Pulmonary embolism: Difference between revisions

(Text replacement - "1 mg" to "1mg")
 
(140 intermediate revisions by 25 users not shown)
Line 1: Line 1:
''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>
''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==
==Background==
{{Venous thromboembolism types}}
Pulmonary embolism is an obstruction of one of the branches of the pulmonary arteries by material; typically a thrombus
*[[Fat_embolism_syndrome|Fat]], [[Arterial_gas_embolism|Air]], and tumor embolisms can similarly and obstruct a branch of the pulmonary artery, but are not covered in this section
*A pulmonary embolism is on the spectrum of [[Venous_thromboembolism|Venous thromboembolism (VTE)]]
*Most emboli are thought to arise from lower extremity proximal veins (iliac, femoral, and popliteal), whereas a thrombus of the distal veins (calf) resolves spontaneously ⅔ of the time <ref> Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I22-I30. doi:10.1161/01.CIR.0000078464.82671.78 </ref> <ref> Lautz TB, Abbas F, Walsh SJ, et al. Isolated gastrocnemius and soleal vein thrombosis: should these patients receive therapeutic anticoagulation?. Ann Surg. 2010;251(4):735-742. doi:10.1097/SLA.0b013e3181c1ae95 </ref> <ref> Macdonald PS, Kahn SR, Miller N, Obrand D. Short-term natural history of isolated gastrocnemius and soleal vein thrombosis. J Vasc Surg. 2003;37(3):523-527. doi:10.1067/mva.2003.149 </ref>


{{PE types}}
[[File:Computed tomograph of pulmonary vessels.jpg|thumb|Pulmonary emboli can be classified according to the level along the pulmonary arterial tree.]]
 
=== Epidemiology ===
*In the US, approximately 370,000-390,000 PE’s are diagnosed annually <ref> Freund Y, Cohen-Aubart F, Bloom B. Acute Pulmonary Embolism: A Review. JAMA. 2022;328(13):1336-1345. doi:10.1001/jama.2022.16815 </ref> <ref> Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023;147(8):e93-e621. doi:10.1161/CIR.0000000000001123 </ref>
*Mortality
**Hemodynamically stable (AHA/ACC Class A & B or ESC Low Risk) patients with a PE have a direct mortality of about 1%, however hemodynamically unstable patients mortality ranges from 25-50% <ref> Schultz J, Giordano N, Zheng H, et al. EXPRESS: A Multidisciplinary Pulmonary Embolism Response Team (PERT) - Experience from a national multicenter consortium. Pulm Circ. Published online January 11, 2019. doi:10.1177/2045894018824563 </ref>
**For almost one quarter of PE patients, the initial clinical presentation is sudden death <ref> Walls R, Hockberger R, Gausche-Hill M, Erickson TB, & Wilcox SR. (2022). Rosen's Emergency Medicine - Concepts and Clinical Practice E-Book (10th ed.). Elsevier - OHCE. </ref>


==Clinical Features==
==Clinical Features==
[[File:Deep vein thrombosis of the right leg.jpg|thumbnail|DVT of right leg]]
* Diagnosis of PE is challenging, with less than 10% of patients evaluated for a PE ultimately diagnosed with a PE <ref>  Creager MA, Barnes GD, et al. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. Published online February 19, 2026. doi:10.1161/CIR.0000000000001415 </ref>
{{PE clinical presentation}}
{{PE clinical presentation}}


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


==Diagnostic Evaluation==
==Workup==
===Wells Criteria===
[[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.]]
{{Wells Criteria}}
===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'''
{{Wells Score}}
{{Wells Score}}


===Less common risks===
===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)
*HIV (protein wasting nephropathy)
*[[Nephrotic Syndrome]]
*[[Nephrotic Syndrome]]
*[[SLE]] with anti-cardiolipan Ab
*[[SLE]] with anti-cardiolipin Ab
*Exogenous hormones
*Exogenous hormones (specifically estrogen)
*homozygous [[Factor V Leiden]]
*Antithrombin III deficiency
*Protein C deficiency
*Protein S deficiency
*Hyperhomocysteinemia
*[[Sickle cell crisis|Sickle cell anemia]] (S/S and S/beta thalassemia)<ref>Naik RP, et al. Venous thromboembolism in adults with sickle cell disease: A serious and under-recognized complication. ''Am J Med''. 2013;125(5):443-449.</ref>


==Workup by Probability==
===Evaluate bleeding risk (HAS-BLED)===
===Low Probability===
*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>
*Avoid CT pulmonary angiography in low probability patients that are either PERC rule negative or have a negative d-dimer
{| {{table}}
**Part of [[Choosing wisely ACEP|ACEP choosing wisely ]]
| align="center" style="background:#f0f0f0;"|'''Risk Factor'''
*If low prob and [[PERC Rule]] negative, then no workup
| align="center" style="background:#f0f0f0;"|'''Point'''
*If low prob and [[PERC Rule]] positive, then d-dimer
|-
*Age-adjusted D-Dimer in patients >50 yrs old (Age x 10 in FEU or Age x 5 in D-DU) has increased specificity without changing sensitivity<ref>Schouten, HJ, et al. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BJM. 2013; 346:f2492.</ref><ref>Adams, D, et al. Clinical utility of an age-adjusted D-dimer in the diagnosis of venous thromboembolism. Ann Emerg Med. 2014; 64:232-234.</ref>
| Hypertension||1
**Check your hospital's reference units (500 ng/L FEU = 250 ng/L D-DU)
|-
| 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).


===Moderate Probability===
===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>===
*D-dimer
*based on ACCP 2016 Guidelines
**However, it is unclear whether d-dimer alone is sufficient to rule-out PE<ref>ACEP Clinical Policy. http://www.acep.org/Content.aspx?id=80787 </ref>
{| 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
|-
|}


===High Probability===
==Diagnosis==
*Consider anticoagulation before imaging!
[[File:SaddlePE.png|thumb|A large pulmonary embolism at the bifurcation of the pulmonary artery (saddle embolism).]]
*CTA if GFR >60
===Definitive Diagnostic Imaging===
*V/Q if GFR <60
*CTA Chest if GFR >60
*V/Q scan if GFR <60
**Will be nondiagnostic if patient has effusion, pneumonia, or other airspace disease
**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%


===Bedside Ultrasound===
===Other Possible Diagnostic Findings===
*[[Ultrasound: Cardiac|Ultrasound]] can help diagnosis in equivocal cases
[[File:dsign.gif|thumb|D Sign<ref>http://www.thepocusatlas.com/right-ventricle</ref>]]
*Assess for right ventricular strain (RVS) and McConnell's sign
[[File:Hamptons.jpg|thumb|Hampton's Hump.]]
*RVS 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>
*[[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>
===Other Modalities===
***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  
*SPECT  
**Combination of noncontrast CT chest with V/Q scan
**Combination of non-contrast CT chest with V/Q scan
**Avoidance of contrast for patients with renal injury
**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>
**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>
Line 58: Line 139:
==Management==
==Management==
===Supportive care===
===Supportive care===
*Give [[IVF]] as necessary to increase preload while frequently assessing volume status
*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===
===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).
*Always consider [[Pulmonary_embolism#Evaluate_bleeding_risk_.28HAS-BLED.29|bleeding risk]] when determining risks/benefits of initiating anticoagulation
*The Feb. 2016 CHEST Guideline recommends clinical surveillance over anticoagultation for subsegmental PE with no proximal DVT at low risk for recurrent VTE based on [[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>
*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).
*'''[[LMWH]] SC'''
**1st line for most hemodynamically stable patients
**Contraindicated in renal failure
**Enoxaparin 1mg/kg SC q12h
**Dalteparin 200 IU/kg SC q24h, max 18,000 IU
*'''[[Unfractionated Heparin]]'''
**80 units/kg bolus; then 18 units/kg/hr
**Check PTT after 6hr; adjust infusion to maintain PTT at 1.5-2.5x control
**Benefit of Heparin is the short half life and easy ability to turn off the infusion.  Consider
**Patients with morbid obesity or anasarca may have poor  sc absorption with LMWH
**No need for renal dosing
**The prefered anticoagulation if thrombolysis is being considered or if there is a bleeding risk or trauma and anticoagulation will need to be emergently discontinued
**[[Dabigatran]]
*A direct thrombin inhibitor
**Approved by the FDA in 2014 for the treatment of DVT and PE
**Dabigatran was 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. </ref><ref>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>
*'''[[Rivaroxaban]]'''
**Factor Xa inhibitors
**Approved by the FDA in November 2012 for the treatment of DVT or PE
**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.</ref><ref>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>
*[[Apixaban]]
**Factor Xa inhibitor
**Approved for treatment of PE in August 2014
**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.</ref><ref>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>


===Thrombolysis===
{| {{table}}
*'''Major controversy exists regarding thrombolytic therapy in submassive PE. Therapy should be individualized to patients.'''<ref>Elliott C. et al. Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla.</ref><ref>Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPPETT trial). J Cardiol 2013; 111: 273-7</ref><ref>Meyer G. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014; 370(15): 1402-1411</ref> ''''The mortality benefit may be greatest in patients with right ventricular dysfunction.''' <ref>Chatterjee. S et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311(23):2414-21. PubMed ID: 24938564.</ref>
| 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
|}


*'''Bleeding risk is increased with increasing age especially in the group ≥ 65 yo'''<ref>[[Thrombolysis_in_Pulmonary_Embolism_Metanalysis*Outcomes]]</ref>
*Duration
**3-6 mo, if time limited risk factor (post-op, trauma, estrogen use)
**6 mo to life, if idiopathic etiology or recurrent


====Indications====
===Subsegmental PE===
*Patients with massive PE and acceptable risk of bleeding complications
*Evaluate for proximal DVT in legs with ultrasound
*Patient with submassive PE with evidence adverse prognosis + low risk of bleeding complications
**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>
**Hemodynamic instability
**If high risk for recurrent VTE: anticoagulation recommended over surveillance
**Worsening respiratory insufficiency
**Severe Right Ventricular dysfunction
**Major myocardial necrosis


====Thrombolytic Instructions====
===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>===
*Review contraindications
*Includes catheter-directed thrombolysis and mechanical thrombus removal without thrombolysis
*Discontinue heparin during infusion
*Still no large prospective cohort or randomized trial evaluating CDT, so limited evidence recommendations from ACCP 2016 are weak
*tPA 100mg over 2hr OR 0.6mg/kg over 2min
**Primary outcome measure in study of 59 patients was improved RV function at 24 hours, but not mortality
*After infusion complete measure PTT
*Given broad clinical spectrum of intermediate-risk PE, CDT can be considered in a subset of patients with following characteristics:
**Once value is <2x upper limit restart anticoagulation
**Intermediate-risk PE with more severe degree of RV dysfunction and positive biomarkers
 
**Intermediate-risk PE with severe hypoxemia
====Absolute contraindications====
**High-risk (massive) PE with contraindications to systemic thrombolysis
*Any prior intracranial hemorrhage,
*Complications include major access site bleeding, significant arrhythmias, pulmonary artery dissection, tamponade, worsening hemodynamics
*Known structural intracranial cerebrovascular disease (e.g. AVM)
*Known malignant intracranial neoplasm
*Ischemic stroke within 3mo
*Suspected aortic dissection
*Active bleeding or bleeding diathesis
*Recent surgery encroaching on the spinal canal or brain
*Recent closed-head or facial trauma with radiographic evidence of bony fracture or brain injury
 
====Relative contraindications====
*Age >75 years
*Current use of anticoagulation
*[[PE in Pregnancy]]
*Noncompressible vascular punctures
*Traumatic or prolonged CPR (>10min)
*Recent internal bleeding (within 2 to 4 weeks)
*History of chronic, severe, and poorly controlled hypertension
*Severe uncontrolled HTN on presentation (sys BP >180 or dia BP >110)
*Dementia
*Remote (>3 months) ischemic stroke
*Major surgery within 3 weeks


===Thrombolysis===
*See [[Thrombolysis for PE]]
===[[IVC Filter]]===
===[[IVC Filter]]===
*Indications
*Indications
Line 138: Line 250:
==Disposition==
==Disposition==
*Patients with significant clot burden generally require admission for anticoagulation
*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>
*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
|-
|}
<div style="display:none">
<!-- SMW MedicationDose annotations for PE anticoagulation -->
{{MedicationDose|drug=Enoxaparin|dose=1 mg/kg SC q12h|route=SC|context=Anticoagulation (1st line, LMWH)|indication=Pulmonary embolism|notes=Preferred in cancer, liver disease, coagulopathy, pregnancy}}
{{MedicationDose|drug=Unfractionated heparin|dose=80 units/kg IV bolus, then 18 units/kg/hr continuous infusion|route=IV drip|context=Anticoagulation (preferred if rapid reversal needed)|indication=Pulmonary embolism|display=Heparin (UFH)|notes=Short half-life; preferred if considering thrombolytics or bleeding risk}}
{{MedicationDose|drug=Rivaroxaban|dose=15 mg PO BID x3 weeks, then 20 mg PO daily|route=PO|context=Anticoagulation (DOAC)|indication=Pulmonary embolism|notes=Preferred if parenteral therapy to be avoided}}
{{MedicationDose|drug=Apixaban|dose=10 mg PO BID x1 week, then 5 mg PO BID|route=PO|context=Anticoagulation (DOAC)|indication=Pulmonary embolism}}
</div>
==See Also==
==See Also==
*[[Pulmonary Embolism in Pregnancy]]
*[[Pulmonary Embolism in Pregnancy]]
*[[IVC Filter]]
*[[IVC Filter]]
*[[Ultrasound: Cardiac]]
*[[Cardiac ultrasound]]
{{Thrombolysis Submassive PE Trials}}
{{Thrombolysis Submassive PE Trials}}
== Calculators ==
{{Aa Gradient Calculator}}
{{Wells_PE_Calculator}}
{{PERC_Calculator}}


==External Links==
==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/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/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/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==
==References==

Latest revision as of 22:40, 19 April 2026

See pulmonary embolism in pregnancy for pregnancy specific information.[1]

Background

Pulmonary embolism is an obstruction of one of the branches of the pulmonary arteries by material; typically a thrombus

  • Fat, Air, and tumor embolisms can similarly and obstruct a branch of the pulmonary artery, but are not covered in this section
  • A pulmonary embolism is on the spectrum of Venous thromboembolism (VTE)
  • Most emboli are thought to arise from lower extremity proximal veins (iliac, femoral, and popliteal), whereas a thrombus of the distal veins (calf) resolves spontaneously ⅔ of the time [2] [3] [4]
Pulmonary emboli can be classified according to the level along the pulmonary arterial tree.

Epidemiology

  • In the US, approximately 370,000-390,000 PE’s are diagnosed annually [5] [6]
  • Mortality
    • Hemodynamically stable (AHA/ACC Class A & B or ESC Low Risk) patients with a PE have a direct mortality of about 1%, however hemodynamically unstable patients mortality ranges from 25-50% [7]
    • For almost one quarter of PE patients, the initial clinical presentation is sudden death [8]

Clinical Features

DVT of right leg
  • Diagnosis of PE is challenging, with less than 10% of patients evaluated for a PE ultimately diagnosed with a PE [9]

Symptoms

Signs

  • Tachycardia (HR>100), Tachypnea (RR>20), Hypoxemia (SpO2<95%) are seen ~50% of the time
  • Hypotension (SBP<90) only seen 10% of the time, but largest predictor of mortality
  • Unilateral calf tenderness or edema, suggestive of a DVT
  • Other signs may include accentuated pulmonic component of second heart sound, JVD, or decreased breath sounds

Differential Diagnosis

Chest pain

Critical

Emergent

Nonemergent

Acute dyspnea

Emergent

Non-Emergent

Workup

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[10] (ACEP Level B)
  • Initial Wells study and prospective validation [11] 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[12]

Wells Criteria

Clinical Features Points
Symptoms of DVT (leg swelling and pain with palpation) 3.0
PE as likely as or more likely than an alternative diagnosis 3.0
HR >100 bpm 1.5
Immobilization for >3 consecutive days or surgery in the previous 4 weeks 1.5
Previous DVT or PE 1.5
Hemoptysis 1.0
Malignancy (receiving treatment, treatment stopped within 6 mon, palliative care) 1.0
Two Tier Wells Score
  • Score 0-4 = PE Unlikely (12.1% incidence of PE)
    • Check D-dimer
      • If D-dimer positive then obtain CTPA or V/Q scan
      • If D-dimer negative, no further workup needed (0.5% incidence of PE at 3 month follow up)
  • Score >4 = PE Likely (37.1% incidence of PE)
    • Obtain CT Pulmonary Angiography or V/Q Scan
  • New evidence suggests lower Wells Score with D-dimer <1000 ng/mL is effective at ruling out PE without imaging

Low-Probability Testing in the ED

  • PERC Rule negative, then no further workup[10] (ACEP Level B)
    • Avoid CT pulmonary angiography in low pretest probability patients that are either PERC rule negative or have a negative d-dimer (ACEP choosing wisely)
    • D-dimer NPV is 99.5%[13]
  • PERC Rule positive, then D-dimer (see Moderate-Probability Testing below)[10] (ACEP Level B)
    • Can also consider using Wells score as above to determine further testing

Adjusted D-Dimer to Higher Threshold

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
  • Sickle cell anemia (S/S and S/beta thalassemia)[15]

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[16]
Risk Factor 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[17]

  • based on ACCP 2016 Guidelines
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

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[10] (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

D Sign[18]
Hampton's Hump.
  • ECG (abnormal in 70% of PE [19] and associated with an adverse prognosis[20])
    • T-wave inversions (34%)[21]
      • Anterior/septal leads (V1-V4) and inferior leads[22]
    • 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) [23]
    • 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[24]
  • Formal transthoracic echo or 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[25]
    • 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[26]
  • 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[27]

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[28]
    • 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[29]

Anticoagulation

  • Always consider 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).
Name LMWH SC Unfractionated Heparin Dabigatran Rivaroxaban Apixaban Coumadin
Initial Dose
  • 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 [30]
  • 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 [31]
  • 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 [32]
  • 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 (Level 2C evidence)[33]
    • If high risk for recurrent VTE: anticoagulation recommended over surveillance

Catheter-directed Therapy for intermediate-risk (submassive) PE[34]

  • 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

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 [35]
  • Risk stratify which patients can be discharged using HESTIA[36], sPESI, or PESI scores[37].

Prognosis

The Pulmonary Embolism Severity Index (PESI)[38]

  • PE patients with PESI class I or II seem safe to manage as outpatients.
Prognosis Variable 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
Risk Class 30-Day Mortality 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


Enoxaparin 1 mg/kg SC q12h SC — Preferred in cancer, liver disease, coagulopathy, pregnancy Heparin (UFH) 80 units/kg IV bolus, then 18 units/kg/hr continuous infusion IV drip — Short half-life; preferred if considering thrombolytics or bleeding risk Rivaroxaban 15 mg PO BID x3 weeks, then 20 mg PO daily PO — Preferred if parenteral therapy to be avoided Apixaban 10 mg PO BID x1 week, then 5 mg PO BID PO

See Also

Thrombolytics for pulmonary embolism

Calculators

A-a O₂ Gradient

Alveolar-arterial (A-a) O₂ Gradient
Parameter Value
Age (years)
FiO₂ (%)
PaCO₂ (mmHg)
PaO₂ (mmHg)
A-a Gradient mmHg
Expected A-a mmHg (age-adjusted normal)
Interpretation
  • Normal A-a gradient ≈ (Age/4) + 4 on room air
  • Elevated A-a gradient suggests: V/Q mismatch, shunt, or diffusion impairment
  • Normal A-a gradient + hypoxia suggests: hypoventilation or low FiO₂
References
  • Formula: A-a = [FiO₂ × (Patm – PH2O)] – (PaCO₂/0.8) – PaO₂
  • Kanber GJ, et al. The alveolar-arterial oxygen gradient in young and elderly men during air and oxygen breathing. Am Rev Respir Dis. 1968;97(3):376-381. PMID 5637791.

Wells Score for PE

Wells' PE Score Calculator
Criteria No Yes Points
Clinical signs and symptoms of DVT (leg swelling, pain with palpation) 1 +3.0
PE is #1 diagnosis OR equally likely 1 +3.0
Heart rate >100 bpm 1 +1.5
Immobilization (≥3 days) OR surgery in previous 4 weeks 1 +1.5
Previous objectively diagnosed PE or DVT 1 +1.5
Hemoptysis 1 +1.0
Malignancy (treatment within 6 months or palliative) 1 +1.0
Wells' Score points
Three-Tier Model
0–1 Low Risk — 1.3% incidence of PE. Consider D-dimer to rule out. Consider PERC rule.
2–6 Moderate Risk — 16.2% incidence of PE. Consider high-sensitivity D-dimer or CTA.
>6 High Risk — 37.5% incidence of PE. Consider CTA. D-dimer not recommended.
Two-Tier Model (Preferred by guidelines)
0–4 PE Unlikely — 12.1% incidence. Consider high-sensitivity D-dimer; if negative, stop workup.
>4 PE Likely — 37.1% incidence. Consider CTA testing.
References
  • Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism. Thromb Haemost. 2000;83(3):416-420. PMID 10744147.
  • van Belle A, Büller HR, Huisman MV, 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. PMID 16403929.

PERC Rule

PERC Rule Calculator
Criteria No (0) Yes (+1)
Age ≥50 years 1
Heart rate ≥100 bpm 1
SpO₂ <95% on room air 1
Unilateral leg swelling 1
Hemoptysis 1
Recent surgery or trauma (within 4 weeks requiring hospitalization) 1
Prior PE or DVT 1
Hormone use (oral contraceptives, HRT, or estrogenic hormones) 1
Positive Criteria / 8
Interpretation
Score = 0 PERC Negative — If pre-test probability is ≤15%, PE is effectively ruled out. No further workup needed (sensitivity 97.4%, NPV 99.5%).
Score ≥ 1 PERC Positive — Cannot rule out PE by PERC alone. Consider D-dimer, Wells' score, or CTA based on clinical suspicion.

External Links

References

  1. ↑ 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
  2. ↑ Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I22-I30. doi:10.1161/01.CIR.0000078464.82671.78
  3. ↑ Lautz TB, Abbas F, Walsh SJ, et al. Isolated gastrocnemius and soleal vein thrombosis: should these patients receive therapeutic anticoagulation?. Ann Surg. 2010;251(4):735-742. doi:10.1097/SLA.0b013e3181c1ae95
  4. ↑ Macdonald PS, Kahn SR, Miller N, Obrand D. Short-term natural history of isolated gastrocnemius and soleal vein thrombosis. J Vasc Surg. 2003;37(3):523-527. doi:10.1067/mva.2003.149
  5. ↑ Freund Y, Cohen-Aubart F, Bloom B. Acute Pulmonary Embolism: A Review. JAMA. 2022;328(13):1336-1345. doi:10.1001/jama.2022.16815
  6. ↑ Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023;147(8):e93-e621. doi:10.1161/CIR.0000000000001123
  7. ↑ Schultz J, Giordano N, Zheng H, et al. EXPRESS: A Multidisciplinary Pulmonary Embolism Response Team (PERT) - Experience from a national multicenter consortium. Pulm Circ. Published online January 11, 2019. doi:10.1177/2045894018824563
  8. ↑ Walls R, Hockberger R, Gausche-Hill M, Erickson TB, & Wilcox SR. (2022). Rosen's Emergency Medicine - Concepts and Clinical Practice E-Book (10th ed.). Elsevier - OHCE.
  9. ↑ Creager MA, Barnes GD, et al. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. Published online February 19, 2026. doi:10.1161/CIR.0000000000001415
  10. ↑ 10.0 10.1 10.2 10.3 ACEP Clinical Policy for Pulmonary Embolism full text
  11. ↑ 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
  12. ↑ 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
  13. ↑ 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
  14. ↑ Flex your D-dimer Taming of the SRU http://www.tamingthesru.com/blog/diagnostics/flex-your-d-dimer
  15. ↑ Naik RP, et al. Venous thromboembolism in adults with sickle cell disease: A serious and under-recognized complication. Am J Med. 2013;125(5):443-449.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ http://www.thepocusatlas.com/right-ventricle
  19. ↑ 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.
  20. ↑ 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
  21. ↑ 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.
  22. ↑ 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
  23. ↑ 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
  24. ↑ 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. full text
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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
  28. ↑ Mercat A et al. Hemodynamic effects of fluid loading in acute massive pulmonary embolism. Crit Care Med. 1999 Mar;27(3):540-4
  29. ↑ 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
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ Kearon, Clive, et al. "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report." Chest (2016).[fulltext]
  34. ↑ 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
  35. ↑ 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.
  36. ↑ Zondag et al. Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism. European Respiratory Journal. 2013; 41:588-592.
  37. ↑ 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
  38. ↑ 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.
Retrieved from "https://www.wikem.org/w/index.php?title=Pulmonary_embolism&oldid=390057"