 |pmid=17943896 |doi=10.1002/14651858.CD006212.pub3}}</ref> | ||
A superior [[vena cava filter]] can be used for upper extremity thrombosis; however, the median survival is approximately one month.<ref name="pmid18809292">{{cite journal |author=Usoh F, Hingorani A, Ascher E, ''et al'' |title=Long-term Follow-up for Superior Vena Cava Filter Placement |journal=Ann Vasc Surg |volume= |issue= |pages= |year=2008 |month=September |pmid=18809292 |doi=10.1016/j.avsg.2008.08.012 |url=http://linkinghub.elsevier.com/retrieve/pii/S0890-5096(08)00313-0 |issn=}}</ref><ref name="pmid11054219">{{cite journal |author=Ascher E, Hingorani A, Tsemekhin B, Yorkovich W, Gunduz Y |title=Lessons learned from a 6-year clinical experience with superior vena cava Greenfield filters |journal=J. Vasc. Surg. |volume=32 |issue=5 |pages=881–7 |year=2000 |month=November |pmid=11054219 |doi=10.1067/mva.2000.110883 |url=http://linkinghub.elsevier.com/retrieve/pii/S0741-5214(00)74115-2 |issn=}}</ref> A retrievable filter has been used.<ref name="pmid12357312">{{cite journal |author=Nadkarni S, Macdonald S, Cleveland TJ, Gaines PA |title=Placement of a retrievable Günther Tulip filter in the superior vena cava for upper extremity deep venous thrombosis |journal=Cardiovasc Intervent Radiol |volume=25 |issue=6 |pages=524–6 |year=2002 |pmid=12357312 |doi=10.1007/s00270-001-0112-9 |url=http://dx.doi.org/10.1007/s00270-001-0112-9 |issn=}}</ref> | |||
===Thrombolysis=== | ===Thrombolysis=== | ||
{{main|Thrombolysis}} | {{main|Thrombolysis}} | ||
[[Clinical practice guideline]]s address the management of severe forms of [[embolism and thrombosis]] which may require [[thrombolysis]].<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association. | journal=Circulation | year= 2011 | volume= | issue= | pages= | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387 }} </ref> An algorithm from the guidelines is online at http://circ.ahajournals.org/content/123/16/1788/F2.large.jpg. Massive PE causing hemodynamic instability (marked decreased [[oxygen saturation]], [[tachycardia]] and/or [[hypotension]]) is an indication for [[thrombolysis]], the enzymatic destruction of the clot with medication. | |||
For submassive PE, some advocate thrombolysis if right ventricular dysfunction can be demonstrated on [[echocardiography]].<ref>Goldhaber SZ. Pulmonary embolism. ''[[The Lancet|Lancet]]'' 2004;363:1295-305. PMID 15094276.</ref> However, an uncontrolled study suggests that submassive saddle PEs may not require thrombolysis.<ref name="pmid21705903">{{cite journal| author=Sardi A, Gluskin J, Guttentag A, Kotler MN, Braitman LE, Lippmann M| title=Saddle pulmonary embolism: Is it as bad as it looks? A community hospital experience. | journal=Crit Care Med | year= 2011 | volume= 39 | issue= 11 | pages= 2413-8 | pmid=21705903 | doi=10.1097/CCM.0b013e31822571b2 | pmc= | url= }} </ref> | |||
[[Thrombolysis]] can be given for severe PEs when surgery is not immediately available or possible (e.g. periarrest or during cardiac arrest). The only trial that addressed this issue had 8 patients; the four receiving thrombolysis survived, while the four who received only heparin died.<ref>Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M, Arriaga-Nava R, Valencia S, Rosado-Buzzo A, Pierzo JA, Rosas E. Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism: A Randomized Controlled Trial. ''J Thromb Thrombolysis'' 1995;2:227-229. PMID 10608028.</ref> The use of thrombolysis in moderate PEs is still debatable. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or [[cerebrovascular accident|stroke]].<ref>Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. ''Cochrane Database Syst Rev'' 2006;(2):CD004437. PMID 16625603.</ref> | [[Thrombolysis]] can be given for severe PEs when surgery is not immediately available or possible (e.g. periarrest or during cardiac arrest). The only trial that addressed this issue had 8 patients; the four receiving thrombolysis survived, while the four who received only heparin died.<ref>Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M, Arriaga-Nava R, Valencia S, Rosado-Buzzo A, Pierzo JA, Rosas E. Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism: A Randomized Controlled Trial. ''J Thromb Thrombolysis'' 1995;2:227-229. PMID 10608028.</ref> The use of thrombolysis in moderate PEs is still debatable. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or [[cerebrovascular accident|stroke]].<ref>Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. ''Cochrane Database Syst Rev'' 2006;(2):CD004437. PMID 16625603.</ref> | ||
Line 136: | Line 226: | ||
==Prognosis== | ==Prognosis== | ||
Mortality from untreated PE is said to be 26%. | Mortality from untreated PE is said to be 26% based on the outcome in patients who received placebo treatment.<ref name="pmid13797091">{{cite journal |author=Barritt DW, Jordan SC | title=Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. | journal=Lancet | year=1960 | volume=1 | pages=1309-1312 | pmid=13797091 }}</ref> The rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs. | ||
With treatment, emboli resolve.<ref name="pmid20410413">{{cite journal| author=Stein PD, Yaekoub AY, Matta F, Janjua M, Patel RM, Goodman LR et al.| title=Resolution of pulmonary embolism on CT pulmonary angiography. | journal=AJR Am J Roentgenol | year= 2010 | volume= 194 | issue= 5 | pages= 1263-8 | pmid=20410413 | |||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20410413 | doi=10.2214/AJR.09.3410 }} </ref> About half of emboli cannot be imaged after 10 days and about 80% cannot be imaged after one month.<ref name="pmid20410413"/> | |||
===Predicting | Prognosis depends on the amount of lung that is affected (embolic burden)<ref name="pmid22628491">{{cite journal| author=Vedovati MC, Becattini C, Agnelli G, Kamphuisen PW, Masotti L, Pruszczyk P et al.| title=MULTIDETECTOR COMPUTED TOMOGRAPHY FOR ACUTE PULMONARY EMBOLISM: EMBOLIC BURDEN AND CLINICAL OUTCOME. | journal=Chest | year= 2012 | volume= | issue= | pages= | pmid=22628491 | doi=10.1378/chest.11-2739 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22628491 }} </ref> and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to [[pulmonary hypertension]]. | ||
==Subsegmental PEs== | |||
There is controversy over whether or not small subsegmental PEs need to be treated at all<ref name="pmid21949040">{{cite journal| author=Stein PD, Goodman LR, Hull RD, Dalen JE, Matta F| title=Diagnosis and management of isolated subsegmental pulmonary embolism: review and assessment of the options. | journal=Clin Appl Thromb Hemost | year= 2012 | volume= 18 | issue= 1 | pages= 20-6 | pmid=21949040 | doi=10.1177/1076029611422363 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21949040 }} </ref><ref>{{cite journal |author=Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F |title=Diagnosis and management of subsegmental pulmonary embolism |journal=J Thromb Haemost |volume=4 |issue=4 |pages=724-31 |year=2006 |pmid=16634736}}</ref> and some evidence exists that patients with subsegmental PEs may do well without treatment.<ref name="pmid16738276">{{cite journal |author=Perrier A, Bounameaux H |title=Accuracy or outcome in suspected pulmonary embolism |journal=N Engl J Med |volume=354 |issue=22 |pages=2383-5 |year=2006 |pmid=16738276|url=http://content.nejm.org/cgi/content/full/354/22/2383}}</ref><ref name="pmid16738268">{{cite journal |author=Stein P, Fowler S, Goodman L, Gottschalk A, Hales C, Hull R, Leeper K, Popovich J, Quinn D, Sos T, Sostman H, Tapson V, Wakefield T, Weg J, Woodard P |title=Multidetector computed tomography for acute pulmonary embolism |journal=N Engl J Med |volume=354 |issue=22 |pages=2317-27 |year=2006 |pmid=16738268}}</ref> | |||
===Predicting complications=== | |||
The PESI and Geneva prediction rules can estimate mortality and so may guide selection of patients who can be considered for outpatient therapy.<ref name="pmid17625081">{{cite journal |author=Jiménez D, Yusen RD, Otero R, ''et al'' |title=Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy |journal=Chest |volume=132 |issue=1 |pages=24-30 |year=2007 |pmid=17625081 |doi=10.1378/chest.06-2921}}</ref> | The PESI and Geneva prediction rules can estimate mortality and so may guide selection of patients who can be considered for outpatient therapy.<ref name="pmid17625081">{{cite journal |author=Jiménez D, Yusen RD, Otero R, ''et al'' |title=Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy |journal=Chest |volume=132 |issue=1 |pages=24-30 |year=2007 |pmid=17625081 |doi=10.1378/chest.06-2921}}</ref> | ||
Complications are more likely if [[heart rate]] is 100 bpm or more and if the [[D-dimer]] concentration > 3,000 microg/ml or more.<ref name="pmid19806253">{{cite journal| author=Agterof MJ, van Bladel ER, Schutgens RE, Snijder RJ, Tromp EA, Prins MH et al.| title=Risk stratification of patients with pulmonary embolism based on pulse rate and D-dimer concentration. | journal=Thromb Haemost | year= 2009 | volume= 102 | issue= 4 | pages= 683-7 | pmid=19806253 | |||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=19806253 | doi=10.1160/TH09-04-0229 }} </ref> | |||
===Evaluation for underlying causes for recurrence=== | ===Evaluation for underlying causes for recurrence=== |
Revision as of 10:57, 8 March 2024
Pulmonary embolism (PE) is form of embolism and thromboembolism in which a blockage of the pulmonary artery (or one of its branches), usually when a deep vein thrombosis (DVT; a blood clot from a vein), becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.[1] This process is termed thromboembolism.
Pathophysiology
The development of thrombosis is classically due to a group of causes named Virchow's triad (alterations in blood flow, factors in the vessel wall and factors affecting the properties of the blood). Often, more than one risk factor is present.
- Alterations in blood flow: immobilization (after surgery, injury or long-distance air travel), pregnancy (also procoagulant), obesity (also procoagulant)
- Factors in the vessel wall: of limited direct relevance in VTE
- Factors affecting the properties of the blood (procoagulant state):
- Estrogen-containing hormonal contraception
- Genetic thrombophilia (factor V Leiden, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and plasminogen/fibrinolysis disorders). The role of prothrombin mutation G20210A, is unclear.[2]
- Acquired thrombophilia (malignancy, antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria)
Diagnosis
The diagnosis of PE is based primarily on validated clinical criteria combined with selective testing because the typical clinical presentation (shortness of breath, chest pain) cannot be definitively differentiated from other causes of chest pain and shortness of breath.[3] Patients can present with atypical syndromes such as unexplained exacerbations of chronic obstructive pulmonary disease.[4]
Regarding chest pain, the pain may be pleuritic.[5][6][7] However, the reliability of assessing pleuritic may be low[8] and a meta-analysis concludes that assessing pleuritic pain is not helpful.[9]
D-dimer may be under-used in patients at low risk of pulmonary embolism.[10] Introduction of computed tomographic pulmonary angiography may have led to overdiagnosis of pulmonary embolism].[11]
Probability scoring
Various clinical prediction rules exist to help diagnose PE, such as the Wells score and the Geneva rule. More importantly, the use of any rule may exclude PE when combined with a normal d-dimer[12] and use of any rule might be associated with reduction in recurrent thromboembolism.[13]
Wells score
- History of the Wells score
The most commonly used method to predict clinical probability, the Wells score, is a clinical prediction rule, whose use is complicated by multiple versions being available. In 1995, Wells et al initially developed a prediction rule (based on a literature search) to predict the likelihood of PE, based on clinical criteria.[14] The prediction rule was revised in 1998[15] This prediction rule was further revised when simplified during a validation by Wells et al in 2000.[16] In the 2000 publication, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule.[16] In 2001, Wells published results using the more conservative cutoff of 2 to create three categories.[17] An additional version, the "modified extended version", using the more recent cutoff of 2 but including findings from Wells's initial studies[14][15] were proposed.[18] Most recently, studies (including one by Wells[19]) reverted to Wells's earlier use of a cutoff of ≤ 4 points[16] to create only two categories.[20][19]
- Wells score
The Wells score:[21]
- clinically suspected DVT - 3.0 points
- alternative diagnosis is less likely than PE - 3.0 points
- tachycardia (>100 bpm) - 1.5 points
- immobilization/surgery for 3 days ore more in previous four weeks - 1.5 points
- history of DVT or PE - 1.5 points
- hemoptysis - 1.0 points
- malignancy (treatment for within 6 months, palliative) - 1.0 points
- Interpretation of the Wells score
Traditional interpretation[16][17][22]
- Score >6.0 - High (probability 59% based on pooled data[23])
- Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data[23])
- Score <2.0 - Low (probability 4% to 15% based on pooled data[23])
Alternate interpretation[24][16][20][19]
- Score > 4 - PE likely. Consider diagnostic imaging.
- Score 4 or less - PE unlikely. Consider D-dimer to rule out PE.
Geneva score
The Geneva score also has several versions including the original version with 7 items that include blood gas and chest radiograph[25] the 'revised' version with 8 items using only signs and symptoms:[26]
Factor | Points |
---|---|
Risk factor | |
Age > 65 | 1 |
Previous PE or DVT | 3 |
Surgery under general anesthesia or lower-limb fracture within 1 month | 2 |
Malignancy (either active or considered cured within 1 year | 2 |
Symptoms | |
Unilateral lower-limb pain | 3 |
Hemoptysis | 2 |
Clinical signs | |
Heart rate 75-94 | 3 |
Heart rate > 94 | 5 |
Pain on lower-limb palpation and unilateral edema | 4 |
Points | Clinical probability | Prevalence of PE |
---|---|---|
0 -3 | Low | 8% |
4 - 10 | Intermediate | 29% |
> 10 | High | 74% |
More recently, a "Simplified revised version" assigns only one point to each sign and symptom. The simplified version, which gives one point to each of the following:[27]
- age over 65
- history of deep venous thrombosis or pulmonary embolism
- surgery under general anesthesia or lower-limb fracture within 1 month
- active malignancy
- unilateral lower-limb pain
- hemoptysis
- heart rate between 75 and 94 (give additional point if > 95)
- pain on lower-limb palpation and unilateral edema
In this version, a patient with a score of 2 or less is unlikely to have a pulmonary embolism during the next three months.
PERC
The Pulmonary Embolism Rule-out Criteria (PERC) may identify patients who are at such low risk that d-dimer testing is not needed in low (<15% prevalence)[28][29], but not medium (>20% prevalence)[30], risk populations.
Blood tests
In low/moderate suspicion of PE, a normal D-dimer level (shown in a blood test) is enough to exclude the possibility of thrombotic PE.[31][32][33] Unfortunately, many or even most doctors do not explicitly calculate pretest probability when interpreting the results of the d-dimer.[34]
Immunologic tests for d-dimer are generally use immunoassays such as enzyme-linked immunosorbent assay or serologic tests such as agglutination tests. The immunoassays (more specifically, enzyme-linked immunosorbent assay) tend to be more sensitive.[31]
sensitivity | specificity | |
---|---|---|
Immunoassays | ||
Elisa such as VIDAS™ | 95%[31] 96%[32] |
44%[31] 39%[32] |
Agglutination tests | ||
Latex agglutination such as Tinaquant™ | 89%[31] 96%[32] |
45%[31] 43%[32] |
Whole blood hemagglutination test such as SimpliRED™ | 78%[31] 87%[32] |
74%[31] 66%[32] |
Most patients with a pulmonary embolism have an abnormal alveolar-arterial oxygen gradient.[35]
Imaging
Pulmonary angiography
The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography. Pulmonary angiography is used less often due to wider acceptance of CT scans, which are non-invasive.
CT pulmonary angiography
Computed tomography with radiocontrast, also known as computed tomographic pulmonary angiography (CTPA), is increasingly used as the mainstay in diagnosis.[36] Advantages are clinical equivalence, its non-invasive nature, its greater availability to patients, and the possibility of detecting alternative diagnoses[37] from the differential diagnosis when there is no pulmonary embolism. CTPA has progressed to be available with 64 slices, each 0.625 mm thick. These machines take 3-4 seconds to scan and may be gated to the heart beat.
- Role in diagnosis
Assessing the accuracy of CT pulmonary angiography is hindered by the rapid changes in the number of rows of detectors available in multidetector CT (MDCT) machines.[38] The PIOPED II study used a mixture of 4 slice and 16 slice scanners and reported a sensitivity of 83% and a specificity of 96%. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging results.[39]
Location of embolism | Number of patients with true positive CTA |
Total number of patients with this finding on CTA |
Total number of patients with embolism in this location |
Positive predictive value of CTA |
---|---|---|---|---|
Any | 150 | 175 | 183 | 86% |
Embolism in a main or lobar artery | 116 | 120 | Not reported | 97% |
Segmental vessel | 32 | 47 | Not reported | 68% |
Subsegmental branch | 2 | 8 | Not reported | 25% |
- Role in Prognosis
Two systematic reviews[40][41] and two more recent randomized controlled trials[42][19] have studied prognosis after a negative CTPA.
Both systematic reviews concluded that is appears safe to withhold anticoagulation after a negative CTPA.[40][41] However, there may be two limitations to these conclusions. First, only one study in the two reviews has a pretest probability over 40%. Thus, these conclusions may not generalize to patients who are high risk in the three level Wells score. Second, many of the patients in these studies had additional tests such as leg dopplers as part of their evaluation so the results may not address CTPA as an individual test.
A more recent randomized controlled trial used d-dimer along with a mixture of 16 to 64 row detectors and found that adding imaging of the legs was not needed.[42] Among the patients included in this protocol, the prevalence of pulmonary embolism was 20.6%. All patients had either a d-dimer test or a leg ultrasonogram to help exclude pulmonary embolism.
A second randomized controlled trial was published after the two systematic reviews. This trial included patients with either patients with a Wells score of 4.5 or greater or a positive D-dimer assay result. The prevalence of pulmonary embolism during the initial evaluation was 14%. The trial found that CTPA, especially when multidector scans are used, increase the number of emboli found as compared to Ventilation/perfusion scan.[19] The importance of the increased detection is uncertain, but may be partly overdiagnosis.[43]
Ventilation/perfusion scan
Ventilation/perfusion scan (or V/Q scan or lung scintigraphy), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in patients who have an allergy to iodinated contrast or in pregnancy due to lower radiation exposure than CT.
For patients with a normal chest x-ray, doing a V/Q scan rather than computed tomographic pulmonary angiography may reduce radiation exposure.[44]
Chest X-ray
Chest X-rays are often done on patients with shortness of breath to help rule-out other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE are rarely normal,[45] but usually lack signs that suggest the diagnosis of PE (e.g. Westermark sign, Hampton's hump).
Magnetic resonance imaging
Magnetic resonance imaging with gadolinium has lower sensitivity than other methods and images are not always technically adequate.[46]
Ultrasonography of the legs
Ultrasonography or Duplex Doppler ultrasonography of the legs may help by diagnosing deep vein thrombosis (DVT) of the legs that may have led to pulmonary embolism. The presence of DVT, as shown on ultrasonography of the legs usually warrants anticoagulation, because of the strong association between DVT and PE.
Examining the legs may be valid approach in pregnancy, in x-rays might cause birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism.
Electrocardiogram findings
An ECG may show signs of right heart strain or acute cor pulmonale in cases of large PEs - the classic signs are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III ("S1Q3T3").[47][48] This is occasionally (up to 20%) present, but may also occur in other acute lung conditions and has therefore limited diagnostic value; the most commonly seen sign in the ECG is sinus tachycardia.
Echocardiography findings
In massive and submassive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the heart is unable to match the pressure. Some studies (see below) suggest that this finding may be an indication for thrombolysis. Not every patient with a (suspected) pulmonary embolism requires an echocardiogram, but elevations in cardiac troponins or brain natriuretic peptide may indicate heart strain and warrant an echocardiogram.[49]
The specific appearance of the right ventricle on echocardiography is referred to as the McConnell sign. This is the finding of akinesia of the mid-free wall but normal motion of the apex. This phenomenon has a 77% sensitivity and a 94% specificity for the diagnosis of acute pulmonary embolism.[50]
Combining tests into algorithms
Recent recommendations for a diagnostic algorithm have been published by the PIOPED II investigators; however, these recommendations do not reflect research using 64 slice MDCT.[51][23] These investigators recommended:
- Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer, obtain MDCT and based treatment on results.
- Moderate clinical probability. If negative D-dimer, PE is excluded. However, the authors were not concerned that a negative MDCT with negative D-dimer in this setting has an 5% probability of being false. Presumably, the 5% error rate will fall as 64 slice MDCT is more commonly used. If positive D-dimer, obtain MDCT and based treatment on results.
- High clinical probability. Proceed to MDCT. If positive, treat, if negative, addition tests are needed to exclude PE.
Treatment
In most cases, anticoagulant therapy is the mainstay of treatment. Some patients at risk of bleeding and with low risk of recurrent embolism may have treatment safely withheld.[52] Acutely, supportive treatments, such as oxygen or analgesia, are often required. See respiratory emergencies and critical care.
Anticoagulation
In most cases, anticoagulant therapy is the mainstay of treatment. Heparin, low molecular weight heparins (such as enoxaparin and dalteparin), or fondaparinux is administered initially, while warfarin therapy is commenced (this may take several days, usually while the patient is in hospital). Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. low molecular weight heparin. In patients with an underlying malignancy, therapy with a course of low molecular weight heparin may be favored over warfarin based on the results of the CLOT trial.[53] Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known teratogenic effects of warfarin.
Sometimes, anticoagulation may be done as an outpatient.[54][55][56][57]
Duration of treatment
Regarding the duration of anticoagulation, see embolism and thrombosis: treatment.
Vena cava filter
If anticoagulant therapy is contraindicated and/or ineffective an inferior vena cava filter may be implanted[58]; however, the risk-benefit is uncertain.[59]
A superior vena cava filter can be used for upper extremity thrombosis; however, the median survival is approximately one month.[60][61] A retrievable filter has been used.[62]
Thrombolysis
Clinical practice guidelines address the management of severe forms of embolism and thrombosis which may require thrombolysis.[63] An algorithm from the guidelines is online at http://circ.ahajournals.org/content/123/16/1788/F2.large.jpg. Massive PE causing hemodynamic instability (marked decreased oxygen saturation, tachycardia and/or hypotension) is an indication for thrombolysis, the enzymatic destruction of the clot with medication.
For submassive PE, some advocate thrombolysis if right ventricular dysfunction can be demonstrated on echocardiography.[64] However, an uncontrolled study suggests that submassive saddle PEs may not require thrombolysis.[65]
Thrombolysis can be given for severe PEs when surgery is not immediately available or possible (e.g. periarrest or during cardiac arrest). The only trial that addressed this issue had 8 patients; the four receiving thrombolysis survived, while the four who received only heparin died.[66] The use of thrombolysis in moderate PEs is still debatable. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or stroke.[67]
Surgical management of PE
Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is uncommon and has largely been abandoned because of poor long-term outcomes. However, recently, it has gone through a resurgence with the revision of the surgical technique and is thought to benefit selected patients.[68]
Chronic pulmonary embolism leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy.
Prognosis
Mortality from untreated PE is said to be 26% based on the outcome in patients who received placebo treatment.[69] The rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs.
With treatment, emboli resolve.[70] About half of emboli cannot be imaged after 10 days and about 80% cannot be imaged after one month.[70]
Prognosis depends on the amount of lung that is affected (embolic burden)[71] and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to pulmonary hypertension.
Subsegmental PEs
There is controversy over whether or not small subsegmental PEs need to be treated at all[72][73] and some evidence exists that patients with subsegmental PEs may do well without treatment.[74][39]
Predicting complications
The PESI and Geneva prediction rules can estimate mortality and so may guide selection of patients who can be considered for outpatient therapy.[75]
Complications are more likely if heart rate is 100 bpm or more and if the D-dimer concentration > 3,000 microg/ml or more.[76]
Evaluation for underlying causes for recurrence
After a first PE, the search for secondary causes is usually brief. Only when a second PE occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. This will include testing ("thrombophilia screen") for Factor V Leiden mutation, antiphospholipid antibodies, protein C and S and antithrombin levels, and later prothrombin mutation, MTHFR mutation, Factor VIII concentration and rarer inherited coagulation abnormalities.
References
- ↑ Tapson VF (March 2008). "Acute pulmonary embolism". N. Engl. J. Med. 358 (10): 1037–52. DOI:10.1056/NEJMra072753. PMID 18322285. Research Blogging.
- ↑ Segal JB, Brotman DJ, Necochea AJ, et al. (June 2009). "Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review". JAMA 301 (23): 2472–85. DOI:10.1001/jama.2009.853. PMID 19531787. Research Blogging.
- ↑ Chunilal SD, Eikelboom JW, Attia J, et al (2003). "Does this patient have pulmonary embolism?". JAMA 290 (21): 2849–58. DOI:10.1001/jama.290.21.2849. PMID 14657070. Research Blogging.
- ↑ Tillie-Leblond I, Marquette CH, Perez T, et al (March 2006). "Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors". Ann. Intern. Med. 144 (6): 390–6. PMID 16549851. [e]
- ↑ Stein PD, Beemath A, Matta F, Weg JG, Yusen RD, Hales CA et al. (2007). "Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II.". Am J Med 120 (10): 871-9. DOI:10.1016/j.amjmed.2007.03.024. PMID 17904458. PMC PMC2071924. Research Blogging. (uncontrolled case series)
- ↑ Hull RD, Raskob GE, Carter CJ, Coates G, Gill GJ, Sackett DL et al. (1988). "Pulmonary embolism in outpatients with pleuritic chest pain.". Arch Intern Med 148 (4): 838-44. PMID 3355304. [e]
- ↑ Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson BT et al. (1991). "Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.". Chest 100 (3): 598-603. PMID 1909617. [e]
- ↑ Kline JA, Nelson RD, Jackson RE, Courtney DM (2002). "Criteria for the safe use of D-dimer testing in emergency department patients with suspected pulmonary embolism: a multicenter US study.". Ann Emerg Med 39 (2): 144-52. PMID 11823768. [e]
- ↑ West J, Goodacre S, Sampson F (2007). "The value of clinical features in the diagnosis of acute pulmonary embolism: systematic review and meta-analysis.". QJM 100 (12): 763-9. DOI:10.1093/qjmed/hcm113. PMID 18089542. Research Blogging.
- ↑ Venkatesh AK, Kline JA, Courtney DM, Camargo CA, Plewa MC, Nordenholz KE et al. (2012). "Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure: Quantifying the Opportunity for ImprovementEvaluation of Pulmonary Embolism in ER.". Arch Intern Med: 1-5. DOI:10.1001/archinternmed.2012.1804. PMID 22664742. Research Blogging.
- ↑ Wiener RS, Schwartz LM, Woloshin S (2011). "Time trends in pulmonary embolism in the United States: evidence of overdiagnosis.". Arch Intern Med 171 (9): 831-7. DOI:10.1001/archinternmed.2011.178. PMID 21555660. PMC PMC3140219. Research Blogging.
- ↑ Douma RA, Mos IC, Erkens PM, Nizet TA, Durian MF, Hovens MM et al. (2011). "Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study.". Ann Intern Med 154 (11): 709-18. DOI:10.1059/0003-4819-154-11-201106070-00002. PMID 21646554. Research Blogging.
- ↑ 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.
- ↑ 14.0 14.1 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. DOI:doi:10.1016/S0140-6736(95)92535-X. PMID 7752753. Research Blogging.
- ↑ 15.0 15.1 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.
- ↑ 16.0 16.1 16.2 16.3 16.4 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.
- ↑ 17.0 17.1 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.
- ↑ 19.0 19.1 19.2 19.3 19.4 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. Research Blogging.
- ↑ 20.0 20.1 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. Research Blogging.
- ↑ Neff MJ (2003). "ACEP releases clinical policy on evaluation and management of pulmonary embolism". American family physician 68 (4): 759-60. PMID 12952389. [e]
- ↑ Yap KS, Kalff V, Turlakow A, Kelly MJ (2007). "A prospective reassessment of the utility of the Wells score in identifying pulmonary embolism". Med. J. Aust. 187 (6): 333–6. PMID 17874979. [e]
- ↑ 23.0 23.1 23.2 23.3 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. Research Blogging.
- ↑ Geersing, G.-J.; P. M. G. Erkens, W. A. M. Lucassen, H. R. Buller, H. t. Cate, A. W. Hoes, K. G. M. Moons, M. H. Prins, R. Oudega, H. C. P. M. van Weert, H. E. J. H. Stoffers (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 on 2012-10-05. Research Blogging.
- ↑ Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A (January 2001). "Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score". Arch. Intern. Med. 161 (1): 92–7. PMID 11146703. [e]
- ↑ Le Gal G, Righini M, Roy PM, et al (February 2006). "Prediction of pulmonary embolism in the emergency department: the revised Geneva score". Ann. Intern. Med. 144 (3): 165–71. PMID 16461960. [e]
- ↑ Klok FA, Mos IC, Nijkeuter M, et al (October 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. Research Blogging.
- ↑ Kline JA, Courtney DM, Kabrhel C, Moore CL, Smithline HA, Plewa MC et al. (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. Research Blogging.
- ↑ 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.". Am J Emerg Med 26 (2): 181-5. DOI:10.1016/j.ajem.2007.04.026. PMID 18272098. Research Blogging.
- ↑ Hugli O, Righini M, Le Gal G, Roy PM, Sanchez O, Verschuren F et al. (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. Research Blogging.
- ↑ 31.0 31.1 31.2 31.3 31.4 31.5 31.6 31.7 31.8 Stein PD, Hull RD, Patel KC, et al (April 2004). "D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review". Ann. Intern. Med. 140 (8): 589–602. PMID 15096330. [e]
ACP Journal Club review Cite error: Invalid
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tag; name "pmid15096330" defined multiple times with different content - ↑ 32.0 32.1 32.2 32.3 32.4 32.5 32.6 32.7 Di Nisio M, Squizzato A, Rutjes AW, Büller HR, Zwinderman AH, Bossuyt PM (February 2007). "Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review". J. Thromb. Haemost. 5 (2): 296–304. DOI:10.1111/j.1538-7836.2006.02328.x. PMID 17155963. Research Blogging.
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tag; name "pmid17155963" defined multiple times with different content - ↑ Gupta RT, Kakarla RK, Kirshenbaum KJ, Tapson VF (August 2009). "D-dimers and efficacy of clinical risk estimation algorithms: sensitivity in evaluation of acute pulmonary embolism". AJR Am J Roentgenol 193 (2): 425–30. DOI:10.2214/AJR.08.2186. PMID 19620439. Research Blogging.
- ↑ Smith C, Mensah A, Mal S, Worster A (November 2008). "Is pretest probability assessment on emergency department patients with suspected venous thromboembolism documented before SimpliRED D-dimer testing?". CJEM 10 (6): 519–23. PMID 19000347. [e]
- ↑ McFarlane MJ, Imperiale TF (1994). "Use of the alveolar-arterial oxygen gradient in the diagnosis of pulmonary embolism". Am. J. Med. 96 (1): 57–62. PMID 8304364. [e]
- ↑ Stein PD, Kayali F, Olson RE (May 2004). "Trends in the use of diagnostic imaging in patients hospitalized with acute pulmonary embolism". The American journal of cardiology 93 (10): 1316–7. DOI:10.1016/j.amjcard.2004.02.022. PMID 15135716. Research Blogging.
- ↑ Kim KI, Müller NL, Mayo JR (March 1999). "Clinically suspected pulmonary embolism: utility of spiral CT". Radiology 210 (3): 693–7. PMID 10207469. [e]
- ↑ Schaefer-Prokop C, Prokop M (2005). "MDCT for the diagnosis of acute pulmonary embolism". European radiology 15 Suppl 4: D37-41. PMID 16479644. [e]
- ↑ 39.0 39.1 39.2 Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD et al. (2006). "Multidetector computed tomography for acute pulmonary embolism.". N Engl J Med 354 (22): 2317-27. DOI:10.1056/NEJMoa052367. PMID 16738268. Research Blogging.
Review in: ACP J Club. 2006 Nov-Dec;145(3):76 Cite error: Invalid
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tag; name "pmid16738268" defined multiple times with different content - ↑ 40.0 40.1 Quiroz R, Kucher N, Zou KH, et al (April 2005). "Clinical validity of a negative computed tomography scan in patients with suspected pulmonary embolism: a systematic review". JAMA : the journal of the American Medical Association 293 (16): 2012–7. DOI:10.1001/jama.293.16.2012. PMID 15855435. Research Blogging.
- ↑ 41.0 41.1 Moores LK, Jackson WL, Shorr AF, Jackson JL (December 2004). "Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography". Annals of internal medicine 141 (11): 866–74. PMID 15583229. [e]
- ↑ 42.0 42.1 Righini M, Le Gal G, Aujesky D, et al (April 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. Research Blogging.
- ↑ Ranji SR, Shojania KG, Trowbridge RL, Auerbach AD (2006). "Impact of reliance on CT pulmonary angiography on diagnosis of pulmonary embolism: a Bayesian analysis". J Hosp Med 1 (2): 81-7. DOI:10.1002/jhm.71. PMID 17219477. Research Blogging.
- ↑ Stein EG, Haramati LB, Chamarthy M, Sprayregen S, Davitt MM, Freeman LM (2010). "Success of a safe and simple algorithm to reduce use of CT pulmonary angiography in the emergency department.". AJR Am J Roentgenol 194 (2): 392-7. DOI:10.2214/AJR.09.2499. PMID 20093601. Research Blogging.
- ↑ Worsley D, Alavi A, Aronchick J, Chen J, Greenspan R, Ravin C (1993). "Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study.". Radiology 189 (1): 133-6. PMID 8372182.
- ↑ Stein PD, Chenevert TL, Fowler SE, Goodman LR, Gottschalk A, Hales CA et al. (2010). "Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III).". Ann Intern Med 152 (7): 434-43, W142-3. DOI:10.1059/0003-4819-152-7-201004060-00008. PMID 20368649. Research Blogging.
- ↑ Miniati M, Bottai M, Monti S, Salvadori M, Serasini L, Passera M (August 2008). "Simple and accurate prediction of the clinical probability of pulmonary embolism". Am. J. Respir. Crit. Care Med. 178 (3): 290–4. DOI:10.1164/rccm.200802-207OC. PMID 18436792. Research Blogging.
- ↑ McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism. J Am Med Assoc 1935;104:1473–1480.
- ↑ Kucher N, Goldhaber SZ (2003). "Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism". Circulation 108 (18): 2191-4. DOI:10.1161/01.CIR.0000100687.99687.CE. PMID 14597581. Research Blogging.
- ↑ McConnell MV, Solomon SD, Rayan ME, Come PC, Goldhaber SZ, Lee RT (1996). "Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism". Am. J. Cardiol. 78 (4): 469-73. PMID 8752195. [e]
- ↑ Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD et al. (2006). "Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators.". Am J Med 119 (12): 1048-55. DOI:10.1016/j.amjmed.2006.05.060. PMID 17145249. Research Blogging.
- ↑ Stein PD, Hull RD, Raskob GE (September 2000). "Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial noninvasive leg tests". Am. J. Med. 109 (4): 301–6. PMID 10996581. [e]
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- ↑ Kovacs MJ, Anderson D, Morrow B, Gray L, Touchie D, Wells PS (February 2000). "Outpatient treatment of pulmonary embolism with dalteparin". Thromb. Haemost. 83 (2): 209–11. PMID 10739374. [e]
- ↑ Jiminez D, Yusen RD. Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy. Curr Opin Pulm Med. 2008 Sep;14(5):414-21. PMID 18664971
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- ↑ Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al. (2011). "Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association.". Circulation. DOI:10.1161/CIR.0b013e318214914f. PMID 21422387. Research Blogging.
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- ↑ Vedovati MC, Becattini C, Agnelli G, Kamphuisen PW, Masotti L, Pruszczyk P et al. (2012). "MULTIDETECTOR COMPUTED TOMOGRAPHY FOR ACUTE PULMONARY EMBOLISM: EMBOLIC BURDEN AND CLINICAL OUTCOME.". Chest. DOI:10.1378/chest.11-2739. PMID 22628491. Research Blogging.
- ↑ Stein PD, Goodman LR, Hull RD, Dalen JE, Matta F (2012). "Diagnosis and management of isolated subsegmental pulmonary embolism: review and assessment of the options.". Clin Appl Thromb Hemost 18 (1): 20-6. DOI:10.1177/1076029611422363. PMID 21949040. Research Blogging.
- ↑ Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F (2006). "Diagnosis and management of subsegmental pulmonary embolism". J Thromb Haemost 4 (4): 724-31. PMID 16634736.
- ↑ Perrier A, Bounameaux H (2006). "Accuracy or outcome in suspected pulmonary embolism". N Engl J Med 354 (22): 2383-5. PMID 16738276.
- ↑ Jiménez D, Yusen RD, Otero R, et al (2007). "Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy". Chest 132 (1): 24-30. DOI:10.1378/chest.06-2921. PMID 17625081. Research Blogging.
- ↑ Agterof MJ, van Bladel ER, Schutgens RE, Snijder RJ, Tromp EA, Prins MH et al. (2009). "Risk stratification of patients with pulmonary embolism based on pulse rate and D-dimer concentration.". Thromb Haemost 102 (4): 683-7. DOI:10.1160/TH09-04-0229. PMID 19806253. Research Blogging.
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