Pulmonary embolism 207165 224626073 2008-07-09T18:38:59Z 68.236.177.118 /* Echocardiography findings */ {{Infobox_Disease | Name = Pulmonary embolism | Image = | Caption = | DiseasesDB = 10956 | ICD10 = {{ICD10|I|26||i|26}} | ICD9 = {{ICD9|415.1}} | ICDO = | OMIM = | MedlinePlus = 000132 | eMedicineSubj = med | eMedicineTopic = 1958 | eMedicine_mult = {{eMedicine2|emerg|490}} {{eMedicine2|radio|582}} | MeshID = D011655 | }} '''Pulmonary embolism''' (PE) is a blockage of the [[pulmonary artery]] or one of its branches, usually occuring when a [[vein|venous]] [[thrombus]] (blood clot from a vein) becomes dislodged from its site of formation and [[embolism|embolizes]] to the [[pulmonary artery|arterial]] blood supply of one of the lungs. This process is termed ''thromboembolism''. Symptoms may include [[dyspnea|difficulty breathing]], [[pain]] [[chest pain|in the chest]] during breathing, and in more severe cases [[Collapse (medical)|collapse]], [[Shock (medical)|circulatory instability]] and [[cardiac arrest|sudden death]]. Treatment, usually, is with [[anticoagulant]] medication, such as [[heparin]] and [[warfarin]], and rarely (in severe cases) with [[thrombolysis]] or surgery. In other, rarer forms of pulmonary embolism, material other than a blood clot is responsible; this may include [[Lipid|fat]] or [[bone]] (usually in association with significant trauma), [[air]] (often when [[Underwater diving|diving]]), clumped [[tumor cell]]s, and [[amniotic fluid]] (affecting [[mother]]s during [[childbirth]]). ==Signs and symptoms== Symptoms of PE are sudden-onset [[dyspnea]] (shortness of breath), [[tachypnea]] (rapid breathing), [[chest pain]] of a "pleuritic" nature (worsened by breathing), [[cough]], [[hemoptysis]] (coughing up blood), and may aid in the diagnosis. More severe cases can include signs such as pleural rub, [[cyanosis]] (blue discoloration, usually of the lips and fingers), [[Collapse (medical)|collapse]], and [[Shock (medical)|circulatory instability]]. About 15% of all cases of [[Sudden cardiac death|sudden death]] are attributable to PE. ==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. The decision to do medical imaging is usually based on clinical grounds, i.e. the [[medical history]], symptoms and findings on [[physical examination]]. The most commonly used method to predict clinical probability, the [[Wells score]], is [[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=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 | 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, a further study 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> There are additional prediction rules for PE, such as the [[Geneva rule]]. More importantly, the use of ''any'' rule is associated with reduction in recurrent thromboembolism.<ref name="pmid16461959">{{cite journal |author=Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A |title=Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism |journal=Ann. Intern. Med. |volume=144 |issue=3 |pages=157–64 |year=2006 |pmid=16461959}}</ref> ''The 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 [[DVT]] - 3.0 points *alternative diagnosis is less likely than PE - 3.0 points *tachycardia - 1.5 points *immobilization/surgery 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 Traditional interpretation<ref name="pmid10744147"/><ref name="pmid11453709"/><ref name="pmid17874979">{{cite journal |author=Yap KS, Kalff V, Turlakow A, Kelly MJ |title=A prospective reassessment of the utility of the Wells score in identifying pulmonary embolism |journal=Med. J. Aust. |volume=187 |issue=6 |pages=333–6 |year=2007 |pmid=17874979 |doi=}}</ref> * Score >6.0 - High (probability 59% based on pooled data<ref name="pmid17185658">{{cite journal |author=Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD |title=Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators |journal=Radiology |volume=242 |issue=1 |pages=15–21 |year=2007 |doi=10.1148/radiol.2421060971 | pmid=17185658}}</ref>) * Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data<ref name="pmid17185658"/>) * Score <2.0 - Low (probability 15% based on pooled data<ref name="pmid17185658"/>) Alternate interpretation<ref name="pmid10744147"/><ref name="pmid16403929"/> * Score > 4 - PE likely. Consider diagnostic imaging. * Score 4 or less - PE unlikely. Consider [[D-dimer]] to rule out PE. ===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="pmid8165626">{{cite journal |author=Bounameaux H, de Moerloose P, Perrier A, Reber G |title=Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview |journal=Thromb. Haemost. |volume=71 |issue=1 |pages=1–6 |year=1994 |pmid=8165626 |doi=}}</ref> When a PE is being suspected, a number of [[blood test]]s are done, in order to exclude important secondary causes of PE. This includes a [[full blood count]], [[coagulation|clotting status]] ([[prothrombin time|PT]], [[APTT]], [[thrombin time|TT]]), and some screening tests ([[erythrocyte sedimentation rate]], [[renal function]], [[liver enzyme]]s, [[electrolyte]]s). If one of these is abnormal, further investigations might be warranted. ===Medical imaging=== The [[gold standard (test)|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. ;Non-invasive imaging [[CT pulmonary angiogram|CT pulmonary angiography]] (CTPA) is a [[pulmonary angiogram]] obtained using [[computed tomography]] (CT) with [[radiocontrast]] rather than right heart catheterization. Its advantages are clinical equivalence, its non-invasive nature, its greater availability to patients, and the possibility of identifying other lung disorders from the [[differential diagnosis]] in case there is no pulmonary embolism. 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> A study with a mixture of 4 slice and 16 slice scanners 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, ''et al'' |title=Multidetector computed tomography for acute pulmonary embolism |journal=N. Engl. J. Med. |volume=354 |issue=22 |pages=2317–27 |year=2006 |pmid=16738268 |doi=10.1056/NEJMoa052367}}</ref> CTPA is non-inferior to VQ scanning, and identifies more emboli (without necessarily improving the outcome) compared to VQ scanning.<ref name=Anderson2007>{{cite journal|author=Anderson DR, Kahn SR, Rodger MA ''et al''|year=2007|title=Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism|journal=JAMA|volume=298|issue=23|pages=2743–53|doi= 10.1001/jama.298.23.2743|pmid=18165667}}</ref> ''[[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.<ref>{{cite journal |author=Scarsbrook AF, Gleeson FV |title=Investigating suspected pulmonary embolism in pregnancy |journal=BMJ |volume=334 |issue=7590 |pages=418–9 |year=2007 |pmid=17322258 |doi=10.1136/bmj.39071.617257.80|url=http://www.bmj.com/cgi/content/full/334/7590/418}}</ref> ;Low probability diagnostic tests/non-diagnostic tests Tests that are frequently done that are not [[sensitivity (tests)|sensitive]] for PE, but can be diagnostic. *''[[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 | pmid = 8372182}}</ref> but usually lack [[radiologic sign|sign]]s that suggest the diagnosis of PE (e.g. [[Westermark sign]], [[Hampton's hump]]). *''[[medical ultrasound|Ultrasonography]] of the legs'', also known as ''leg doppler'', in search of [[deep venous thrombosis]] (DVT). The presence of [[deep venous thrombosis|DVT]], as shown on [[ultrasonography]] of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be valid approach in [[pregnancy]], in which the other modalities would increase the risk of 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 [[electrocardiogram]] (ECG) is routinely done on patients with chest pain to quickly diagnose [[myocardial infarction]]s (heart attacks). 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>{{cite journal | author=McGinn S, [[Paul Dudley White|White PD]] | title=Acute cor pulmonale resulting from pulmonary embolism | journal=J Am Med Assoc | year= 1935 | volume=104 | pages=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 signs in the ECG is sinus tachycardia, right axis deviation and right bundle branch block.<ref>{{cite journal |author=Rodger M, Makropoulos D, Turek M, ''et al'' |title=Diagnostic value of the electrocardiogram in suspected pulmonary embolism |journal=Am. J. Cardiol. |volume=86 |issue=7 |pages=807–9, A10 |year=2000 |month=October |pmid=11018210 |doi=10.1016/S0002-9149(00)01090-0}}</ref> ===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 [[troponin|cardiac troponins]] or [[brain natriuretic peptide]] may indicate heart strain and warrant an echocardiogram.<ref>{{cite journal |author=Kucher N, Goldhaber SZ |title=Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism |journal=Circulation |volume=108 |issue=18 |pages=2191–4 |year=2003 |pmid=14597581 |doi=10.1161/01.CIR.0000100687.99687.CE}}</ref> 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.<ref>{{cite journal |author=McConnell MV, Solomon SD, Rayan ME, Come PC, Goldhaber SZ, Lee RT |title=Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism |journal=Am. J. Cardiol. |volume=78 |issue=4 |pages=469–73 |year=1996 |pmid=8752195|doi=10.1016/S0002-9149(96)00339-6}}</ref> ===Combining tests into algorithms=== Recent recommendations for a diagnostic algorithm have been published by the PIOPED investigators; however, these recommendations do not reflect research using 64 slice MDCT.<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. * 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. Acutely, supportive treatments, such as [[oxygen therapy|oxygen]] or [[analgesia]], are often required. 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. Some advocate its use also if right ventricular dysfunction can be demonstrated on [[echocardiography]].<ref>{{cite journal | author=Goldhaber SZ | title=Pulmonary embolism | journal=Lancet | year=2004 | volume=363 | pages=1295–305 | pmid=15094276 | doi=10.1016/S0140-6736(04)16004-2}}</ref> ===Anticoagulation=== {{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 | pmid=12853587 | doi=10.1056/NEJMoa025313}}</ref> Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known [[teratogenic]] effects of warfarin, especially in the early stages of pregnancy. People are usually admitted to hospital in the early stages of treatment, and tend to remain under inpatient care until INR has reached therapeutic levels. Increasingly, low-risk cases are managed on an outpatient basis in a fashion already common in the treatment of DVT.<ref>{{cite journal |author=Davies CW, Wimperis J, Green ES, ''et al'' |title=Early discharge of patients with pulmonary embolism: a two-phase observational study |journal=Eur. Respir. J. |volume=30 |issue=4 |pages=708–14 |year=2007 |month=October |pmid=17567672 |doi=10.1183/09031936.00140506}}</ref> Warfarin therapy is usually continued for 3-6 months, or "lifelong" if there have been previous DVTs or PEs, or none of the usual risk factors is present. An abnormal [[D-dimer]] level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked pulmonary embolus.<ref name="pmid17065639">{{cite journal |author=Palareti G, Cosmi B, Legnani C, ''et al'' |title=D-dimer testing to determine the duration of anticoagulation therapy |journal=N. Engl. J. Med. |volume=355 |issue=17 |pages=1780–9 |year=2006 |pmid=17065639 |doi=10.1056/NEJMoa054444}}</ref> [[Image:Mar07 090.jpg|thumb|left|300px|Used inferior vena cava filter, presented with a [[British twenty pence coin]] for scale.]] ===Inferior vena cava filter=== {{main|inferior vena cava filter}} If anticoagulant therapy is [[contraindication|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 |pmid=9459643 |doi=10.1056/NEJM199802123380701}}</ref> ===Thrombolysis=== {{main|Thrombolysis}} [[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> ===Surgical management=== 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.<ref>{{cite journal | author=Augustinos P, Ouriel K | title=Invasive approaches to treatment of venous thromboembolism | journal=Circulation | year=2004 | volume=110 | issue=9 Suppl 1 | pages=I27–34 | pmid=15339878 | doi=10.1161/01.CIR.0000140900.64198.f4}}</ref> 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%. This figure comes from a trial published in [[1960]] by Barrit and Jordan,<ref name="Barritt">{{cite journal|author=Barritt DW, Jordan SC | title=Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. | journal=[[The Lancet|Lancet]] | year=1960 | volume=1 | pages=1309&ndash;1312 | pmid=13797091 | doi=10.1016/S0140-6736(60)92299-6 }}</ref> which compared anticoagulation against placebo for the management of PE. Barritt and Jordan performed their study in the [[Bristol Royal Infirmary]] in 1957. This study is the only placebo controlled trial ever to examine the place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs. Prognosis depends on the amount of lung that is affected and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to [[pulmonary hypertension]]. There is controversy over whether or not small subsegmental PEs need to be treated at all<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 |doi=10.1111/j.1538-7836.2006.01819.x}}</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 |doi=10.1056/NEJMe068076}}</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 |doi=10.1056/NEJMoa052367}}</ref> ===Predicting mortality=== 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> ===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. ==Epidemiology== ===Risk factors=== The most common sources of embolism are [[Anatomical terms of location#Proximal and distal|proximal]] leg [[deep venous thrombosis]] (DVTs) or pelvic vein thromboses. Any risk factor for DVT also increases the risk that the venous clot will dislodge and migrate to the lung circulation, which happens in up to 15% of all DVTs. The conditions are generally regarded as a continuum termed [[venous thromboembolism]] (VTE). 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, [[Physical trauma|injury]] or [[Economy class syndrome|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]], [[prothrombin]] mutation G20210A, [[protein C deficiency]], [[protein S deficiency]], [[antithrombin]] deficiency, [[hyperhomocysteinemia]] and [[plasminogen]]/[[fibrinolysis]] disorders). ** Acquired thrombophilia ([[antiphospholipid syndrome]], [[nephrotic syndrome]], [[paroxysmal nocturnal hemoglobinuria]]) ==References== {{Reflist|2}} ==External links== * [http://rad.usuhs.edu/medpix/medpix.html?mode=image_finder&action=search&srchstr=pulmonary%20embolism&srch_type=all#top Images of Pulmonary Embolism] * [http://www.natfonline.org/ North American Thrombosis Forum] - NATF is a nonprofit organization that aims to promote public education, policy and advocacy for clotting diseases of the cardiovascular system. {{Vascular diseases}} [[Category:Hematology]] [[Category:Pulmonology]] [[bn:ফুসফুসীয় ধমনীরোধ]] [[cs:Plicní embolie]] [[da:Lungeemboli]] [[de:Lungenembolie]] [[es:Tromboembolismo pulmonar]] [[eo:Pulma embolio]] [[eu:BTE]] [[fr:Embolie pulmonaire]] [[ko:폐색전증]] [[it:Embolia polmonare]] [[nl:Longembolie]] [[no:Lungeemboli]] [[pl:Zatorowość płucna]] [[pt:Embolia pulmonar]] [[simple:Pulmonary embolism]] [[sr:Плућна емболија]]