View source for Pulmonary embolism

''See [[pulmonary embolism in pregnancy]] for pregnancy specific information.''<ref>D-Dimer Concentrations in Normal Pregnancy: New Diagnostic Thresholds Are Needed. Kline et all. Clinical Chemistry May 2005 vol. 51 no. 5 825-829 http://www.clinchem.org/content/51/5/825.long</ref>

==Background==
[[File:Computed tomograph of pulmonary vessels.jpg|thumb|Pulmonary emboli can be classified according to the level along the pulmonary arterial tree.]]
{{Venous thromboembolism types}}

{{PE types}}

=== Epidemiology ===
* The best estimates indicate that 350,000 to 600,000 Americans each year suffer from DVT and PE<ref>Mozaffarien D et al.  Heart disease and stroke statistics - 2015 report from the American Heart Association. Circulation. 2015;131:d29-e322</ref>
* Survival<ref>U. S. Department of Health and Human Services. www.ncbi.nlm.nih.gov/blooks/NBK44178. The surgeon general's call to prevent deep vein thrombosis and pulmonary embolism.  2008</ref>
**PE is the 3rd leading cause of cardiovascular morbidity and mortality
**At least 100,000 deaths per year may be directly or indirectly related to DVT and PE
**For almost one quarter of PE patients, the initial clinical presentation is sudden death
**PE is an independent predictor of reduced survival for ≤3 months
**One of the leading causes of out-of-hospital, non-trauma related sudden deaths <ref>Tintinalli, J. E. (2016). Venous Thromboembolism In J.E. Tintinali (8th Ed.), Tintinalli's Emergency Medicine: A Comprehensive Study Guide  (pp. 389-390). New York, New York: McGraw Hill Education</ref>

==Clinical Features==
[[File:Deep vein thrombosis of the right leg.jpg|thumbnail|DVT of right leg]]
{{PE clinical presentation}}

==Differential Diagnosis==
{{Chest Pain DDX}}
{{SOB DDX}}

==Workup==
[[File:Pulm embolism.jpg|thumb|[[ECG]] of a person with pulmonary embolism, showing sinus tachycardia of approximately 100 beats per minute, large S wave in Lead I, moderate Q wave in Lead III, inverted T wave in Lead III, and inverted T waves in leads V1 and V3.]]
===Assessing Pretest Probability===
*''Objective criteria (Geneva, Wells, etc.) is equal to gestalt in assessing pre-test probability<ref name="ACEP">ACEP Clinical Policy for Pulmonary Embolism [http://www.acep.org/Content.aspx?id=80787/ full text]</ref> (ACEP Level B)''
*Initial Wells study and prospective validation <ref> Wolf SJ, et al. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med. 2004 Nov;44(5):503-10</ref> used a three tier system (low 0-1, intermediate 2-6, high >6) to establish pretest probability with a small sample size
*The larger Christopher Study group used a larger sample size to derive the simplified dichotomized/two tier model below<ref>van Belle A et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172-179. doi:10.1001/jama.295.2.172</ref>

{{Wells Score}}

===Low-Probability Testing in the ED===
*''[[PERC Rule]] negative'', then no further workup<ref name="ACEP" /> (ACEP Level B)
**Avoid CT pulmonary angiography in low pretest probability patients that are either PERC rule negative or have a negative d-dimer ([[Choosing wisely ACEP|ACEP choosing wisely]])
**D-dimer NPV is 99.5%<ref>Wells PS, Anderson DR, Rodger M, et al. 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</ref>
*''[[PERC Rule]] positive'', then [[D-dimer]] (see Moderate-Probability Testing below)<ref name="ACEP" />  (ACEP Level B)
**Can also consider using Wells score as above to determine further testing

===Adjusted D-Dimer to Higher Threshold===
*For certain patients a higher d-dimer can be used<ref>Flex your D-dimer Taming of the SRU http://www.tamingthesru.com/blog/diagnostics/flex-your-d-dimer</ref>
*[https://wikem.org/wiki/Age_adjusted_D-dimer Age Adjusted D-Dimer]
*[https://www.mdcalc.com/years-algorithm-pulmonary-embolism-pe YEARS Algorithm]
*[https://www.nejm.org/doi/full/10.1056/NEJMoa1909159 PEGeD]

===Less common risk factors===
*HIV (protein wasting nephropathy)
*[[Nephrotic Syndrome]]
*[[SLE]] with anti-cardiolipin Ab
*Exogenous hormones (specifically estrogen)
*homozygous [[Factor V Leiden]]
*Antithrombin III deficiency
*Protein C deficiency
*Protein S deficiency
*Hyperhomocysteinemia

===Evaluate bleeding risk (HAS-BLED)===
*HAS-BLED score (developed to evaluate bleeding risk for anticoagulation in Afib) can also identify patients with acute VTE at high risk for bleeding complications within 6 months<ref>Kooiman J et al. The HAS-BLED score identifies patients with acute venous thromboembolism at high risk of major bleeding complications during the first six months of anticoagulant treatment. PLOS ONE. 2015 Apr 23;10(4):e0122520. doi: 10.1371/journal.pone.0122520. eCollection 2015.</ref>
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Risk Factor'''
| align="center" style="background:#f0f0f0;"|'''Point'''
|-
| Hypertension||1
|-
| Abnormal renal and/or hepatic function||1 point each
|-
| Stroke||1
|-
| Bleeding tendency/predisposition||1
|-
| Labile INR on warfarin||1
|-
| Elderly (age >65 years)||1
|-
| Drugs (aspirin or NSAIDs) and/or alcohol||1 point each
|-
|}
*When applied to VTE patients on vitamin K-antagonists, NOT DOACs (in first 6 months of treatment):
**Score 0-2 = 1.3% incidence of major bleeds
**Score 3+ = 9.6% incidence of major bleeds
*Other bleeding risk models include the RIETE score (validated in patients taking VKA or rivaroxaban) and VTE-BLEED score (validated in patients taking warfarin and edoxaban).

===Initial Management While Awaiting Workup<ref>ACCP 9th Edition of the Antithrombotic Therapy Guidelines: Kearon C et al. Antithrombotic therapy for VTE disease. Chest. 2012;141:e419s – e494s. doi: 10.1378/chest.11-2301.</ref>===
*based on ACCP 2016 Guidelines
{| class="wikitable"
!Clinical suspicion !! Management
|-
| Low || Do not treat with anticoagulation while awaiting diagnostic test results
|-
| Medium || Treat with parenteral anticoagulation if the results of diagnostic tests are expected to be delayed ≥ 4 hours
|-
| High || Treat with parenteral anticoagulation while awaiting diagnostic test results
|-
|}

==Diagnosis==
[[File:SaddlePE.png|thumb|A large pulmonary embolism at the bifurcation of the pulmonary artery (saddle embolism).]]
===Definitive Diagnostic Imaging===
*CTA Chest if GFR >60
*V/Q scan if GFR <60
**Will be nondiagnostic if patient has effusion, pneumonia, or other airspace disease
*If imaging negative, perform additional diagnostic testing (e.g. lower extremity Doppler US, V/Q scan, and/or traditional pulmonary angiogram) prior to exclusion of VTE<ref name="ACEP" /> (ACEP Level C)
**A negative d-dimer in combination with a negative CTA theoretically provides a post-test probability of VTE less than 1%

===Other Possible Diagnostic Findings===
[[File:dsign.gif|thumb|D Sign<ref>http://www.thepocusatlas.com/right-ventricle</ref>]]
[[File:Hamptons.jpg|thumb|Hampton's Hump.]]
*[[ECG]] (abnormal in 70% of PE <ref>Marchick, MR et al. 12-lead ECG findings of pulmonary hypertension occur more frequently in emergency department patients with pulmonary embolism than in patients without pulmonary embolism. Ann Emerg Med. 2010 Apr;55(4):331-5.</ref> and associated with an adverse prognosis<ref>Agarwal A et al. Acute management of pulmonary embolism. https://www.acc.org/latest-in-cardiology/articles/2017/10/23/12/12/acute-management-of-pulmonary-embolism. 2017</ref>)
**T-wave inversions (34%)<ref>Co I, Eilbert W, Chiganos T. New Electrocardiographic Changes in Patients Diagnosed with Pulmonary Embolism. J Emerg Med. 2017 Mar;52(3):280-285. doi: 10.1016/j.jemermed.2016.09.009. Epub 2016 Oct 11. PMID: 27742402.</ref>
***Anterior/septal leads (V1-V4) and inferior leads<ref>Kosuge M, Kimura K, Ishikawa T, et al. Electrocardiographic differentiation between acute pulmonary embolism and acute coronary syndromes on the basis of negative T waves. Am J Cardiol 2007; 99: 817–821</ref>
**T-wave flattening (30%)
**Sinus Tachycardia (27%)
**Right axis deviation (11%)
**ST-segment changes in V1-V4 (9%)
**S1Q3T3 RV strain pattern (4%)
**New-onset atrial arrhythmias (e.g. atrial fibrillation)
**New RBBB (complete or incomplete) <ref>Shopo, JD et al. Findings from 12-lead electrocardiography that predict circulatory shock in pulmonary embolism; a systematic review and meta-analysis. Acad Emerg Med. 2015 Oct;22(10):1127-37</ref>
**QR pattern in V1
*[[CXR]] (abnormal in 70%)
**Atelectasis is most common (esp >24 hrs after onset of symptoms)
**Pleural effusion
**Hampton's Hump 
**Westermark's sign<ref>Sreenivasan S, Bennett S, Parfitt VJ. Images in cardiovascular medicine. Westermark's and Palla's signs in acute pulmonary embolism. Circulation. 2007 Feb 27;115(8):e211. [http://circ.ahajournals.org/content/115/8/e211.long full text]</ref> 
*[[Formal echocardiography|Formal transthoracic echo]] or [[Cardiac ultrasound|bedside cardiac ultrasound]]
**Can help diagnosis in equivocal cases
**May see signs of right heart strain (bowing of septum into LV; Aka D Sign)
***Right ventricular strain is associated with statistically significant worse outcome<ref>Taylor, RA, et al. Point-of-care focused cardiac ultrasound for prediction of pulmonary embolism adverse outcomes. The Journal of Emergency Medicine. 2013; 45(3):392–399.</ref>
**McConnell's sign- Right ventricular free wall akinesis that spares the apex
**Lateral right ventricular wall diameter of <5mm is suggestive of acute pulmonary hypertension while >5mm is suggestive of chronic pulmonary hypertension<ref>Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010; 23(7):685-713.</ref>
*SPECT 
**Combination of non-contrast CT chest with V/Q scan
**Avoidance of contrast for patients with renal injury
**As sensitive as CTPA and more sensitive than planar V/Q scanning<ref> Lu Y, Lorenzoni A, Fox JJ, Rademaker J, Vander Els N, Grewal RK, Strauss HW, Schöder H. Noncontrast perfusion single-photon emission CT/CT scanning: a new test for the expedited, high-accuracy diagnosis of acute pulmonary embolism. Chest. 2014 May;145(5):1079-88</ref>

==Management==
===Supportive care===
*Oxygen therapy (maintain SpO2 ≥90% unless otherwise indicated)
*Hemodynamic support (e.g. IVF, pressors)
**Consider gentle fluid challenge of 500ml normal saline bolus to improve cardiac index in select patients<ref>Mercat A et al. Hemodynamic effects of fluid loading in acute massive pulmonary embolism. Crit Care Med. 1999 Mar;27(3):540-4</ref>
**Experimental studies suggest that aggressive volume expansion provides little benefit and may worsen RV function in those with acutely elevated RV afterload and acutely increased pulmonary HTN<ref>Konstantinides SV et al. ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033-69 doi: 10.1093/eurheartj/ehu283</ref>

===Anticoagulation===
*Always consider [[Pulmonary_embolism#Evaluate_bleeding_risk_.28HAS-BLED.29|bleeding risk]] when determining risks/benefits of initiating anticoagulation
*Treatment options include any of the following anticoagulations which are indicated for all patients with confirmed [[PE]] or high clinical suspicion (do not wait for imaging).

{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Name'''
| align="center" style="background:#f0f0f0;"|'''[[LMWH]] SC'''
| align="center" style="background:#f0f0f0;"|'''[[Unfractionated Heparin]]'''
| align="center" style="background:#f0f0f0;"|'''[[Dabigatran]]'''
| align="center" style="background:#f0f0f0;"|'''[[Rivaroxaban]]'''
| align="center" style="background:#f0f0f0;"|'''[[Apixaban]]'''
| align="center" style="background:#f0f0f0;"|'''[[Coumadin]]'''
|-
|'''Initial Dose'''
||
*[[Enoxaparin]] 1mg/kg SC q12h 
*[[Dalteparin]] 200 IU/kg SC q24h, max 18,000 IU
||
*80 units/kg bolus; then 18 units/kg/hr continuous infusion
||
*Parenteral anticoagulation for 5-10 days; then 150mg twice daily
||
*15mg twice daily for 3 weeks, then 20mg once daily
||
*10mg twice daily for 1 week, then 5mg twice daily
||
*Cannot be administered alone for acute PE. Usual starting dose 5mg PO
|-
| '''Benefits'''
||
*1st line for most hemodynamically stable patients
*Preferred in those with cancer, liver disease, coagulopathy, pregnancy
||
*Short half-life
*Preferred if rapid reversal is needed (e.g. considering thrombolytics or with bleeding risk/trauma)
*No need for renal dosing 
||
*Noninferior to warfarin in reducing [[DVT]] and PE <ref>Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361(24):2342-52. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014; 129(7):764-72.</ref>
||
*Preferred if parenteral therapy to be avoided
*Associated with less bleeding, particularly in elderly patients and those with moderate renal impairment compared to standard treatments <ref>Hughes S. Rivaroxaban Stands up to standard anticoagulation for VTE treatment. Medscape Medical News. December 13, 2012.Buller HR, on behalf of the EINSTEIN Investigators. Oral rivaroxaban for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN [[DVT]] and EINSTEIN [[PE]] studies [abstract 20]. Presented at: 54th Annual Meeting and Exposition of the American Society of Hematology; December 8, 2012; Atlanta, Ga.</ref>
||
*Preferred if parenteral therapy to be avoided or if history of GI bleeding
*Studies show 16% reduction in VTE related death compared to standard therapy <ref>Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013; 369(9):799-808.Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013; 368(8):699-708.</ref>
||
*Preferred in renal disease, history of poor compliance, or history of GI bleed
|-
| '''Contraindications'''
||
*Severe renal impairment (CrCl <30 mL/min)
*Patients with morbid obesity or anasarca may have poor absorption
||
*Use with caution in patients >60yo
*Previous history of HIT
||
*Avoid in CAD and in severe renal impairment
||
*Avoid in hepatic disease (Child-Pugh Class B/C)
||
*Avoid in severe hepatic disease and renal impairment
||
*Temporary hypercoagulable state for approx 5 days
|-
| '''Comments'''
||
*Dose adjustments may be necessary in obese patients
||
*Check PTT after 6hr; adjust infusion to maintain PTT at 1.5-2.5x control
||
||
*Consider interactions with CYP3A4 inhibitors (e.g. -azoles)
||
*Consider interactions with CYP3A4 inhibitors
||
*INR target 2.5 
*Consider many drug-drug interactions with CYP450 inhibitors or inducers
|}

*Duration 
**3-6 mo, if time limited risk factor (post-op, trauma, estrogen use) 
**6 mo to life, if idiopathic etiology or recurrent

===Subsegmental PE===
*Evaluate for proximal DVT in legs with ultrasound
**If low risk for recurrent VTE: Clinical surveillance recommended over anticoagulation ([[EBQ:Evidence_Levels|Level 2C]] evidence)<ref>Kearon, Clive, et al. "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report." Chest (2016).[[http://www.cercp.org/images/stories/recursos/articulos_docs_interes/guia_tto_antitrombotico_tv_2016.pdf fulltext]]</ref>
**If high risk for recurrent VTE: anticoagulation recommended over surveillance

===Catheter-directed Therapy for intermediate-risk (submassive) PE<ref>Kucher N et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/circulationha.113.005544. Epub 2013 Nov 13</ref>===
*Includes catheter-directed thrombolysis and mechanical thrombus removal without thrombolysis
*Still no large prospective cohort or randomized trial evaluating CDT, so limited evidence recommendations from ACCP 2016 are weak
**Primary outcome measure in study of 59 patients was improved RV function at 24 hours, but not mortality
*Given broad clinical spectrum of intermediate-risk PE, CDT can be considered in a subset of patients with following characteristics:
**Intermediate-risk PE with more severe degree of RV dysfunction and positive biomarkers
**Intermediate-risk PE with severe hypoxemia
**High-risk (massive) PE with contraindications to systemic thrombolysis
*Complications include major access site bleeding, significant arrhythmias, pulmonary artery dissection, tamponade, worsening hemodynamics

===Thrombolysis===
*See [[Thrombolysis for PE]]
===[[IVC Filter]]===
*Indications
**anticoagulation contraindicated in patient with PE
**failure to attain adequate anticoagulation during treatment

==Disposition==
*Patients with significant clot burden generally require admission for anticoagulation
*Consider discharge in low risk patients with peripheral PE <ref>Vinson DR, Zehtabchi S, Yealy DM. Can selected patients with newly diagnosed pulmonary embolism be safely treated without hospitalization? A systematic review. Ann Emerg Med. 2012; 60:651-662.</ref> 
*Risk stratify which patients can be discharged using HESTIA<ref>Zondag et al. Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism. European Respiratory Journal. 2013; 41:588-592.</ref>, sPESI, or PESI scores<ref>Maughan et al. Outpatient Treatment of Low‐risk Pulmonary Embolism in the Era of Direct Oral Anticoagulants: A Systematic Review Academic Emergency Medicine 2021; 28: 226– 239. https://doi.org/10.1111/acem.14108</ref>.

==Prognosis==
The Pulmonary Embolism Severity Index (PESI)<ref>Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:1041-1046.</ref>
*PE patients with PESI class I or II seem safe to manage as outpatients.
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Prognosis Variable'''
| align="center" style="background:#f0f0f0;"|'''Points Assigned'''
|-
| '''Demographics'''||
|-
| Age||+Age in years
|-
| Male||+10
|-
| '''Comorbid Conditions'''||
|-
| Cancer||+30
|-
| Heart Failure||+10
|-
| Chronic Lung Disease||+10
|-
| '''Clincal Findings'''||
|-
| Pulse >110 b/min||+20
|-
| sBP < 100||+30
|-
| RR > 30||+20
|-
| Temp <36 C||+20
|-
| AMS||+60
|-
| Art O2 Saturation <90%||+20
|-
|}

{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Risk Class'''
| align="center" style="background:#f0f0f0;"|'''30-Day Mortality'''
| align="center" style="background:#f0f0f0;"|'''Total Point Score'''
|-
| I||1.60%||<65
|-
| II||3.50%||66-85
|-
| III||7.10%||86-105
|-
| IV||11.40%||106-125
|-
| V||23.90%||>125
|-
|}

==See Also==
*[[Pulmonary Embolism in Pregnancy]]
*[[IVC Filter]]
*[[Cardiac ultrasound]]
{{Thrombolysis Submassive PE Trials}}

==External Links==
*[https://www.acep.org/patient-care/clinical-policies/acute-venous-thromboembolic-disease/ ACEP Clinical Policy: Acute Venous Thromboembolic Disease (Feb 2018)]
*[https://www.mdcalc.com/calc/1247/simplified-pesi-pulmonary-embolism-severity-index MDCalc Simplified PESI]
*[http://www.mdcalc.com/wells-criteria-for-pulmonary-embolism-pe/ MDCalc - Well's Criteria for Pulmonary Embolism]
*[http://www.mdcalc.com/perc-rule-for-pulmonary-embolism/ MDCalc - PERC Rule for Pulmonary Embolism]
*[http://www.mdcalc.com/geneva-score-revised-for-pulmonary-embolism/ MDCalc - Geneva Score for Pulmonary Embolism]
*[http://www.mdcalc.com/pulmonary-embolism-severity-index-pesi/  MDCalc - PESI - Pulmonary Embolism Severity Index]
*[https://www.mdcalc.com/hestia-criteria-outpatient-pulmonary-embolism-treatment#evidence/ MDCalc - Hestia Criteria for Pulmonary Embolism]
*[https://www.mdcalc.com/has-bled-score-major-bleeding-risk/ MDCalc - HAS-BLED Score for major bleeding risk]

==References==
{{Reflist|2}}

[[Category:Cardiology]]
[[Category:Pulmonary]]
[[Category:Vascular]]