Pulmonary embolism

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Pulmonary embolism
Classification & external resources

ICD-10	I26.0, I26.9
ICD-9	415.1
DiseasesDB	10956
MedlinePlus	000132
eMedicine	med/1958

Pulmonary embolism is blockage of the pulmonary artery (or one of its branches) by a blood clot, fat, air or clumped tumor cells. By far the most common form of pulmonary embolism is a thromboembolism, which occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.

Symptoms may include difficulty breathing, pain during breathing, and more rarely circulatory instability and death. Treatment, usually, is with anticoagulant medication, such as warfarin. Other rarer forms of pulmonary embolism occur when material other than a blood clot is responsible. Such materials can include fat or bone (usually in association with significant trauma), air (often when diving), and amniotic fluid (affecting mothers during childbirth).

Contents 1 Signs, symptoms and risk factors 1.1 Clinical presentation 1.2 Risk factors 2 Diagnosis 2.1 Clinical criteria 2.2 Blood work 2.3 Medical imaging 2.3.1 Imaging to evaluate for pulmonary embolism 2.3.2 Low probablitity diagnostic tests/non-diagnostic tests 2.4 Electrocardiogram findings 2.5 Echocardiography findings 3 Treatment 3.1 Medical management 3.2 Thrombolysis 3.3 Surgical management of PE 4 Prognosis 5 References

[edit] Signs, symptoms and risk factors

[edit] Clinical presentation

Signs of PE are sudden-onset dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain of "pleuritic" nature (worsened by breathing), cough, hemoptysis (coughing up blood), and in severe cases, cyanosis ("turning blue" due to lack of oxygen entering the bloodstream), tachycardia (rapid heart rate), hypotension, shock, loss of consciousness, and death. Although most cases have no clinical evidence of deep venous thrombosis (DVT) in the legs, findings that indicate DVT may aid in the diagnosis.

[edit] Risk factors

The most common sources of embolism are 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, 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, 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)

[edit] 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.

[edit] Clinical criteria

The decision to do medical imaging is usually based on clinical grounds, i.e. the medical history, symptoms and findings on physical examination.

In 2000, Wells et al.^[1] developed a frequently used scoring system to predict the likelihood of PE, based on clinical criteria.

The Wells score:^[2]

• 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

Interpretation:

Traditional interpretation

Score >6.0 - High

Score 2.0 to 6.0 - Moderate

Score <2.0 - Low

New proposed interpretation^[3]

Score > 4 - PE likely. Consider CT pulmonary angiography.

Score 4 or less - PE unlikely. Consider D-dimer testing by ELISA to rule out PE.

[edit] Blood work

In low/moderate suspicion of PE, a normal D-dimer level (shown in a blood test) is enough to exclude the possibility of PE.^[4]

When a PE is being suspected, a number of blood tests are done, in order to exclude important secondary causes of PE. This includes a full blood count, clotting status (PT, APTT, TT), and some screening tests (erythrocyte sedimentation rate, renal function, liver enzymes, electrolytes). If one of these is abnormal, further investigations might be warranted.

[edit] Medical imaging

The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography. Pulmonary angiography is used less often because of wider acceptance of CT scans, which are non-invasive.

[edit] Imaging to evaluate for pulmonary embolism

• Computed tomography with radiocontrast, effectively a pulmonary angiogram imaged by CT and known as CT pulmonary angiography (CTPA), is increasingly used as the mainstay in diagnosis.^[5] Advantages are clinical equivalence, its non-invasive nature, its greater availability to patients, and the possibility of picking up other lung disorders from the differential diagnosis in case there is no pulmonary embolism.
• Ventilation/perfusion scan (or V/Q scan), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). It is a type of scintigraphy. This study is used less often because 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.

[edit] Low probablitity diagnostic tests/non-diagnostic tests

Tests that are frequently done that are not sensitive for PE, but can be diagnostic.

• 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,^[6] but usually lack signs that suggest the diagnosis of PE (e.g. Westermark sign, Hampton's hump).
• Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT). The presence of 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.

[edit] Electrocardiogram findings

An electrocardiogram (ECG) is routinely done on patients with chest pain to quickly diagnose myocardial infarctions (heart attacks). 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").^[7] 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.

[edit] Echocardiography findings

In massive 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. In the United States, many physicians see this as an adequate indication for thrombolysis (see below).

[edit] Treatment

Acutely, supportive treatments, such as 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.^[8]

[edit] Medical management

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 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. 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.^[9] Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known teratogenic effects of warfarin. If anticoagulant therapy is contraindicated and/or ineffective an inferior vena cava filter may be implanted.

[edit] 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.^[10] 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.^[11]

[edit] 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.^[12]

Chronic pulmonary embolism leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy.

[edit] Prognosis

Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan^[13] 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 the fact that with the technology of the day, only severe PEs were detected.

Prognosis depends on the amount of lung that is affected and on the co-existence of other debilitating 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^[14] and there exists some current medical evidence that patients with subsegmental PEs may in fact do quite well without treatment.^[15][16]

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.

[edit] References

1. ^ 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. 
2. ^ Neff MJ. ACEP releases clinical policy on evaluation and management of pulmonary embolism. American Family Physician. 2003; 68(4):759-?. Available at: http://www.aafp.org/afp/20030815/practice.html. Accessed on: December 8, 2006.
3. ^ 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. 
4. ^ Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 1994;71:1-6. PMID 8165626.
5. ^ PIOPED II investigators. Multidetector computed tomography for Acute Pulmonary Embolism. N Engl J Med 2006,354;22:2317-2327
6. ^ 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. 
7. ^ McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism. J Am Med Assoc 1935;104:1473–1480.
8. ^ Goldhaber SZ. Pulmonary embolism. Lancet 2004;363:1295-305. PMID 15094276.
9. ^ Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M (2003). "Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.". N Engl J Med 349 (2): 146-53. PMID 12853587. 
10. ^ 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.
11. ^ Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev 2006;(2):CD004437. PMID 16625603.
12. ^ Augustinos P, Ouriel K (2004). "Invasive approaches to treatment of venous thromboembolism". Circulation 110 (9 Suppl 1): I27-34. PMID 15339878. 
13. ^ (1960) "Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.". Lancet 1: 1309–1312. PMID 13797091. 
14. ^ 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. 
15. ^ Perrier A, Bounameaux H (2006). "Accuracy or outcome in suspected pulmonary embolism". N Engl J Med 354 (22): 2383-5. PMID 16738276.  Full Text.
16. ^ 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 (2006). "Multidetector computed tomography for acute pulmonary embolism". N Engl J Med 354 (22): 2317-27. PMID 16738268.