Pulmonary embolism treatment approach: Difference between revisions

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__NOTOC__
'''To go back to the wikidoc page on [[VTE]], click [[Venous thromboembolism|click here]]'''
{| class="infobox" style="float:right;"
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| [[File:Siren.gif|30px|link=Pulmonary embolism resident survival guide]]|| <br> || <br>
| [[Pulmonary embolism resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
{{Pulmonary embolism}}
{{Pulmonary embolism}}
'''Editor(s)-In-Chief:''' {{ATI}}, [[C. Michael Gibson, M.S., M.D.]] [mailto:mgibson@perfuse.org]; '''Associate Editor(s)-In-Chief:''' [[Kashish Goel|Kashish Goel, M.D.]]; [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; {{CZ}}
'''Editor(s)-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], {{ATI}}; '''Associate Editor(s)-In-Chief:''' [[Kashish Goel|Kashish Goel, M.D.]]; {{Rim}}
 
'''This page provides algorithms about the treatment choices.  For more details about the medical therapy, click [[pulmonary embolism medical therapy|here]].  For more details about embolectomy, click [[pulmonary embolism embolectomy|here]].'''


==Overview==
==Overview==
'''Pulmonary embolism''' (PE) is a potentially lethal condition, with a mortality rate close to 30 percent without treatment. Thus, prompt therapy is of utmost important. In most cases, [[anticoagulant]] therapy is the mainstay of treatment. A proposed treatment algorithm is presented at the end of this chapter.
Prompt recognition, diagnosis and treatment of pulmonary embolism is critical. [[Anticoagulant]] therapy is the mainstay of treatment for patients who are [[hemodynamically]] stable. If [[hemodynamic ]]compromise is present, then [[fibrinolytic]] therapy is recommended.


==Risk stratification==
==Step 1: Confirm PE==
One of the most important aspects in the care of a patient with acute PE is triage or early risk stratification.
Shown below is an algorithm depicting the initial diagnostic approach to pulmonary embolism.<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref><ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>
* [[Pulmonary embolism classification scheme#Low-risk Pulmonary Embolism|Low-risk PE]]: Therapeutic [[anticoagulation]], unless contraindicated.
* [[Pulmonary embolism classification scheme#Submassive Pulmonary Embolism|Submassive PE]]: If the patient is hemodynamically stable without major [[RV dysfuncti]][[ or infarction, therapeutic anticoagulation should be started. In some cases, [[thrombolysis]] may be indicated.
* [[Pulmonary embolism classification scheme#Massive Pulmonary Embolism|Massive PE]]: Thrombolysis is indicated and ICU admission may be required. Initial supportive therapies in these patients may include:
** Respiratory support with oxygen for [[Hypoxemia|hypoxemic]] patients or mechanical [[ventilation]] in cases of severe [[Hypoxemia|hypoxemia]] or [[respiratory failure]].
** Hemodynamic support with intravenous fluids or intravenous vasopressors for [[hypotensive]] patients. Intravenous fluids should be administered cautiously, as increased right ventricular load can disable the right ventricular oxygen supply-to-demand balance.<ref name="pmid10199533">{{cite journal |author=Mercat A, Diehl JL, Meyer G, Teboul JL, Sors H |title=Hemodynamic effects of fluid loading in acute massive pulmonary embolism |journal=Crit. Care Med. |volume=27 |issue=3 |pages=540–4 |year=1999 |month=March |pmid=10199533|doi=|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=27&issue=3&spage=540|accessdate=2011-12-12}}</ref>


* If anticoagulation is contraindicated, an [[IVC filter]] is recommended.
{{familytree/start}}
{{familytree | | | | | | | | | | | | | | | | A00 | | | | | A00= '''Does the patient who is suspected to have PE have [[hypotension]] or [[shock]]?'''}}
{{familytree | | | | | | | |,|-|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|-|-|.| }}
{{familytree | | | | | | | A01 | | | | | | | | | | | | | | | | | A02 |  A01= Yes| A02= No}}
{{familytree | | | | | | | |!| | | | | | | | | | | | | | | | | | |!| }}
{{familytree | | | | | | | A02 | | | | | | | | | | | | | | | | | A03 |  A02= '''Suspected high-risk PE'''| A03= '''Suspected non-high risk PE'''}}
{{familytree | | | | | | | |!| | | | | | | | | | | | | | | | | | |!| }}
{{familytree | | | | | | | A04 | | | | | | | | | | | | | | | | | |!| A04= ''Administer [[anticoagulation]]'' <br>''(in case there are no contraindications)''<br>''during the diagnostic workup''}}
{{familytree | | | | | | | |!| | | | | | | | | | | | | | | | | | |!| }}
{{familytree | | | | | | | B01 | | | | | | | | | | | | | | | | | B02| B01= '''Is a [[CT]] available immediately?'''| B02= '''What is the pretest probability of PE?''' <br> Assess the pretest probability of PE<br> by using one of the risk score:<br> - [[Wells score]] <br> - [[Geneva score]] <br> - [[PERC]]}}
{{familytree | | | |,|-|-|-|^|-|-|-|-|-|-|-|.| | | | | | |,|-|v|-|^|-|-|.| | }}
{{familytree | | | C01 | | | | | | | | | | C02 | | | | | |!| |!| | | | |!| | C01= No| C02= Yes}}
{{familytree | | | |!| | | | | | | | | | | |!| | | | | | |!| |!| | | | |!| | }}
{{familytree | | | D01 | | | | | | | | | | |!| | | | | | |!| |!| | | | |!| | D01= '''Order [[echocardiography]]'''}}
{{familytree | | | |!| | | | | | | | | | | |!| | | | | | |!| |!| | | | |!| | }}
{{familytree | | | E01 | | | | | | | | | | |!| | | | | E02 | | E03 | | E04 |  E01= '''Does the patient have [[RV]] overload?'''| E02= '''Low pretest probability''' |E03= '''Intermediate pretest probability'''| E04= '''High pretest probability''' <br>OR<br> '''PE is likely'''}}
{{familytree | | | |!| | | | | | | | | | | |!| | | | | | |!| |!| | | | |!| }}
{{familytree | | | |!| | | | | | | | | | | |!| | | | | | |!| | N01 | | N02 | N01= ''Administer [[anticoagulation]]'' <br>''(in case there are no contraindications)''<br>''during the diagnostic workup''|N02= ''Administer [[anticoagulation]]'' <br>''(in case there are no contraindications)''<br>''during the diagnostic workup''}}
{{familytree | |,|-|^|-|-|-|.| | | | | | | |!| | | | | | |!| |!| | | | |!| | }}
{{familytree | F01 | | | | F02 | | | | | | F03 | | | | | | F04 | | | | |!| F01= No| F02= Yes| F03= '''Order [[CT]]'''| F04= '''Order [[D-dimer]]'''}}
{{familytree | |!| | | | | |!| | | | | |,|-|^|-|.| | | |,|-|^|-|.| | | |!| }}
{{familytree | |!| | | | | |!| | | | | G02 | | G03 | | G04 | | G05 | | |!| G01= | G02= Positive| G03= Negative| G04= Positive| G05= Negative}}
{{familytree | |!| | | |,|-|^|-|.| | | |!| | | |!| | | |!| | | |!| | | |!| }}
{{familytree | |!| | | H01 | | H02 | | |!| | | |!| | | H03 | | H04 | | H05 | | | H01= Is the patient unstable <br> OR<br> no other tests are available?| H02=Is the patient stabilized <br> AND <br> CT is now available?| H03= '''Order CT'''| H04= PE is excluded| H05= '''Order [[CT]]'''}}
{{familytree | |!| | | |!| | | |!| | | |!| | | |!| | | |)|-|-|-|.| | | |)|-|-|-|.| | }}
{{familytree | |!| | | |!| | | |!| | | |!| | | |!| | | L01 | | L02 | | L03 | | L04 | L01= Positive| L02= Negative| L03= Positive| L04= Negative}}
{{familytree | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | }}
{{familytree | I01 | | I02 | | I03 | | I04 | | I05 | | I06 | | I07 | | I08 | | I09 | I01= PE is excluded| I02= Consider [[thrombolytic therapy]] or [[embolectomy]]| I03= Order CT| I04= PE is confirmed| I05=PE is excluded| I06= PE is confirmed| I07= PE is excluded| I08= PE is confirmed| I09= PE is excluded}}
{{familytree | | | | | | | |,|-|^|-|.| | | | }}
{{familytree | | | | | | | J01 | | J02 | | | J01= Positive for PE| J02= Negative for PE}}
{{familytree | | | | | | | |!| | | |!| | | | }}
{{familytree | | | | | | | K01 | | K02 | | | K01= PE is confirmed| K02= PE is excluded}}
{{familytree/end}}


==Initial treatment==
==Step 2: Initial Treatment==
===Anticoagulation===
Shown below is an algorithm depicting the initial management of pulmonary embolism.<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref><ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>
Most common reason for mortality is recurrent PE, occurring within the few hours of the initial event<ref name="pmid1560799">{{cite journal |author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins TE |title=The clinical course of pulmonary embolism|journal=N. Engl. J. Med. |volume=326 |issue=19 |pages=1240–5 |year=1992 |month=May |pmid=1560799|doi=10.1056/NEJM199205073261902|url=http://dx.doi.org/10.1056/NEJM199205073261902 |accessdate=2011-12-12}}</ref>. Anticoagulation is the cornerstone of therapy in acute [[pulmonary embolism]]<ref name="pmid1560799">{{cite journal |author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins TE |title=The clinical course of pulmonary embolism|journal=N. Engl. J. Med. |volume=326 |issue=19 |pages=1240–5 |year=1992 |month=May |pmid=1560799|doi=10.1056/NEJM199205073261902|url=http://dx.doi.org/10.1056/NEJM199205073261902 |accessdate=2011-12-12}}</ref><ref name="pmid10227218">{{cite journal |author=Goldhaber SZ, Visani L, De Rosa M|title=Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) |journal=Lancet |volume=353|issue=9162|pages=1386–9 |year=1999 |month=April |pmid=10227218 |doi=|url=http://linkinghub.elsevier.com/retrieve/pii/S0140673698075345|accessdate=2011-12-12}}</ref>. After initial risk stratification, immediate treatment should be started based on the following points<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref><ref name="pmid21422387">{{cite journal |author=Jaff MR, McMurtry MS, Archer SL, ''et al.'' |title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association |journal=Circulation |volume=123 |issue=16 |pages=1788–830 |year=2011 |month=April |pmid=21422387 |doi=10.1161/CIR.0b013e318214914f |url=}}</ref><ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, ''et al.'' |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29 |issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310 |url=}}</ref>:
{{familytree/start}}
* Initial treatment with parenteral anticoagulants including subcutaneous [[low molecular weight heparin|Low molecular weight heparin]](such as [[enoxaparin]] and [[dalteparin]]), subcutaneous [[Fondaparinux]] or intravenous [[unfractionated heparin]], unless contraindicated.
* [[ACCP guidelines]]<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommend [[low molecular weight heparin]] or [[fondaparinux]] over intravenous [[unfractionated heparin]].
* Anticoagulation should be started while awaiting confirmation tests, if there is moderate-to-high clinical suspicion of PE.
* [[Vitamin K antagonists]] like warfarin should be started the same day and parenteral anticoagulation should be continued for at least 5 days and preferably, until INR in 2.0 or above for 1-2 days.
* In patients with suspected or confirmed [[heparin-induced thrombocytopenia]], [[lepirudin]] or [[argatroban]] should be used.


{{familytree | | | | | | | | | | | A01 | | | | | | | | | | | | A01= '''Assess the severity of pulmonary embolism'''}}
{{familytree | | | |,|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|.| | | | | }}
{{familytree | | | B01 | | | | | | B02 | | | | | | B03 | | | | B01= '''Massive PE''' <br> ''(also known as high-risk PE)'' <br> [[Cardiogenic shock]] <br> OR<br> Persistent [[hypotension]] (≤90mmHg)<br> OR<br> Drop of the [[blood pressure]] by ≥ 40mmHg for > 15 min<ref name="pmid16009801">{{cite journal| author=Kucher N, Goldhaber SZ| title=Management of massive pulmonary embolism. | journal=Circulation | year= 2005 | volume= 112 | issue= 2 | pages= e28-32 | pmid=16009801 | doi=10.1161/CIRCULATIONAHA.105.551374 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16009801  }} </ref><br> OR <br> [[Pulselessness]] <br> OR<br> Profound bradycardia (<40 bpm) with findings of shock<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>| B02= '''Submassive PE''' <br> ''(also know as intermediate-risk PE)'' <br> Right ventricular dysfunction <br> AND/OR <br> Myocardial injury (Troponin +)| B03= '''Low-risk PE''' <br> No [[cardiogenic shock]] <br> AND <br> No hypotension <br> AND <br> No right ventricular dysfunction <br> AND <br> No myocardial injury (Troponin -)}}
{{familytree | | | |!| | | | | | | |!| | | | | | | |!| | | | | }}
{{familytree | | | B04 | | | | | | |!| | | | | | | |!| | | | | B04= '''Provide hemodynamic and respiratory support''' <br>
Begin high dose unfractionated heparin
<ref name="pmid16009801">{{cite journal| author=Kucher N, Goldhaber SZ| title=Management of massive pulmonary embolism. | journal=Circulation | year= 2005 | volume= 112 | issue= 2 | pages= e28-32 | pmid=16009801 | doi=10.1161/CIRCULATIONAHA.105.551374 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16009801  }} </ref>: Bolus 10.000 U
: Continuous infusion of at least 1250 U/hour for a targeted [[apTT]] of at least 80 s
Administer rapidly 500-1000 mL of normal saline (Caution with fluid overload)<ref name="pmid16009801">{{cite journal| author=Kucher N, Goldhaber SZ| title=Management of massive pulmonary embolism. | journal=Circulation | year= 2005 | volume= 112 | issue= 2 | pages= e28-32 | pmid=16009801 | doi=10.1161/CIRCULATIONAHA.105.551374 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16009801  }} </ref><br>
Have a low threshold for ionotropes (dopamine or dobutamine)<ref name="pmid16009801">{{cite journal| author=Kucher N, Goldhaber SZ| title=Management of massive pulmonary embolism. | journal=Circulation | year= 2005 | volume= 112 | issue= 2 | pages= e28-32 | pmid=16009801 | doi=10.1161/CIRCULATIONAHA.105.551374 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16009801  }} </ref><br>
Administer oxygen for hypoxemic patients<ref name="pmid16009801">{{cite journal| author=Kucher N, Goldhaber SZ| title=Management of massive pulmonary embolism. | journal=Circulation | year= 2005 | volume= 112 | issue= 2 | pages= e28-32 | pmid=16009801 | doi=10.1161/CIRCULATIONAHA.105.551374 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16009801  }} </ref><br>}}
{{familytree | | | |!| | | | | | | |!| | | | | | | |!| | | | | }}
{{familytree | | | C01 | | | | | | C02 | | | | | | C03 | | | | C01= '''Is there any contraindication for fibrinolytic therapy?'''| C02= '''Is there any contraindication for anticoagulation therapy?'''| C03= '''Is there any contraindication for anticoagulation therapy?'''}}
{{familytree | |,|-|^|-|.| | | |,|-|^|-|.| | | |,|-|^|-|.| | | }}
{{familytree | D01 | | D02 | | D03 | | D04 | | D05 | | D06 | | D01= NO| D02= YES| D03= NO|D04= YES| D05= NO| D06= YES}}
{{familytree | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | }}
{{familytree | E01 | | E02 | | E03 | | E04 | | E05 | | E06 | | E01= Discontinue unfractionated heparin <br> AND <br> Begin fibrinolytic therapy| E02= Surgical pulmonary embolectomy <br> OR <br> Percutaneous catheter embolectomy| E03= Anticoagulation therapy <br> AND <br> Hospital admission|E04= IVC filter <br> AND <br>Hospital admission| E05= Anticoagulation therapy<br> AND <br> Early discharge/home treatment| E06= IVC filter <br> AND <br> Early discharge/home treatment}}
{{familytree | |!| | | | | | | | |!| |!| | | | }}
{{familytree | F01 | | | | | | | | F02 | | | | F01= '''Does the patient fail to improve''' <br> OR <br> '''Develop [[cardiogenic shock]]?'''<br> OR <br> '''Develop [[hypotension]]?'''| F02= '''Does the patient fail to improve''' <br> OR <br> '''Develop [[cardiogenic shock]]?'''<br> OR <br> '''Develop [[hypotension]] (<90 mmHg)?''' <br> OR <br> '''Develop respiratory distress (SaO2<95% with Borg score>8 or altered mental status)''' <br> OR <br> '''Have moderate to severe RV dysfunction (RV hypokinesis or estimated RVSP>40 mmHg)''' <br> OR <br> '''Elevated biomarkers (troponin> upper limit of normal, BNP>100 pg/mL, or pro-BNP>900 pg/mL)'''<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>}}
{{familytree |,|^|-|-|-|.| | | |,|-|^|-|.| | | | }}
{{familytree | F03 | | F04 | | F05 | | F06 | | | F03= YES| F04= NO| F05= YES| F06= NO}}
{{familytree | |!| | | |!| | | |!| | | |!| }}
{{familytree | G01 | | G02 | | G03 | | G04 | | G01= Surgical pulmonary embolectomy <br> OR <br> Percutaneous catheter embolectomy|G02= Continue with the same treatment| G03= '''Is there any contraindication for fibrinolytic therapy?'''| G04= Continue with the same treatment}}
{{familytree | | | | | | | |,|-|^|-|.| | | }}
{{familytree | | | | | | | H01 | | H02 | | H01= NO| H02= YES}}
{{familytree | | | | | | | |!| | | |!| | | | }}
{{familytree | | | | | | | I01 | | I02 | | I01=Hold anticoagulation and give thrombolytics| I02= Surgical pulmonary embolectomy <br> OR <br> Percutaneous catheter embolectomy}}
{{familytree | | | | | | | |!| | | }}
{{familytree | | | | | | | J01 | | J01= '''Does the patient fail to improve?''' }}
{{familytree | | | | | |,|-|^|-|.| }}
{{familytree | | | | | K01 | | K02 | K01= YES | K02= NO }}
{{familytree | | | | | |!| | | |!| | | }}
{{familytree | | | | | L01 | | L02 | L01= Surgical pulmonary embolectomy <br> OR <br> Percutaneous catheter embolectomy| L02= Continue with the same treatment}}
{{familytree/end}}


* Other salient features:
===Initial Anticoagulation Therapy===
**Prevents further clot formation, so should be started as early as possible.
{{Family tree/start}}
**It has no effect on pre-existing clot lysis.
{{familytree | | | | A01 | | | | | | A01= <div style="float: left; text-align: left; width: 15em; padding:1em;">'''Begin initial [[anticoagulation therapy]] in:''' <br> ❑ '''Confirmed PE''' <br>OR <br> ❑ '''High or intermediate probability of PE while awaiting the diagnostic tests''' </div>}}
**It has no effect in decreasing the size of thrombus.
{{familytree | | | | |!| | | | | | | }}
**Warfarin therapy often requires frequent dose adjustment and monitoring of the [[international normalized ratio|INR]]. In PE, INRs between 2.0 and 3.0 are generally considered ideal.  
{{familytree | | | | B01 | | | | | | B01= <div style="float: left; text-align: left; width: 15em; padding:1em;">'''Is the patient high risk or non-high risk?''' </div>}}
**Anticoagulation should be used with caution, because certain conditions like [[pericardial tamponade]] and [[aortic dissection]] can mimic [[pulmonary embolism]], but the use of anticoagulants is contraindicated in these medical conditions.
{{familytree | |,|-|-|^|-|-|.| | | | }}
{{familytree | C01 | | | | C02 | | | C01= '''[[Pulmonary embolism classification#Massive Pulmonary Embolism|High risk]]'''| C02= '''[[Pulmonary embolism classification|Non-high risk]]'''}}
{{familytree | |!| | | | | |!| | | | }}
{{familytree | D01 | | | | D02 | | | D01=
<div style="float: left; text-align: left; width: 15em; padding:1em;">❑ Administer IV [[unfractionated heparin]]<ref name="pmid22315259">{{cite journal| author=Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al.| title=Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e152S-84S | pmid=22315259 | doi=10.1378/chest.11-2295 | pmc=PMC3278055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315259  }} </ref>
</div>| D02= <div style="float: left; text-align: left; width: 15em; padding:1em;">'''Does the patient have:''' <br> ❑ '''High risk of [[bleeding]]''' <br> OR <br> ❑ '''Severe [[renal failure]]?''' </div>}}
{{familytree | | | | | |,|-|^|-|.| | }}
{{familytree | | | | | E01 | | E02 | E01= '''Yes'''| E02= '''No'''}}
{{familytree | | | | | |!| | | |!| | }}
{{familytree | | | | | F01 | | F02 | F01= <div style="float: left; text-align: left; width: 15em; padding:1em;">❑ Administer [[unfractionated heparin]]:<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref>
:❑ IV injection<br> OR<br>
:❑ SC injection</div>| F02= <div style="float: left; text-align: left; width: 15em; padding:1em;">❑ Administer ONE of the following:<ref name="pmid22315259">{{cite journal| author=Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al.| title=Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e152S-84S | pmid=22315259 | doi=10.1378/chest.11-2295 | pmc=PMC3278055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315259  }} </ref>
:❑ SC [[low molecular weight heparin]] (1st line)
:❑ SC [[fondaparinux]] (1st line)
:❑ IV [[unfractionated heparin]]
:❑ SC [[unfractionated heparin]]
</div>}}
{{familytree/end}}


===[[Pulmonary embolism treatment thrombolysis|Thrombolysis]]===
==Step 3: Long Term Anticoagulation Therapy==
* [[Pulmonary embolism treatment thrombolysis|Thrombolysis]] is indicated in patients with a [[massive PE]] or those with a [[submassive PE]] who develop or are at risk of developing hypotension (SBP < 90 mmHg), unless contraindicated.
The long term management of [[PE]] depends on whether the episode is the first one or not, whether it is provoked or unprovoked, and on the risk of bleeding of the patient.  Among non cancer patients, the first line therapy for long term management of [[PE]] is [[vitamin K antagonist]]s (VKA); whereas the first line treatment among cancer patients is [[low molecular weight heparin]]. '''If long term treatment with VKA is decided, VKA should be started at the same day with heparin allowing for at least 5 days of overlap until the [[INR]] is ≥2 for at least 24 hours'''.  Among patients on extended [[anticoagulation therapy]], the risk vs benefits of the [[anticoagulation therapy]] should be assessed regularly (for example annually).<ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>
* Administration of a fibrinolytic is recommended via a peripheral intravenous catheter.
* FDA recommends infusion dose of [[alteplase]] 100 mg as a continuous infusion over 2 hours, supported by [[AHA]]<ref name="pmid21422387">{{cite journal |author=Jaff MR, McMurtry MS, Archer SL, ''et al.'' |title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association |journal=Circulation |volume=123 |issue=16 |pages=1788–830 |year=2011 |month=April |pmid=21422387 |doi=10.1161/CIR.0b013e318214914f |url=}}</ref> and [[ACCP]] guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>. 
* Withhold anticoagulation during these 2 hours of fibrinolytic infusion.
* The role of thrombolysis in [[submassive PE]] in not established at this point<ref>Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. ''Cochrane Database Syst Rev'' 2006;(2):CD004437. PMID 16625603.</ref>. Two ongoing trials are investigating this. 
* No large clinical trial has demonstrated mortality benefit of thrombolytic therapy. However, it helps by accelerating clot lysis, improving pulmonary perfusion and right ventricular function<ref name="pmid12374874">{{cite journal |author=Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W |title=Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism |journal=N. Engl. J. Med. |volume=347 |issue=15 |pages=1143–50 |year=2002|month=October|pmid=12374874|doi=10.1056/NEJMoa021274 |url=http://dx.doi.org/10.1056/NEJMoa021274 |accessdate=2011-12-13}}</ref><ref name="pmid2123152">{{cite journal |author=Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, Gent M |title=A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism |journal=Chest |volume=98 |issue=6 |pages=1473–9 |year=1990 |month=December|pmid=2123152|doi=|url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=2123152 |accessdate=2011-12-21}}</ref>


To read more about dosage, contraindications and guidelines, click [[Pulmonary embolism treatment thrombolysis|'''here''']].
{{Family tree/start}}
 
{{familytree | | | | | | | | | | A01 | | | | | | | | A01= '''Is this the first episode of PE?'''}}
===[[Pulmonary embolism#Surgery:|Surgical procedures]]===
{{familytree | | | | | |,|-|-|-|-|^|-|-|-|-|.| | | | }}
* [[Pulmonary thrombectomy|Catheter-assisted thrombus removal]] is recommended in patients with [[massive PE]], who have contraindications or failed thrombolysis, or are in shock that will cause death before thrombolysis takes effect (hours).
{{familytree | | | | | B01 | | | | | | | | B02 | | | B01= '''YES'''| B02= '''NO'''}}
* [[Pulmonary thrombectomy|Pulmonary embolectomy]] is recommended if a patient with above conditions fails catheter-assisted embolectomy.
{{familytree | | | | | |!| | | | | | | | | |!| | | | }}
 
{{familytree | | | | | C01 | | | | | | | | C02 | | | C01= '''Is PE provoked?'''| C02= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|What is the risk of bleeding?]]'''}}
===[[IVC filter]]===
{{familytree | |,|-|-|-|+|-|-|-|.| | | |,|-|^|-|.| | }}
* [[IVC filter]] is indicated in whom anticoagulation is contraindicated.
{{familytree | D01 | | D02 | | D03 | | D04 | | D05 | | D01= '''Yes, transient reversible risk factor'''| D02= '''Yes, [[cancer]]'''| D03= '''No (unprovoked)'''| D04= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|Low or moderate]]'''| D05= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|High]]'''}}
* Anticoagulation should be restarted, once the contraindication is resolved.
{{familytree | |!| | | |!| | | |!| | | |!| | | |!| | }}
 
{{familytree | E01 | | E02 | | E03 | | E04 | | E05 | | E01= '''Therapy for 3 months'''<br><div style="float: left; text-align: left; padding:1em;">❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E02= '''Extended therapy or until cancer is cured'''<br><div style="float: left; text-align: left; padding:1em;">❑ [[LMWH]] (first line)<br> OR <br> ❑ [[VKA]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E03= '''Therapy for ≥ 3 months'''<br><div style="float: left; text-align: left; padding:1em;">❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E04= '''Extended therapy'''<br><div style="float: left; text-align: left; padding:1em;">❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E05= '''Therapy for 3 months'''<br><div style="float: left; text-align: left; padding:1em;">❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>}}
==Long-term treatment==
{{familytree | | | | | | | | | |!| | | | | | | | | | }}
* After initial treatment in the hospital, patient should continue anticoagulation for 3 months for a PE provoked by surgery or nonsurgical transient risk factor.
{{familytree | | | | | | | | | F01 | | | | | | | | | F01= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|Re-assess the risk of bleeding]]'''}}
* For an unprovoked PE, patient's risk should be re-evaluated at 3 months to be considered for extended therapy.
{{familytree | | | | | | | |,|-|^|-|.| | | | | | | | }}
* An abnormal [[D-dimer]] level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked pulmonary embolus.<ref name="pmid17065639">{{cite journal |author=Palareti G, Cosmi B, Legnani C, ''et al'' |title=D-dimer testing to determine the duration of anticoagulation therapy |journal=N. Engl. J. Med. |volume=355 |issue=17 |pages=1780-9 |year=2006 |pmid=17065639 |doi=10.1056/NEJMoa054444}}</ref>
{{familytree | | | | | | | G01 | | G02 | | | | | | | G01= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|Low or moderate]]'''| G02= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|High]]'''}}
 
{{familytree | | | | | | | |!| | | |!| | | | | | | | }}
* Long-term treatment is usually recommended with vitamin K antagonists like [[warfarin]], unless contraindicated or some special circumstances.
{{familytree | | | | | | | H01 | | H02 | | | | | | | H01= '''Extended therapy'''| H02= '''Do not extend the therapy beyond the initial 3 months'''}}
* Warfarin administration needs close monitoring as an outpatient and patient should have an appointment with "anticoagulation clinic" before leaving the hospital.
 
===Extended anticoagulation===
'Extended treatment''' should be considered in patients with:
# Active Cancer.
# Unprovoked Pulmonary embolism.
# Recurrent venous thromboembolism.
 
'''Indefinite treatment''' refers to continued anticoagulation without a pre-scheduled stop date.
 
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]].
Anticoaulation may be stopped because of:
# Risk of bleeding.
# Change in patients preference.
 
===Specific circumstances===
In patients with an underlying '''malignancy''', [[low molecular weight heparin]] is favored over warfarin based on the results of the CLOT trial.<ref>{{cite journal | author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M|title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med| year=2003 | pages=146-53 | volume=349 | issue=2  | id=PMID 12853587}}</ref>
 
Similarly, '''pregnant women''' are often maintained on low molecular weight heparin to avoid the known [[teratogenic]] effects of warfarin.
* [[Subcutaneous]] or [[Intravenous]] [[LMWH|Low molecular weight heparin]].
**Hemodynamically stable patients.
* [[Thrombolysis]]
**High Risk Hemodynamically stable patients.
**Hemodynamically Unstable patients.
*[[Pulmonary thrombectomy|Percutaneous mechanical thrombectomy]].
**High risk patients with absolute [[Thrombolysis#Contradictions|contraindications]] to Thrombolytics.
**Patients with failed Thrombolysis.
*[[LMWH|Low molecular weight heparin]] is preferred over [[Vitamin K antagonist]].
**[[Cancer]] patients.
**[[Pregnancy|Pregnant]] patients.
 
===Newer anticoagulants===
These are a class of anticoagulant drugs which act directly upon Factor X in the coagulation cascade, without using antithrombin as a mediator.'''Advantages''' of orally administered direct Xa inhibitors lie in the fact that they have a predictable effect, do not require frequent monitoring or re-dosing, are given through the mouth and not by injection and have few (known) drug interactions. '''Disadvantages''' include the currently limited prospective experience and the theoretical interactions with statin medication, as they are metabolized at least in part by the same cytochrome enzyme, CYP3A4.
 
 
==Treatment algorithm==
 
{{familytree/start |summary=PE treatment Algorithm.}}
{{familytree | | | | | | | | GMa | GMa='''Stabilize the patient'''}}
{{familytree | | | | | | | | |!| }}
{{familytree | | | | | | | | GPa | GPa='''Is [[anticoagulation]] contraindicated ?'''}}  
{{familytree | | | | |,|-|-|-|^|-|-|-|-|.| | | }}
{{familytree | | |JOE| | | | | | | |SIS| | | JOE='''Yes'''|ME=Inconclusive study|SIS='''No'''}}
{{familytree | | | |!| | | | | | | | | |!| }}
{{familytree | | |MOM| | | | | | | | SIS | | |MOM=[[Pulmonary embolism#Diagnosis|'''Diagnostic evaluation''']]|SIS=Anticoagulate with SC [[LMWH]] or IV [[Heparin|UFH]]}}
{{familytree | |,|-|^|.| | | | | | | | |!| }}
{{familytree |GPa| |JOE| | | | | |A01|GPa=PE excluded|JOE='''PE confirmed'''|A01=[[Pulmonary embolism#Diagnosis|'''Diagnostic evaluation''']]}}
{{familytree | |!| | | |!| | | | | |,|-|^|.| }}
{{familytree |C01| |C02| | |C03| |C04|C01=No further Treatment|C02='''[[Inferior vena cava filter#Pulmonary embolism inferior vena cava filter|Inferior vena cava filter]]'''|C03=PE excluded|C04='''PE confirmed'''}}
{{familytree | | | | | | | | | | |!| | | |!|}}
{{familytree | | | | | | | | | |SIS| |B02|SIS=Discontinue Anticoagulants|B02='''Clinicaly severe enough to need [[Thrombolysis]]'''}}
{{familytree | | | | | | | | | | | | |,|-|^|-|.| }}
{{familytree | | | | | | | | | | | |JOE| |SIS|JOE='''Yes'''|ME=Inconclusive study|SIS=No}}
{{familytree | | | | | | | | | | | | |!| | | |!| }}
{{familytree | | | | | | | | | | | |SIS| |B02|SIS='''Is [[thrombolytic]] Contraindicated?'''|B02=Continue Anticoagulants}}
{{familytree | | | | | | | | | | |,|-|^|-|.| }}
{{familytree | | | | | | | | |JOE| |SIS|JOE='''Yes'''|ME=Inconclusive study|SIS='''No'''}}
{{familytree | | | | | | | | | | |!| | | |!| }}
{{familytree | | | | | | | | | |SIS| |B02|SIS='''[[Pulmonary thrombectomy|Surgical emblectomy]]''' or '''[[Pulmonary embolism catheter based interventions|catheter based interventions]]'''|B02='''Hold Anticoagulation, Give Thrombolytics then resume Anticoagulations'''}}
{{familytree | | | | | | | | | | | | | | |!| | | |}}
{{familytree | | | | | | | | | | | | | |SIS|SIS=Patient shows clinical improvement}}
{{familytree | | | | | | | | | | | | |,|-|^|-|.| }}
{{familytree | | | | | | | | | | | |JOE| |SIS|JOE='''No'''|ME=Inconclusive study|SIS='''Yes'''}}
{{familytree | | | | | | | | | | | | |!| | | |!| }}
{{familytree | | | | | | | | | | | |SIS| |B02|SIS='''[[Pulmonary thrombectomy|Surgical emblectomy]]''' or '''[[Pulmonary embolism catheter based interventions|catheter based interventions]]'''|B02=Continue anticoagulation}}
{{familytree/end}}
{{familytree/end}}


==Compression Stockings==


''Note that [[edoxaban]]<ref name="pmid23991658">{{cite journal| author=Hokusai-VTE Investigators. Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S et al.| title=Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. | journal=N Engl J Med | year= 2013 | volume= 369 | issue= 15 | pages= 1406-15 | pmid=23991658 | doi=10.1056/NEJMoa1306638 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23991658  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445714 Review in: Ann Intern Med. 2014 Jan 21;160(2):JC4]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24638182 Review in: Ann Intern Med. 2014 Mar 18;160(6):JC4] </ref> has been evaluated for the treatment of [[VTE]] and is currently seeking approval for this indication.''


==References==
{{Reflist|2}}
{{WH}}
{{WS}}


==Treatment Protocol<ref name="pmid20592294">{{cite journal| author=Agnelli G, Becattini C| title=Acute pulmonary embolism. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 3 | pages= 266-74 | pmid=20592294 | doi=10.1056/NEJMra0907731 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20592294  }} </ref>==
{{familytree/start |summary=PE Pathophysiology.}}
{{familytree | | | | | | | | A01| A01='''Stabilize the patient'''
*Respiratory Support
*Hemodynamic Support
*Anticoagulation}}
{{familytree | | | | | | | |!|}}
{{familytree | | | | | | | | GMa|GMa='''Initial Treatment options (≤5 Days)'''
*[[unfractionated heparin|Unfractionated heparin]]
*[[Low molecular weight heparin|Low molecular weight heparin]]
*Factor Xa Inhibitors ([[fondaparinux]])
*[[Thrombolysis]]
*[[Pulmonary thrombectomy|Percutaneous mechanical embolectomy]]
*Surgery
*[[Vitamin K antagonist|Vitamin K antagonists]]}}
{{familytree | | | | | | | |!|}}
{{familytree | | | | | | | | A01| A01='''Long term treatment (≥3 Month)'''
*[[Vitamin K antagonist|Vitamin K antagonists]]
(INR target, 2.0-3.0)}}
{{familytree | | | | | | | |!|}}
{{familytree | | | | | | | | SON| SON='''Extended treatment (Indefinite)'''
*[[Vitamin K antagonist|Vitamin K antagonists]]
(INR target, 2.0-3.0 OR 1.5-1.9)}}
{{familytree/end}}
''
==References==
{{reflist|2}}
[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Intensive care medicine]]
{{WH}}
{{WS}}

Latest revision as of 23:53, 29 July 2020

To go back to the wikidoc page on VTE, click click here



Resident
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Pulmonary Embolism Microchapters

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Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D. [1], The APEX Trial Investigators; Associate Editor(s)-In-Chief: Kashish Goel, M.D.; Rim Halaby, M.D. [2]

This page provides algorithms about the treatment choices. For more details about the medical therapy, click here. For more details about embolectomy, click here.

Overview

Prompt recognition, diagnosis and treatment of pulmonary embolism is critical. Anticoagulant therapy is the mainstay of treatment for patients who are hemodynamically stable. If hemodynamic compromise is present, then fibrinolytic therapy is recommended.

Step 1: Confirm PE

Shown below is an algorithm depicting the initial diagnostic approach to pulmonary embolism.[1][2]

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient who is suspected to have PE have hypotension or shock?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suspected high-risk PE
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suspected non-high risk PE
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer anticoagulation
(in case there are no contraindications)
during the diagnostic workup
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is a CT available immediately?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the pretest probability of PE?
Assess the pretest probability of PE
by using one of the risk score:
- Wells score
- Geneva score
- PERC
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order echocardiography
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have RV overload?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low pretest probability
 
Intermediate pretest probability
 
High pretest probability
OR
PE is likely
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer anticoagulation
(in case there are no contraindications)
during the diagnostic workup
 
Administer anticoagulation
(in case there are no contraindications)
during the diagnostic workup
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
Yes
 
 
 
 
 
Order CT
 
 
 
 
 
Order D-dimer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive
 
Negative
 
Positive
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the patient unstable
OR
no other tests are available?
 
Is the patient stabilized
AND
CT is now available?
 
 
 
 
 
 
 
 
 
 
 
Order CT
 
PE is excluded
 
Order CT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive
 
Negative
 
Positive
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PE is excluded
 
Consider thrombolytic therapy or embolectomy
 
Order CT
 
PE is confirmed
 
PE is excluded
 
PE is confirmed
 
PE is excluded
 
PE is confirmed
 
PE is excluded
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive for PE
 
Negative for PE
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PE is confirmed
 
PE is excluded
 
 

Step 2: Initial Treatment

Shown below is an algorithm depicting the initial management of pulmonary embolism.[1][2]

 
 
 
 
 
 
 
 
 
 
Assess the severity of pulmonary embolism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Massive PE
(also known as high-risk PE)
Cardiogenic shock
OR
Persistent hypotension (≤90mmHg)
OR
Drop of the blood pressure by ≥ 40mmHg for > 15 min[3]
OR
Pulselessness
OR
Profound bradycardia (<40 bpm) with findings of shock[4]
 
 
 
 
 
Submassive PE
(also know as intermediate-risk PE)
Right ventricular dysfunction
AND/OR
Myocardial injury (Troponin +)
 
 
 
 
 
Low-risk PE
No cardiogenic shock
AND
No hypotension
AND
No right ventricular dysfunction
AND
No myocardial injury (Troponin -)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Provide hemodynamic and respiratory support

Begin high dose unfractionated heparin [3]: Bolus 10.000 U

Continuous infusion of at least 1250 U/hour for a targeted apTT of at least 80 s

Administer rapidly 500-1000 mL of normal saline (Caution with fluid overload)[3]
Have a low threshold for ionotropes (dopamine or dobutamine)[3]

Administer oxygen for hypoxemic patients[3]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is there any contraindication for fibrinolytic therapy?
 
 
 
 
 
Is there any contraindication for anticoagulation therapy?
 
 
 
 
 
Is there any contraindication for anticoagulation therapy?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO
 
YES
 
NO
 
YES
 
NO
 
YES
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discontinue unfractionated heparin
AND
Begin fibrinolytic therapy
 
Surgical pulmonary embolectomy
OR
Percutaneous catheter embolectomy
 
Anticoagulation therapy
AND
Hospital admission
 
IVC filter
AND
Hospital admission
 
Anticoagulation therapy
AND
Early discharge/home treatment
 
IVC filter
AND
Early discharge/home treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient fail to improve
OR
Develop cardiogenic shock?
OR
Develop hypotension?
 
 
 
 
 
 
 
Does the patient fail to improve
OR
Develop cardiogenic shock?
OR
Develop hypotension (<90 mmHg)?
OR
Develop respiratory distress (SaO2<95% with Borg score>8 or altered mental status)
OR
Have moderate to severe RV dysfunction (RV hypokinesis or estimated RVSP>40 mmHg)
OR
Elevated biomarkers (troponin> upper limit of normal, BNP>100 pg/mL, or pro-BNP>900 pg/mL)[4]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
NO
 
YES
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical pulmonary embolectomy
OR
Percutaneous catheter embolectomy
 
Continue with the same treatment
 
Is there any contraindication for fibrinolytic therapy?
 
Continue with the same treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO
 
YES
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hold anticoagulation and give thrombolytics
 
Surgical pulmonary embolectomy
OR
Percutaneous catheter embolectomy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient fail to improve?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical pulmonary embolectomy
OR
Percutaneous catheter embolectomy
 
Continue with the same treatment

Initial Anticoagulation Therapy

 
 
 
Begin initial anticoagulation therapy in:
Confirmed PE
OR
High or intermediate probability of PE while awaiting the diagnostic tests
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the patient high risk or non-high risk?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High risk
 
 
 
Non-high risk
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Administer IV unfractionated heparin[5]
 
 
 
Does the patient have:
High risk of bleeding
OR
Severe renal failure?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Administer unfractionated heparin:[1]
❑ IV injection
OR
❑ SC injection
 
❑ Administer ONE of the following:[5]
❑ SC low molecular weight heparin (1st line)
❑ SC fondaparinux (1st line)
❑ IV unfractionated heparin
❑ SC unfractionated heparin

Step 3: Long Term Anticoagulation Therapy

The long term management of PE depends on whether the episode is the first one or not, whether it is provoked or unprovoked, and on the risk of bleeding of the patient. Among non cancer patients, the first line therapy for long term management of PE is vitamin K antagonists (VKA); whereas the first line treatment among cancer patients is low molecular weight heparin. If long term treatment with VKA is decided, VKA should be started at the same day with heparin allowing for at least 5 days of overlap until the INR is ≥2 for at least 24 hours. Among patients on extended anticoagulation therapy, the risk vs benefits of the anticoagulation therapy should be assessed regularly (for example annually).[2]

 
 
 
 
 
 
 
 
 
Is this the first episode of PE?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
 
 
 
 
 
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is PE provoked?
 
 
 
 
 
 
 
What is the risk of bleeding?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes, transient reversible risk factor
 
Yes, cancer
 
No (unprovoked)
 
Low or moderate
 
High
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Therapy for 3 months
VKA (first line)
OR
LMWH
OR
Dabigatran
OR
Rivaroxaban
 
Extended therapy or until cancer is cured
LMWH (first line)
OR
VKA
OR
Dabigatran
OR
Rivaroxaban
 
Therapy for ≥ 3 months
VKA (first line)
OR
LMWH
OR
Dabigatran
OR
Rivaroxaban
 
Extended therapy
VKA (first line)
OR
LMWH
OR
Dabigatran
OR
Rivaroxaban
 
Therapy for 3 months
VKA (first line)
OR
LMWH
OR
Dabigatran
OR
Rivaroxaban
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Re-assess the risk of bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low or moderate
 
High
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Extended therapy
 
Do not extend the therapy beyond the initial 3 months
 
 
 
 
 
 


Note that edoxaban[6] has been evaluated for the treatment of VTE and is currently seeking approval for this indication.

References

  1. 1.0 1.1 1.2 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P; et al. (2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)". Eur Heart J. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870.
  2. 2.0 2.1 2.2 Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ; et al. (2012). "Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e419S–94S. doi:10.1378/chest.11-2301. PMC 3278049. PMID 22315268.
  3. 3.0 3.1 3.2 3.3 3.4 Kucher N, Goldhaber SZ (2005). "Management of massive pulmonary embolism". Circulation. 112 (2): e28–32. doi:10.1161/CIRCULATIONAHA.105.551374. PMID 16009801.
  4. 4.0 4.1 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ; et al. (2011). "Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association". Circulation. 123 (16): 1788–830. doi:10.1161/CIR.0b013e318214914f. PMID 21422387.
  5. 5.0 5.1 Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ; et al. (2012). "Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e152S–84S. doi:10.1378/chest.11-2295. PMC 3278055. PMID 22315259.
  6. Hokusai-VTE Investigators. Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S; et al. (2013). "Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism". N Engl J Med. 369 (15): 1406–15. doi:10.1056/NEJMoa1306638. PMID 23991658. Review in: Ann Intern Med. 2014 Jan 21;160(2):JC4 Review in: Ann Intern Med. 2014 Mar 18;160(6):JC4

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