Pulmonary embolism medical therapy: Difference between revisions

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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''']]
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{{Pulmonary embolism}}
{{Pulmonary embolism}}
{{PE editors}}
'''Editor(s)-In-Chief:''' {{ATI}}, [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com]; {{AE}} {{CZ}}; {{Rim}}
 
'''For the algorithms about the treatment choices, click [[pulmonary embolism treatment algorithm|here]].'''


==Overview==
==Overview==
In most cases, anticoagulant therapy is the mainstay of treatment.  
Medical therapy for pulmonary embolism (PE) includes [[anticoagulation therapy]] and [[fibrinolytic therapy]].  Parenteral [[anticoagulation therapy]] with either [[unfractionated heparin]], [[low molecular weight heparin]] ([[LMWH]]), or [[fondaparinux]] is indicated in the initial treatment of patients with PE who do not have any contraindications for anticoagulation.  Initial parenteral anticoagulation therapy should be started before the completion of the diagnostic workup among patients who have a high pretest probability of PE as well as among those with intermediate pretest probability of PE and an expected delay in the diagnostic results of more than 4 hours.<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: 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=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>  [[Thrombolytic therapy]] is indicated for the treatment of [[Pulmonary embolism classification#Massive Pulmonary Embolism|massive PE]], also known as [[Pulmonary embolism classification#Massive Pulmonary Embolism|high-risk PE]].<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>  Patients with PE require long term anticoagulation therapy with agents such as [[vitamin K antagonist]]s, [[LMWH]], [[dabigatran]], or [[rivaroxaban]].
 
The need for treatment of subsegmental pulmonary emboli is uncertain.<ref name="pmid24771493">{{cite journal| author=Yoo HH, Queluz TH, El Dib R| title=Anticoagulant treatment for subsegmental pulmonary embolism. | journal=Cochrane Database Syst Rev | year= 2014 | volume= 4 | issue=  | pages= CD010222 | pmid=24771493 | doi=10.1002/14651858.CD010222.pub2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24771493  }} </ref>
 
==Anticoagulation Therapy==
* The most common cause of mortality in patients with a PE, is a recurrent PE occurring within a 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 an acute PE.  Anticoagulation prevents further clot formation and extension, therefore it should be started as early as possible.  Anticoagulation does not disaggregate existing clot, but it does facilitate the action of the body's endogenous lytic system.<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>
* Certain conditions like [[pericardial tamponade]] and [[aortic dissection]] can mimic pulmonary embolism. The use of anticoagulants is contraindicated in these medical conditions. Proceed with caution if these conditions are high on the differential.
* Anticoagulation therapy can be either parenteral or oral.
 
==Parenteral Anticoagulation Therapy==
===Heparin ===
* Heparin binds to the enzyme inhibitor antithrombin III (AT).  The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably [[factor Xa]].
 
* The side effects of heparin include [[bleeding]], [[heparin-induced thrombocytopenia]] and [[osteoporosis]].<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: 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=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>  In patients with suspected or confirmed [[heparin-induced thrombocytopenia]], [[lepirudin]] or [[argatroban]] should be used.
 
* The anticoagulant effects of [[heparin]] can be reversed with IV [[protamine sulfate]].<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: 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=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
 
====Heparin Dosage====
Shown below is a table depicting the dosage of heparin for the treatment of [[pulmonary embolism]].  Note that the dose of heparin used in the treatment of [[acute coronary syndrome]] is lower than that used for the treatment of PE.<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: 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=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 30%" align=center | '''Mode of administration of Heparin'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 70%" align=center | '''Dosage'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |'''''IV injection'''''
|style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |80 U/kg as bolus, followed by 18 U/kg/h, OR <br><br>
70 U/kg as bolus, followed by 15 U/kg/h for stroke or cardiac patients<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>
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |'''''SC injection'''''
|style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |333 U/kg as bolus, followed by 250 U/kg<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 anticoag
ulant 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>
|}
 
====Adjustment of Heparin Dosage According to aPTT====
aPTT should be monitored during treatment with Heparin.  Prolongation of apTT correlates with an elevated serum concentration  of [[heparin]] and requires adjustment of the dosage.  Shown below is a table depicting the variation in the dosage according the aPTT.
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 30%" align=center | '''aPTT'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 70%" align=center | '''Variation in the dosage'''<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>
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''< 1.2 x control (<35 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | Bolus: 80 U/kg <br> Infusion rate: increase by 4 U/kg/h
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''1.2-1.5 x control (35-45 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |Bolus: 40 U/kg <br> Infusion rate: increase by 2 U/kg/h
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''1.5-2.3 x control (46-70 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | Continue the same dosage
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''2.3-3.0 x control (71-90 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | Infusion rate: decrease by 2 U/kg/h
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''> 3.0 x control (>90s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | Stop infusion for a period of 1 hour, then<br>Infusion rate: decrease by 3 U/kg/h
|-
|}
 
====Platelet Monitoring====
Among patients started on [[heparin]], if the risk of [[heparin induced thrombocytopenia]] is more than 1%, monitor [[platelet count]] every 2 to 3 days from the 4th until the 14th day of treatment or until the discontinuation of [[heparin]].<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>
 
=== Low Molecular Weight Heparin ===
* [[LMWH]] is used as a first line therapy for the initial anticoagulation therapy for PE among patients with non-high risk PE.<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: 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=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
 
* In addition, [[LMWH]] can also be used for the long term anticoagulation treatment for PE, but [[vitamin K antagonist]] are recommended as first line therapy.  However, among cancer patients with provoked PE, [[LMWH]] is the first line therapy for the long term anticoagulation treatment.<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: 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=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>  [[LMWH]] is preferred in pregnancy to avoid the known [[teratogenic]] effects of [[warfarin]].
 
* [[LMWH]] is administered subcutaneously and does not require routine coagulation monitoring.
 
* The recommended doses for treatment of PE are:<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: 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=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily) OR 1.5 mg/kg once daily
** [[Tinzaparin]] : 175 U/Kg body weight (once daily)
 
=== Fondaparinux===
* [[Fondaparinux]] is used as a first line therapy for the initial anticoagulation therapy for PE among patients with non-high risk PE.  The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of factor Xa.  Fondaparinux does not require routine coagulation monitoring.
 
* Recommended doses for the treatment of [[PE]] depend on the weight of the patient:
** Weight <50 Kg: 5 mg (once daily)
** Weight between 50 Kg to 100 Kg: 7.5 mg (once daily)
** Weight >100 Kg: 10 mg (once daily)
 
==Oral Anticoagulation Therapy==
 
=== Vitamin K Antagonist===
* [[Vitamin K antagonist]] is the first line therapy for long term anticoagulation treatment of [[pulmonary embolism]], with the exception of patients with cancer among whom [[LMWH]] is preferred over [[warfarin]].<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>
 
* [[Warfarin]] should not be administered in pregnancy and [[LMWH]] should be use instead.
 
* Warfarin should be started as soon as possible following the initiation of parenteral anticoagulation therapy, preferably at the same day.  Parenteral anticoagulation therapy should be continued for at least 5 days concomitantly with [[warfarin]] until INR reaches 2.<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>
 
* [[Warfarin]] is administered as follows:
** Begin with 5 mg [[warfarin]] for 2 days followed by dosing based on the [[INR]].
** Target [[INR]] is 2-3.
** Monitor [[INR]] monthly.
** If the [[INR]] is stable but there is one value 0.5 below or above the target range, continue the same dose and repeat [[INR]] within 1-2 weeks.
* [[NSAID]]s, [[COX2]] selective NSAIDs and some antibiotics should be avoided when [[warfarin]] is administered.<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>
 
===Factor X Inhibitors===
[[Rivaroxaban]] is an oral [[factor X inhibitor]]s that can be used in the long term treatment of PE.
 
=== Direct Thrombin Inhibitors===
[[Dabigatran]] is an oral [[direct thrombin inhibitor]]s that can be used in the long term treatment of PE.
 
== Thrombolysis ==
Thrombolysis, also known as clot busting, is the breakdown of [[thrombosis|blood clots]] by [[pharmacology|pharmacological]] agents. Thrombolytic agents activate the enzyme [[plasminogen]] into [[plasmin]] which is responsible for the breakdown of [[fibrin]].  The thrombolytic agents that are FDA approved are: [[streptokinase]], [[urokinase]], and [[alteplase]].<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>
 
===Indications===
* Thrombolytic therapy is indicated for the treatment of massive PE, also known as high-risk PE.<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>
 
* Thrombolytic therapy is currently not indicated for the treatment of submassive PE, also known as intermediate-risk PE.  Patients with intermediate-risk PE have evidence of [[right ventricular dysfunction]] or [[myocardial necrosis]] in the absence of [[hypotension]].  According to the The Pulmonary Embolism Thrombolysis (PEITHO) trial, fibrinolytic therapy in intermediate-risk PE decreased the rate of the compensation of the hemodynamic status at an expense of an elevated rate of major [[hemorrhage]] and [[stroke]].<ref name="pmid24716681">{{cite journal| author=Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J et al.| title=Fibrinolysis for patients with intermediate-risk pulmonary embolism. | journal=N Engl J Med | year= 2014 | volume= 370 | issue= 15 | pages= 1402-11 | pmid=24716681 | doi=10.1056/NEJMoa1302097 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24716681  }} </ref>  A recent metaanalysis of 16 randomized clinical trials of 2115 PE patients, 70.87% of whom are intermediate-risk patients, revealed that thrombolytic therapy in PE is associated with a decreased rate of mortality and an increase rate of major [[bleed]] and [[intracranial hemorrhage]], particularly among patients who are older than 65 years.<ref name="pmid24938564">{{cite journal| author=Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P et al.| title=Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. | journal=JAMA | year= 2014 | volume= 311 | issue= 23 | pages= 2414-21 | pmid=24938564 | doi=10.1001/jama.2014.5990 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24938564  }} </ref>
 
* When patients initially classified as intermediate-risk fail to improve, or develop [[cardiogenic shock]], [[hypotension]] (<90 mmHg), or [[respiratory distress]] (SaO2<95% with Borg score>8 or altered mental status), they should be administered fibrinolytic therapy.<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>
 
=== Dosage ===
Shown below is the dosage schedule for the thrombolytic agents:<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>
*[[Streptokinase]] (FDA-approved)
**'''Loading dose:''' 250 000 IU over 30 min
**'''Maintenance dose:''' 100 000 IU/h over 12–24 hr
**'''Accelerated regimen:''' 1.5 million IU over 2 hr
*[[Urokinase]] (FDA-approved)
**'''Loading dose:''' 4400 IU/kg over 10 min
**'''Maintenance dose:''' 4400 IU/kg/h over 12–24 hr
**'''Accelerated regimen:''' 3 million IU over 2 hr
*[[Recombinant tissue plasminogen activator|Recombinant tissue plasminogen activator (rtPA)]]<ref name="pmid19041539">{{cite journal| author=Fengler BT, Brady WJ| title=Fibrinolytic therapy in pulmonary embolism: an evidence-based treatment algorithm. | journal=Am J Emerg Med | year= 2009 | volume= 27 | issue= 1 | pages= 84-95 |pmid=19041539 | doi=10.1016/j.ajem.2007.10.021 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19041539  }} </ref>
** [[Alteplase]] (FDA-approved): 10-mg IV bolus followed by 90 mg IV infusion over 2 hours
** [[Reteplase]]: 10-U IV bolus followed in 30 mins by another 10-U IV bolus
** [[Tenecteplase]]: 0.5-mg/kg IV bolus (max 50mg)
 
===Administration===
* When indicated, [[fibrinolytic therapy]] should be administered for a short infusion time (for 2 hours) rather than over prolonged perfusion (for 24 hours).<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>
 
* In addition, [[fibrinolytic therapy]] should be administered via a [[peripheral vein]] rather than [[pulmonary artery]] catheter.<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>
 
* Anticoagulation therapy should be withheld during the 2 hours of fibrinolytic infusion.
 
====Systemic Fibrinolysis vs Ultrasound Assisted Catheter Directed Thrombolysis====
Fibrinolysis in PE can be achieved either by the systemic administration of fibrinolytic agents or by ultrasound-assisted catheter-directed thrombolysis.  Catheter-directed thrombolysis has been reported to improve the right ventricular function among patients with submassive PE.<ref name="pmid24497337">{{cite journal| author=Engelberger RP, Kucher N| title=Ultrasound-assisted thrombolysis for acute pulmonary embolism: a systematic review. | journal=Eur Heart J | year= 2014 | volume= 35 | issue= 12 | pages= 758-64 | pmid=24497337 | doi=10.1093/eurheartj/ehu029 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24497337  }} </ref>  In fact, The Ultrasound Accelerated Thrombolysis of Pulmonary Embolism (ULTIMA) trial, a randomized controlled trial of 59 patients with intermediate risk PE, demonstrated that catheter-directed thrombolysis with a low dose <20mg [[rt-PA]] was superior to anticoagulation ([[heparin]] alone) in improving the [[RV|right ventricular]] function without an increase in [[bleeding]].<ref name="pmid24226805">{{cite journal| author=Kucher N, Boekstegers P, Müller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T et al.| title=Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. | journal=Circulation | year= 2014 | volume= 129 | issue= 4 | pages= 479-86 | pmid=24226805 | doi=10.1161/CIRCULATIONAHA.113.005544 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24226805  }} </ref>  The advantage of catheter-directed thrombolysis compared to systemic thrombolysis is a less [[bleeding]] rate; however, catheter-directed thrombolysis requires extensive resources and expertise.  Large scale clinical trials are needed to compare catheter-directed thrombolysis vs systemic fibrinolysis as well as catheter-directed thrombolysis vs [[anticoagulation therapy]].
 
=== Contraindications ===
Shown below is a table summarizing the absolute and relative contraindications to [[fibrinolytic therapy]] among [[pulmonary embolism]] patients.<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>
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=center | '''Absolute contraindications'''||style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=center | '''Relative contraindications'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |❑ Previous [[hemorrhagic stroke]] or [[stroke]] of unknown origin <br>
❑ [[Ischemic stroke]] within the last 6 months<br>
❑ [[Central nervous system]] tumor or damage <br>
❑ Major [[trauma]], head injury, or [[surgery]] within the last 3 weeks <br>
❑ [[Gastrointestinal bleed]] within the last month <br>
❑ Known [[bleeding]] <br>
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |❑ [[Transient ischemic attack]] within the last 6 months <br>
❑ [[Anticoagulation|Oral anticoagulant therapy]] intake <br>
❑ Advanced [[liver disease]] <br>
❑ [[Infective endocarditis]] <br>
❑ [[Peptic ulcer disease]] that is currently active <br>
❑ [[Pregnancy]] or within 1 week post partum <br>
❑ Punctures that are non-compressible <br>
❑ [[Resuscitation|Traumatic resuscitation]] <br>
❑ [[Systolic blood pressure]] >180 mmHg refractory to treatment
|}
 
=== Complications of Thrombolytic Therapy===
* [[Major hemorrhage]] - 10%
* Non major [[hemorrhage]] - 20%
* [[Intracranial hemorrhage]] - 0.5%<ref name="urlThrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism">{{cite web |url=http://circ.ahajournals.org/content/110/6/744.abstract?sid=382ce1b3-7625-4ac5-9c41-d8da4ac70d41 |title=Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism |format= |work= |accessdate=2012-10-06}}</ref>
 
===Contraindicated medications===
{{MedCondContrAbs
 
|MedCond = Pulmonary embolism|Alteplase|Conjugated estrogens/bazedoxifene|Esterified estrogens|Medroxyprogesterone|Norelgestromin and Ethinyl Estradiol | Progesterone|Raloxifene}}
 
==2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis (DO NOT EDIT)<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>==
===Recommendations for Initial Treatment of Acute PE ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In patients with acute [[PE]], we recommend initial treatment with parenteral anticoagulation (LMWH, fondaparinux, IV UFH, or SC UFH) over no such initial treatment. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' In patients with acute [[PE]], we recommend early initiation of [[VKA]] (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the INR is 2.0 or above for at least 24 h. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In patients with acute [[PE]] who are treated with anticoagulants, we recommend against the use of an [[IVC filter]]. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' In patients with acute [[PE]] and contraindication to anticoagulation, we recommend the use of an [[IVC filter]]. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' In most patients with acute [[PE]] not associated with hypotension, we recommend against systemically administered thrombolytic therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class II]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with low-risk [[PE]] and whose home circumstances are adequate, we suggest early discharge over standard discharge (eg,after the first 5 days of treatment). ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients with acute [[PE]] and an [[IVC filter]] inserted as an alternative to anticoagulation, we suggest a conventional course of anticoagulant therapy if their risk of bleeding resolves. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with a high clinical suspicion of acute [[PE]], we suggest treatment with parenteral anticoagulants compared with no treatment while awaiting the results of diagnostic tests. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''4.''' In patients with an intermediate clinical suspicion of acute [[PE]], we suggest treatment with parenteral anticoagulants compared with no treatment if the results of diagnostic tests are expected to be delayed for more than 4 h. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''5.''' In patients with a low clinical suspicion of acute [[PE]], we suggest not treating with parenteral anticoagulants while awaiting the results of diagnostic tests provided that test results are expected within 24 h. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''6.''' In patients with acute [[PE]], we suggest [[LMWH]] or [[fondaparinux]] over IV UFH ([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]] for LMWH)''; ''[[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]]'' for fondaparinux) , and over SC UFH (''[[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]]'' for LMWH; ''[[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]]'' for fondaparinux).<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''7.''' In patients with acute [[PE]] treated with [[LMWH]], we suggest once- over twice-daily administration. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''8.''' In patients with acute [[PE]] associated with hypotension (eg, systolic BP , 90 mm Hg) who do not have a high risk of bleeding, we suggest systemically administered thrombolytic therapy over no such therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''9.''' In selected patients with acute [[PE]] not associated with hypotension and with a low risk of bleeding whose initial clinical presentation or clinical course after starting anticoagulant therapy suggests a high risk of developing hypotension, we suggest administration of thrombolytic therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''10.''' In patients with acute [[PE]], when a thrombolytic agent is used, we suggest short infusion times (eg, a 2-h infusion) over prolonged infusion times (eg, a 24-h infusion). ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''11.''' In patients with acute [[PE]], when a thrombolytic agent is used, we suggest administration through a peripheral vein over a pulmonary artery catheter. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''12.''' In patients with acute [[PE]] associated with hypotension and who have (i) contraindications to thrombolysis, (ii) failed thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter-assisted thrombus removal over no such intervention. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''13.''' In patients with acute [[PE]] associated with hypotension, we suggest surgical pulmonary embolectomy over no such intervention if they have (i) contraindications to thrombolysis, (ii) failed thrombolysis or catheter-assisted embolectomy, or (iii) shock that is likely to cause death before thrombolysis can take effect (e.g., within hours), provided surgical expertise and resources are available. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
 
=== 2012 ACCP Guidelines - Recommendations for Long-term Treatment of PE (DO NOT EDIT)<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>===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[American College of Chest Physicians#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In patients with [[PE]] provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period, (ii) treatment of a longer time limited period (eg, 6 or 12 months), or (iii) extended therapy (regardless of bleeding risk). ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' In patients with [[PE]] provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period, (ii) treatment of a longer time-limited period (eg, 6 or 12 months), and (iii) extended therapy if there is a high bleeding risk''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''. We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Class II, Level of Evidence B).<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In patients with an unprovoked [[PE]], we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration. After 3 months of treatment, patients with unprovoked [[PE]] should be evaluated for the risk-benefit ratio of extended therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' In patients with a second unprovoked [[VTE]], we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])'', and we suggest extended anticoagulant therapy in those with a moderate bleeding risk (Class II, Level of Evidence B).<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' In patients with a first [[VTE]] that is an unprovoked [[PE]] and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''6.''' In patients with [[PE]] who are treated with [[VKA]], we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) over a lower (INR < 2.0) or higher (INR 3.0-5.0) range for all treatment durations. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''7.''' In patients with [[PE]] and active cancer, if there is a low or moderate bleeding risk, we recommend extended anticoagulant therapy over 3 months of therapy ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])'', and if there is a high bleeding risk, we suggest extended anticoagulant therapy (Class II, Level of Evidence B).<nowiki>"</nowiki>
|}


===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>===
{|class="wikitable"
{{familytree/start |summary=PE Pathophysiology.}}
|-
{{familytree | | | | | | | | A01| A01='''Stabilize the patient'''
| colspan="1" style="text-align:center; background:LemonChiffon"| [[American College of Chest Physicians#Classes of Recommendations|Class II]]
*Respiratory Support
|-
*Hemodynamic Support
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with a first [[VTE]] that is an unprovoked [[PE]] and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
*Anticoagulation}}
|-
{{familytree | | | | | | | |!|}}
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients with a second unprovoked [[VTE]] who have a high bleeding risk, we suggest 3 months of therapy over extended therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
{{familytree | | | | | | | | GMa|GMa='''Initial Treatment options (≤5 Days)'''  
|-
*[[unfractionated heparin|Unfractionated heparin]]
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with [[PE]] and no cancer, we suggest [[VKA]] therapy over [[LMWH]] for long-term therapy. For patients with PE and no cancer who are not treated with [[VKA]] therapy, we suggest [[LMWH]] over [[dabigatran]] or [[rivaroxaban]] for long-term therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
*[[Low molecular weight heparin|Low molecular weight heparin]]
|-
*Factor Xa Inhibitors ([[fondaparinux]])
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''4.''' In patients with [[PE]] and cancer, we suggest [[LMWH]] over [[VKA]] therapy ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''. In patients with [[PE]] and cancer who are not treated with [[LMWH]], we suggest [[VKA]] over [[dabigatran]] or [[rivaroxaban]] for long-term therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
*[[Thrombolysis]]
|-
*[[Pulmonary thrombectomy|Percutaneous mechanical embolectomy]]
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''5.''' In patients with [[PE]] who receive extended therapy, we suggest treatment with the same anticoagulant chosen for the first 3 months. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
*Surgery
|-
*[[Vitamin K antagonist|Vitamin K antagonists]]}}
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''6.''' In patients who are incidentally found to have asymptomatic [[PE]], we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic [[PE]]. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
{{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}}


''
=== 2012  ACCP Guidelines - Recommendations for Anticoagulation in Chronic Thromboembolic Pulmonary Hypertenion (DO NOT EDIT)<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>===


==Anticoagulation==


* [[Subcutaneous]] or [[Intravenous]] [[LMWH|Low molecular weight heparin]].
{|class="wikitable"
**Hemodynamically stable patients.
|-
* [[Thrombolysis]]
| colspan="1" style="text-align:center; background:LightGreen"|[[American College of Chest Physicians#Classes of Recommendations|Class I]]
**High Risk Hemodynamically stable patients.
|-
**Hemodynamically Unstable patients.
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In patients with chronic thromboembolic [[pulmonary hypertension]], we recommend extended anticoagulation over stopping therapy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
*[[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.


==Dosage==
{|class="wikitable"
Another validated nomogram has proposed the following dosage<ref name="pmid8694662">{{cite journal| author=Raschke RA, Gollihare B, Peirce JC| title=The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. | journal=Arch Intern Med | year= 1996 | volume= 156 | issue= 15 | pages= 1645-9 | pmid=8694662 | doi= | pmc= | url= }} </ref>.
|-
*'''[[Low molecular weight heparin]]'''
| colspan="1" style="text-align:center; background:LemonChiffon"|[[American College of Chest Physicians#Classes of Recommendations|Class II]]
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily).
|-
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In selected patients with chronic thromboembolic [[pulmonary hypertension]], such as those with central disease under the care of an experienced throm boendarterectomy team, we suggest pulmonary thromboendarterectomy over no pulmonary thromboendarterectomy. ''([[American College of Chest Physicians#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|}


*'''[[Factor Xa Inhibitor|Factor Xa Inhibitors]]'''
==2011 AHA Scientific Statement- Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension (DO NOT EDIT)<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>==
**[[Fondaparinux]] :
***Patient weighing less than 50 Kg (110 lb) : 5 mg (once daily).
***Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
***Patient weighing more than 100 Kg (220 lb) : 10 mg (once daily).


*'''[[Unfractionated heparin]] '''
===2011 ACC/AHA Guidelines- Recommendations for Initial Anticoagulation for Acute PE (DO NOT EDIT)<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>===
**Loading Dose: 80 IU/Kg or 5000 IU
**Mantainace Dose: 18 IU/Kg/Hr to achieve a target [[aPTT]] 1.5 to 2.5 times the normal value.


== ESC Guidelines treatment High-risk pulmonary embolism (DO NOT EDIT)==
{|class="wikitable"
<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>
|-
{{cquote|
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
===[[European society of cardiology#Classes of Recommendations|Class I]]===
|-
'''1.''' Anticoagulation with unfractionated heparin should be initiated without delay in patients with high-risk PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Therapeutic anticoagulation with subcutaneous LMWH, intravenous or subcutaneous UFH with monitoring, unmonitored weight-based subcutaneous UFH, or subcutaneous fondaparinux should be given to patients with objectively confirmed PE and no contraindications to anticoagulation  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Therapeutic anticoagulation during the diagnostic workup should be given to patients with intermediate or high clinical probability of PE and no contraindications to anticoagulation  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''. <nowiki>"</nowiki>


'''2.''' Systemic hypotension should be corrected to prevent progression of RV failure and death due to PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''
|}


'''3.''' Vasopressive drugs are recommended for hypotensive patients with PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''
===2011  ACC/AHA Guidelines- Recommendations for Fibrinolysis for Acute PE (DO NOT EDIT)<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>===


===[[European society of cardiology#Classes of Recommendations|Class IIa]]===
{|class="wikitable"
'''4.''' Dobutamine and dopamine may be used in patients with PE, low cardiac output and normal blood pressure. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''  All patients should be risk stratified. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.'''  For most patients (stable) thrombolytic therapy not indicated. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.'''  For unstable patients, thrombolytic therapy should be used unless major contraindications. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' Systemic therapy preferred over catheter directed lysis. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.'''  Short infusions times ( nearly 2 hours) are preferred. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])<nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightCoral"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (No Benefit)
|-
| bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Fibrinolysis is not recommended for patients with low-risk PE or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''. <nowiki>"</nowiki>
|-
| bgcolor="LightCoral"|<nowiki>"</nowiki>'''2.''' Fibrinolysis is not recommended for undifferentiated cardiac arrest''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''. <nowiki>"</nowiki>
|}


===[[European society of cardiology#Classes of Recommendations|Class III]]===
{| class="wikitable"
'''5.''' Aggressive fluid challenge is not recommended. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Fibrinolysis is reasonable for patients with massive acute PE and acceptable risk of bleeding complications. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


===[[European society of cardiology#Classes of Recommendations|Class I]]===
{| class="wikitable"
'''6.''' Oxygen should be administered in patients with hypoxaemia.''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Fibrinolysis may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory insufficiency, severe RV dysfunction, or major myocardial necrosis) and low risk of bleeding complications''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''.<nowiki>"</nowiki>
|}


'''7.''' Thrombolytic therapy should be used in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension.''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
==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)(DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>==


'''8.''' Surgical pulmonary embolectomy is a recommended therapeutic alternative in patients with high-risk PE in whom thrombolysis
===Treatment of High-Risk Pulmonary Embolism (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>===
is absolutely contraindicated or has failed.''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''


===[[European society of cardiology#Classes of Recommendations|Class IIb]]===
{| class="wikitable"
'''9.'''Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk patients when thrombolysis is absolutely contraindicated or has failed. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''
|-
}}
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Anticoagulation with unfractionated heparin should be initiated without delay in patients with high-risk PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Systemic hypotension should be corrected to prevent progression of RV failure and death due to PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' Vasopressive drugs are recommended for hypotensive patients with PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' Oxygen should be administered in patients with hypoxaemia.''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' Thrombolytic therapy should be used in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension.''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>


==ESC Guidelines treatment Non-high-risk pulmonary embolism (DO NOT EDIT)==
|-
<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''6.''' Surgical pulmonary embolectomy is a recommended therapeutic alternative in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed.''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
{{cquote|
|}
===[[European society of cardiology#Classes of Recommendations|Class I]]===
'''1.''' Anticoagulation should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic workup is still ongoing. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''


'''2.''' Use of LMWH or fondaparinux is the recommended form of initial treatment for most patients with non-high-risk PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightCoral"|[[European society of cardiology#Classes of Recommendations|Class III]]


'''3.''' In patients at high risk of bleeding and in those with severe renal dysfunction, unfractionated heparin with an aPTT target range of 1.5–2.5 times normal is a recommended form of initial treatment. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''  
|-
| bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Aggressive fluid challenge is not recommended. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


'''4.''' Initial treatment with unfractionated heparin, LMWH or fondaparinux should be continued for at least 5 days and ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' may be replaced by vitamin K antagonists only after achieving target INR levels for at least 2 consecutive days ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIa]]


===[[European society of cardiology#Classes of Recommendations|Class IIb]]===
|-
'''5.''' Routine use of thrombolysis in non–high-risk PE patients is not recommended, but it may be considered in selected patients
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Dobutamine and dopamine may be used in patients with PE, low cardiac output and normal blood pressure. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
with intermediate-risk PE ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''
|}
===[[European society of cardiology#Classes of Recommendations|Class III]]===
'''6.''' Thrombolytic therapy should be not used in patients with low-risk PE ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''
}}


==ESC Guidelines Recommendations Long-term treatment (DO NOT EDIT)==
{| class="wikitable"
<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>
|-
{{cquote|
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIb]]
===[[European society of cardiology#Classes of Recommendations|Class I]]===
'''1.''' For patients with PE secondary to a transient (reversible) risk factor, treatment with a VKA is recommended for 3 months.''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''


'''2.''' For patients with unprovoked PE, treatment with a VKA is recommended for at least 3 months. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk patients when thrombolysis is absolutely contraindicated or has failed. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}


'''3.''' For patients with a second episode of unprovoked PE, long-term treatment is recommended. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
===Treatment of Non-High-Risk Pulmonary Embolism (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>===


'''4.''' In patients who receive long-term anticoagulant treatment, the risk/benefit ratio of continuing such treatment should be reassessed at regular intervals. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Anticoagulation should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic workup is still ongoing. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Use of LMWH or fondaparinux is the recommended form of initial treatment for most patients with non-high-risk PE. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In patients at high risk of bleeding and in those with severe renal dysfunction, unfractionated heparin with an aPTT target range of 1.5–2.5 times normal is a recommended form of initial treatment. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' Initial treatment with unfractionated heparin, LMWH or fondaparinux should be continued for at least 5 days and ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' may be replaced by vitamin K antagonists only after achieving target INR levels for at least 2 consecutive days ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[European society of cardiology#Classes of Recommendations|Class III]]
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Thrombolytic therapy should be not used in patients with low-risk PE ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[European society of cardiology#Classes of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Routine use of thrombolysis in non–high-risk PE patients is not recommended, but it may be considered in selected patients with intermediate-risk PE ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


'''5.''' In patients with PE, the dose of VKA should be adjusted to maintain a target INR of 2.5 (range 2.0–3.0) regardless of treatment duration. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
===Recommendations Long-Term Treatment (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>===


===[[European society of cardiology#Classes of Recommendations|Class IIb]]===
{| class="wikitable"
'''6.''' Patients with a first episode of unprovoked PE and low risk of bleeding, and in whom stable anticoagulation can be achieved, may be considered for long-term oral anticoagulation. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' For patients with PE secondary to a transient (reversible) risk factor, treatment with a VKA is recommended for 3 months.''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' For patients with unprovoked PE, treatment with a VKA is recommended for at least 3 months. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' For patients with a second episode of unprovoked PE, long-term treatment is recommended. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' In patients who receive long-term anticoagulant treatment, the risk/benefit ratio of continuing such treatment should be reassessed at regular intervals. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' In patients with PE, the dose of VKA should be adjusted to maintain a target INR of 2.5 (range 2.0–3.0) regardless of treatment duration.''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}


===[[European society of cardiology#Classes of Recommendations|Class IIa]]===
{| class="wikitable"
'''7.''' For patients with PE and cancer, LMWH should be considered for the first 3–6 months ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' after this period, anticoagulant therapy with VKA or LMWH should be continued indefinitely or until the cancer is considered cured. ''([[European society of cardiology#Classes of Recommendations|Class I]],[[European society of cardiology#Level of Evidence|Level of Evidence: C]])}}''
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIb]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Patients with a first episode of unprovoked PE and low risk of bleeding, and in whom stable anticoagulation can be achieved, may be considered for long-term oral anticoagulation. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


==Guidelines Resources==
{| class="wikitable"
*Guidelines on the diagnosis and management of acute pulmonary embolism<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |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=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>.
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[European society of cardiology#Classes of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' For patients with PE and cancer, LMWH should be considered for the first 3–6 months ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' after this period, anticoagulant therapy with VKA or LMWH should be continued indefinitely or until the cancer is considered cured.''([[European society of cardiology#Classes of Recommendations|Class I]],[[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}


==References==
==References==
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Latest revision as of 23:53, 29 July 2020



Resident
Survival
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Pulmonary Embolism Microchapters

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Risk calculators and risk factors for Pulmonary embolism medical therapy

Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Rim Halaby, M.D. [3]

For the algorithms about the treatment choices, click here.

Overview

Medical therapy for pulmonary embolism (PE) includes anticoagulation therapy and fibrinolytic therapy. Parenteral anticoagulation therapy with either unfractionated heparin, low molecular weight heparin (LMWH), or fondaparinux is indicated in the initial treatment of patients with PE who do not have any contraindications for anticoagulation. Initial parenteral anticoagulation therapy should be started before the completion of the diagnostic workup among patients who have a high pretest probability of PE as well as among those with intermediate pretest probability of PE and an expected delay in the diagnostic results of more than 4 hours.[1] Thrombolytic therapy is indicated for the treatment of massive PE, also known as high-risk PE.[2] Patients with PE require long term anticoagulation therapy with agents such as vitamin K antagonists, LMWH, dabigatran, or rivaroxaban.

The need for treatment of subsegmental pulmonary emboli is uncertain.[3]

Anticoagulation Therapy

  • The most common cause of mortality in patients with a PE, is a recurrent PE occurring within a few hours of the initial event.[4] Anticoagulation is the cornerstone of therapy in an acute PE. Anticoagulation prevents further clot formation and extension, therefore it should be started as early as possible. Anticoagulation does not disaggregate existing clot, but it does facilitate the action of the body's endogenous lytic system.[4][5]
  • Certain conditions like pericardial tamponade and aortic dissection can mimic pulmonary embolism. The use of anticoagulants is contraindicated in these medical conditions. Proceed with caution if these conditions are high on the differential.
  • Anticoagulation therapy can be either parenteral or oral.

Parenteral Anticoagulation Therapy

Heparin

  • Heparin binds to the enzyme inhibitor antithrombin III (AT). The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa.

Heparin Dosage

Shown below is a table depicting the dosage of heparin for the treatment of pulmonary embolism. Note that the dose of heparin used in the treatment of acute coronary syndrome is lower than that used for the treatment of PE.[1]

Mode of administration of Heparin Dosage
IV injection 80 U/kg as bolus, followed by 18 U/kg/h, OR

70 U/kg as bolus, followed by 15 U/kg/h for stroke or cardiac patients[6]

SC injection 333 U/kg as bolus, followed by 250 U/kg[6]

Adjustment of Heparin Dosage According to aPTT

aPTT should be monitored during treatment with Heparin. Prolongation of apTT correlates with an elevated serum concentration of heparin and requires adjustment of the dosage. Shown below is a table depicting the variation in the dosage according the aPTT.

aPTT Variation in the dosage[7]
< 1.2 x control (<35 s) Bolus: 80 U/kg
Infusion rate: increase by 4 U/kg/h
1.2-1.5 x control (35-45 s) Bolus: 40 U/kg
Infusion rate: increase by 2 U/kg/h
1.5-2.3 x control (46-70 s) Continue the same dosage
2.3-3.0 x control (71-90 s) Infusion rate: decrease by 2 U/kg/h
> 3.0 x control (>90s) Stop infusion for a period of 1 hour, then
Infusion rate: decrease by 3 U/kg/h

Platelet Monitoring

Among patients started on heparin, if the risk of heparin induced thrombocytopenia is more than 1%, monitor platelet count every 2 to 3 days from the 4th until the 14th day of treatment or until the discontinuation of heparin.[2]

Low Molecular Weight Heparin

  • LMWH is used as a first line therapy for the initial anticoagulation therapy for PE among patients with non-high risk PE.[1]
  • In addition, LMWH can also be used for the long term anticoagulation treatment for PE, but vitamin K antagonist are recommended as first line therapy. However, among cancer patients with provoked PE, LMWH is the first line therapy for the long term anticoagulation treatment.[1] LMWH is preferred in pregnancy to avoid the known teratogenic effects of warfarin.
  • LMWH is administered subcutaneously and does not require routine coagulation monitoring.
  • The recommended doses for treatment of PE are:[1]
    • Enoxaparin : 1 mg/Kg body weight (twice daily) OR 1.5 mg/kg once daily
    • Tinzaparin : 175 U/Kg body weight (once daily)

Fondaparinux

  • Fondaparinux is used as a first line therapy for the initial anticoagulation therapy for PE among patients with non-high risk PE. The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of factor Xa. Fondaparinux does not require routine coagulation monitoring.
  • Recommended doses for the treatment of PE depend on the weight of the patient:
    • Weight <50 Kg: 5 mg (once daily)
    • Weight between 50 Kg to 100 Kg: 7.5 mg (once daily)
    • Weight >100 Kg: 10 mg (once daily)

Oral Anticoagulation Therapy

Vitamin K Antagonist

  • Warfarin should not be administered in pregnancy and LMWH should be use instead.
  • Warfarin should be started as soon as possible following the initiation of parenteral anticoagulation therapy, preferably at the same day. Parenteral anticoagulation therapy should be continued for at least 5 days concomitantly with warfarin until INR reaches 2.[2]
  • Warfarin is administered as follows:
    • Begin with 5 mg warfarin for 2 days followed by dosing based on the INR.
    • Target INR is 2-3.
    • Monitor INR monthly.
    • If the INR is stable but there is one value 0.5 below or above the target range, continue the same dose and repeat INR within 1-2 weeks.
  • NSAIDs, COX2 selective NSAIDs and some antibiotics should be avoided when warfarin is administered.[6]

Factor X Inhibitors

Rivaroxaban is an oral factor X inhibitors that can be used in the long term treatment of PE.

Direct Thrombin Inhibitors

Dabigatran is an oral direct thrombin inhibitors that can be used in the long term treatment of PE.

Thrombolysis

Thrombolysis, also known as clot busting, is the breakdown of blood clots by pharmacological agents. Thrombolytic agents activate the enzyme plasminogen into plasmin which is responsible for the breakdown of fibrin. The thrombolytic agents that are FDA approved are: streptokinase, urokinase, and alteplase.[8]

Indications

  • Thrombolytic therapy is indicated for the treatment of massive PE, also known as high-risk PE.[2]
  • Thrombolytic therapy is currently not indicated for the treatment of submassive PE, also known as intermediate-risk PE. Patients with intermediate-risk PE have evidence of right ventricular dysfunction or myocardial necrosis in the absence of hypotension. According to the The Pulmonary Embolism Thrombolysis (PEITHO) trial, fibrinolytic therapy in intermediate-risk PE decreased the rate of the compensation of the hemodynamic status at an expense of an elevated rate of major hemorrhage and stroke.[9] A recent metaanalysis of 16 randomized clinical trials of 2115 PE patients, 70.87% of whom are intermediate-risk patients, revealed that thrombolytic therapy in PE is associated with a decreased rate of mortality and an increase rate of major bleed and intracranial hemorrhage, particularly among patients who are older than 65 years.[10]
  • When patients initially classified as intermediate-risk fail to improve, or develop cardiogenic shock, hypotension (<90 mmHg), or respiratory distress (SaO2<95% with Borg score>8 or altered mental status), they should be administered fibrinolytic therapy.[8]

Dosage

Shown below is the dosage schedule for the thrombolytic agents:[8]

  • Streptokinase (FDA-approved)
    • Loading dose: 250 000 IU over 30 min
    • Maintenance dose: 100 000 IU/h over 12–24 hr
    • Accelerated regimen: 1.5 million IU over 2 hr
  • Urokinase (FDA-approved)
    • Loading dose: 4400 IU/kg over 10 min
    • Maintenance dose: 4400 IU/kg/h over 12–24 hr
    • Accelerated regimen: 3 million IU over 2 hr
  • Recombinant tissue plasminogen activator (rtPA)[11]
    • Alteplase (FDA-approved): 10-mg IV bolus followed by 90 mg IV infusion over 2 hours
    • Reteplase: 10-U IV bolus followed in 30 mins by another 10-U IV bolus
    • Tenecteplase: 0.5-mg/kg IV bolus (max 50mg)

Administration

  • When indicated, fibrinolytic therapy should be administered for a short infusion time (for 2 hours) rather than over prolonged perfusion (for 24 hours).[2]
  • Anticoagulation therapy should be withheld during the 2 hours of fibrinolytic infusion.

Systemic Fibrinolysis vs Ultrasound Assisted Catheter Directed Thrombolysis

Fibrinolysis in PE can be achieved either by the systemic administration of fibrinolytic agents or by ultrasound-assisted catheter-directed thrombolysis. Catheter-directed thrombolysis has been reported to improve the right ventricular function among patients with submassive PE.[12] In fact, The Ultrasound Accelerated Thrombolysis of Pulmonary Embolism (ULTIMA) trial, a randomized controlled trial of 59 patients with intermediate risk PE, demonstrated that catheter-directed thrombolysis with a low dose <20mg rt-PA was superior to anticoagulation (heparin alone) in improving the right ventricular function without an increase in bleeding.[13] The advantage of catheter-directed thrombolysis compared to systemic thrombolysis is a less bleeding rate; however, catheter-directed thrombolysis requires extensive resources and expertise. Large scale clinical trials are needed to compare catheter-directed thrombolysis vs systemic fibrinolysis as well as catheter-directed thrombolysis vs anticoagulation therapy.

Contraindications

Shown below is a table summarizing the absolute and relative contraindications to fibrinolytic therapy among pulmonary embolism patients.[7]

Absolute contraindications Relative contraindications
❑ Previous hemorrhagic stroke or stroke of unknown origin

Ischemic stroke within the last 6 months
Central nervous system tumor or damage
❑ Major trauma, head injury, or surgery within the last 3 weeks
Gastrointestinal bleed within the last month
❑ Known bleeding

Transient ischemic attack within the last 6 months

Oral anticoagulant therapy intake
❑ Advanced liver disease
Infective endocarditis
Peptic ulcer disease that is currently active
Pregnancy or within 1 week post partum
❑ Punctures that are non-compressible
Traumatic resuscitation
Systolic blood pressure >180 mmHg refractory to treatment

Complications of Thrombolytic Therapy

Contraindicated medications

Pulmonary embolism is considered an absolute contraindication to the use of the following medications:

2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis (DO NOT EDIT)[2]

Recommendations for Initial Treatment of Acute PE

Class I
"1. In patients with acute PE, we recommend initial treatment with parenteral anticoagulation (LMWH, fondaparinux, IV UFH, or SC UFH) over no such initial treatment. (Level of Evidence: B)"
"2. In patients with acute PE, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the INR is 2.0 or above for at least 24 h. (Level of Evidence: B)"
"3. In patients with acute PE who are treated with anticoagulants, we recommend against the use of an IVC filter. (Level of Evidence: B)"
"4. In patients with acute PE and contraindication to anticoagulation, we recommend the use of an IVC filter. (Level of Evidence: B)"
"5. In most patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy. (Level of Evidence: C)"
Class II
"1. In patients with low-risk PE and whose home circumstances are adequate, we suggest early discharge over standard discharge (eg,after the first 5 days of treatment). (Level of Evidence: B)"
"2. In patients with acute PE and an IVC filter inserted as an alternative to anticoagulation, we suggest a conventional course of anticoagulant therapy if their risk of bleeding resolves. (Level of Evidence: B)"
"3. In patients with a high clinical suspicion of acute PE, we suggest treatment with parenteral anticoagulants compared with no treatment while awaiting the results of diagnostic tests. (Level of Evidence: C)"
"4. In patients with an intermediate clinical suspicion of acute PE, we suggest treatment with parenteral anticoagulants compared with no treatment if the results of diagnostic tests are expected to be delayed for more than 4 h. (Level of Evidence: C)"
"5. In patients with a low clinical suspicion of acute PE, we suggest not treating with parenteral anticoagulants while awaiting the results of diagnostic tests provided that test results are expected within 24 h. (Level of Evidence: C)"
"6. In patients with acute PE, we suggest LMWH or fondaparinux over IV UFH (Level of Evidence: C for LMWH); Level of Evidence: B for fondaparinux) , and over SC UFH (Level of Evidence: B for LMWH; Level of Evidence: C for fondaparinux)."
"7. In patients with acute PE treated with LMWH, we suggest once- over twice-daily administration. (Level of Evidence: C)"
"8. In patients with acute PE associated with hypotension (eg, systolic BP , 90 mm Hg) who do not have a high risk of bleeding, we suggest systemically administered thrombolytic therapy over no such therapy. (Level of Evidence: C)"
"9. In selected patients with acute PE not associated with hypotension and with a low risk of bleeding whose initial clinical presentation or clinical course after starting anticoagulant therapy suggests a high risk of developing hypotension, we suggest administration of thrombolytic therapy. (Level of Evidence: C)"
"10. In patients with acute PE, when a thrombolytic agent is used, we suggest short infusion times (eg, a 2-h infusion) over prolonged infusion times (eg, a 24-h infusion). (Level of Evidence: C)"
"11. In patients with acute PE, when a thrombolytic agent is used, we suggest administration through a peripheral vein over a pulmonary artery catheter. (Level of Evidence: C)"
"12. In patients with acute PE associated with hypotension and who have (i) contraindications to thrombolysis, (ii) failed thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter-assisted thrombus removal over no such intervention. (Level of Evidence: C)"
"13. In patients with acute PE associated with hypotension, we suggest surgical pulmonary embolectomy over no such intervention if they have (i) contraindications to thrombolysis, (ii) failed thrombolysis or catheter-assisted embolectomy, or (iii) shock that is likely to cause death before thrombolysis can take effect (e.g., within hours), provided surgical expertise and resources are available. (Level of Evidence: C)"

2012 ACCP Guidelines - Recommendations for Long-term Treatment of PE (DO NOT EDIT)[2]

Class I
"1. In patients with PE provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period, (ii) treatment of a longer time limited period (eg, 6 or 12 months), or (iii) extended therapy (regardless of bleeding risk). (Level of Evidence: B)"
"2. In patients with PE provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period, (ii) treatment of a longer time-limited period (eg, 6 or 12 months), and (iii) extended therapy if there is a high bleeding risk(Level of Evidence: B). We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Class II, Level of Evidence B)."
"3. In patients with an unprovoked PE, we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration. After 3 months of treatment, patients with unprovoked PE should be evaluated for the risk-benefit ratio of extended therapy. (Level of Evidence: B)"
"4. In patients with a second unprovoked VTE, we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk (Level of Evidence: B), and we suggest extended anticoagulant therapy in those with a moderate bleeding risk (Class II, Level of Evidence B)."
"5. In patients with a first VTE that is an unprovoked PE and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy. (Level of Evidence: B)"
"6. In patients with PE who are treated with VKA, we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) over a lower (INR < 2.0) or higher (INR 3.0-5.0) range for all treatment durations. (Level of Evidence: B)"
"7. In patients with PE and active cancer, if there is a low or moderate bleeding risk, we recommend extended anticoagulant therapy over 3 months of therapy (Level of Evidence: B), and if there is a high bleeding risk, we suggest extended anticoagulant therapy (Class II, Level of Evidence B)."
Class II
"1. In patients with a first VTE that is an unprovoked PE and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy. (Level of Evidence: B)"
"2. In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of therapy over extended therapy. (Level of Evidence: B)"
"3. In patients with PE and no cancer, we suggest VKA therapy over LMWH for long-term therapy. For patients with PE and no cancer who are not treated with VKA therapy, we suggest LMWH over dabigatran or rivaroxaban for long-term therapy. (Level of Evidence: C)"
"4. In patients with PE and cancer, we suggest LMWH over VKA therapy (Level of Evidence: B). In patients with PE and cancer who are not treated with LMWH, we suggest VKA over dabigatran or rivaroxaban for long-term therapy. (Level of Evidence: C)"
"5. In patients with PE who receive extended therapy, we suggest treatment with the same anticoagulant chosen for the first 3 months. (Level of Evidence: C)"
"6. In patients who are incidentally found to have asymptomatic PE, we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic PE. (Level of Evidence: B)"

2012 ACCP Guidelines - Recommendations for Anticoagulation in Chronic Thromboembolic Pulmonary Hypertenion (DO NOT EDIT)[2]

Class I
"1. In patients with chronic thromboembolic pulmonary hypertension, we recommend extended anticoagulation over stopping therapy. (Level of Evidence: B)"
Class II
"1. In selected patients with chronic thromboembolic pulmonary hypertension, such as those with central disease under the care of an experienced throm boendarterectomy team, we suggest pulmonary thromboendarterectomy over no pulmonary thromboendarterectomy. (Level of Evidence: C) "

2011 AHA Scientific Statement- Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension (DO NOT EDIT)[8]

2011 ACC/AHA Guidelines- Recommendations for Initial Anticoagulation for Acute PE (DO NOT EDIT)[8]

Class I
"1. Therapeutic anticoagulation with subcutaneous LMWH, intravenous or subcutaneous UFH with monitoring, unmonitored weight-based subcutaneous UFH, or subcutaneous fondaparinux should be given to patients with objectively confirmed PE and no contraindications to anticoagulation (Level of Evidence: A). "
"2. Therapeutic anticoagulation during the diagnostic workup should be given to patients with intermediate or high clinical probability of PE and no contraindications to anticoagulation (Level of Evidence: C). "

2011 ACC/AHA Guidelines- Recommendations for Fibrinolysis for Acute PE (DO NOT EDIT)[8]

Class I
"1. All patients should be risk stratified. (Level of Evidence: C)"
"2. For most patients (stable) thrombolytic therapy not indicated. (Level of Evidence: B)"
"3. For unstable patients, thrombolytic therapy should be used unless major contraindications. (Level of Evidence: B)"
"4. Systemic therapy preferred over catheter directed lysis. (Level of Evidence: B)"
"5. Short infusions times ( nearly 2 hours) are preferred. (Level of Evidence: B)"
Class III (No Benefit)
"1. Fibrinolysis is not recommended for patients with low-risk PE or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening(Level of Evidence: B). "
"2. Fibrinolysis is not recommended for undifferentiated cardiac arrest(Level of Evidence: B). "
Class IIa
"1. Fibrinolysis is reasonable for patients with massive acute PE and acceptable risk of bleeding complications. (Level of Evidence: B) "
Class IIb
"1. Fibrinolysis may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory insufficiency, severe RV dysfunction, or major myocardial necrosis) and low risk of bleeding complications(Level of Evidence: C)."

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)(DO NOT EDIT)[7]

Treatment of High-Risk Pulmonary Embolism (DO NOT EDIT)[7]

Class I
"1. Anticoagulation with unfractionated heparin should be initiated without delay in patients with high-risk PE. (Level of Evidence: A) "
"2. Systemic hypotension should be corrected to prevent progression of RV failure and death due to PE. (Level of Evidence: C)"
"3. Vasopressive drugs are recommended for hypotensive patients with PE. (Level of Evidence: C)"
"4. Oxygen should be administered in patients with hypoxaemia.(Level of Evidence: C)"
"5. Thrombolytic therapy should be used in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension.(Level of Evidence: A)"
"6. Surgical pulmonary embolectomy is a recommended therapeutic alternative in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed.(Level of Evidence: C)"
Class III
"1. Aggressive fluid challenge is not recommended. (Level of Evidence: B)"
Class IIa
"1. Dobutamine and dopamine may be used in patients with PE, low cardiac output and normal blood pressure. (Level of Evidence: B)"
Class IIb
"1.Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk patients when thrombolysis is absolutely contraindicated or has failed. (Level of Evidence: C)"

Treatment of Non-High-Risk Pulmonary Embolism (DO NOT EDIT)[7]

Class I
"1. Anticoagulation should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic workup is still ongoing. (Level of Evidence: C)"
"2. Use of LMWH or fondaparinux is the recommended form of initial treatment for most patients with non-high-risk PE. (Level of Evidence: A) "
"3. In patients at high risk of bleeding and in those with severe renal dysfunction, unfractionated heparin with an aPTT target range of 1.5–2.5 times normal is a recommended form of initial treatment. (Level of Evidence: C) "
"4. Initial treatment with unfractionated heparin, LMWH or fondaparinux should be continued for at least 5 days and (Level of Evidence: A) may be replaced by vitamin K antagonists only after achieving target INR levels for at least 2 consecutive days (Level of Evidence: C)"
Class III
"1. Thrombolytic therapy should be not used in patients with low-risk PE (Level of Evidence: B) "
Class IIb
"1. Routine use of thrombolysis in non–high-risk PE patients is not recommended, but it may be considered in selected patients with intermediate-risk PE (Level of Evidence: B) "

Recommendations Long-Term Treatment (DO NOT EDIT)[7]

Class I
"1. For patients with PE secondary to a transient (reversible) risk factor, treatment with a VKA is recommended for 3 months.(Level of Evidence: A)"
"2. For patients with unprovoked PE, treatment with a VKA is recommended for at least 3 months. (Level of Evidence: A)"
"3. For patients with a second episode of unprovoked PE, long-term treatment is recommended. (Level of Evidence: A)"
"4. In patients who receive long-term anticoagulant treatment, the risk/benefit ratio of continuing such treatment should be reassessed at regular intervals. (Level of Evidence: C)"
"5. In patients with PE, the dose of VKA should be adjusted to maintain a target INR of 2.5 (range 2.0–3.0) regardless of treatment duration.(Level of Evidence: A)"
Class IIb
"1. Patients with a first episode of unprovoked PE and low risk of bleeding, and in whom stable anticoagulation can be achieved, may be considered for long-term oral anticoagulation. (Level of Evidence: B)"
Class IIa
"1. For patients with PE and cancer, LMWH should be considered for the first 3–6 months (Level of Evidence: B) after this period, anticoagulant therapy with VKA or LMWH should be continued indefinitely or until the cancer is considered cured.(Class I,Level of Evidence: C)"

References

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