Pulmonary embolism treatment approach

Jump to navigation Jump to search

Pulmonary Embolism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Pulmonary Embolism from other Diseases

Epidemiology and Demographics

Risk Factors

Triggers

Natural History, Complications and Prognosis

Diagnosis

Diagnostic criteria

Assessment of Clinical Probability and Risk Scores

Pulmonary Embolism Assessment of Probability of Subsequent VTE and Risk Scores

History and Symptoms

Physical Examination

Laboratory Findings

Arterial Blood Gas Analysis

D-dimer

Biomarkers

Electrocardiogram

Chest X Ray

Ventilation/Perfusion Scan

Echocardiography

Compression Ultrasonography

CT

MRI

Treatment

Treatment approach

Medical Therapy

IVC Filter

Pulmonary Embolectomy

Pulmonary Thromboendarterectomy

Discharge Care and Long Term Treatment

Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Follow-Up

Support group

Special Scenario

Pregnancy

Cancer

Trials

Landmark Trials

Case Studies

Case #1

Pulmonary embolism treatment approach On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Pulmonary embolism treatment approach

CDC on Pulmonary embolism treatment approach

Pulmonary embolism treatment approach in the news

Blogs on Pulmonary embolism treatment approach

Directions to Hospitals Treating Pulmonary embolism treatment approach

Risk calculators and risk factors for Pulmonary embolism treatment approach

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

Overview

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

Step 1: Confirm PE

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

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

Step 2: Initial Treatment

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

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

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

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

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

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

Anticoagulation Therapy

Initial Anticoagulation Therapy

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

Long Term Anticoagulation Therapy

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

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


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

Step 3: Long Term Treatment

  • After treatment in the hospital, the patient should continue anticoagulation treatment for 3 months if the PE is provoked by surgery or a nonsurgical transient risk factor.
  • An abnormal D-dimer level at the end of the treatment course might signal the need for continued treatment with anticoagulation for a first time unprovoked pulmonary embolus.[7]
  • Long-term treatment is usually recommended with vitamin K antagonists like warfarin, unless contraindicated or some special circumstances.
  • The recommended therapeutic INR range for patients with PE is 2.0-3.0.
  • Continued warfarin administration needs close monitoring. The patient should have an appointment with the "anticoagulation clinic" before leaving the hospital.

Extended Anticoagulation

Extended Treatment means extending the anticoagulation therapy beyond the first 3 months. It is recommended in the following scenarios:

  • For a pulmonary embolism that is unprovoked. The patient's risk should be re-evaluated at 3 months to consider whether or not extended therapy is warranted.
  • Active cancer.
  • Recurrent venous thromboembolism.
  • Chronic thrombembolic pulmonary hypertension.

Salient Features:

  • For extended therapy, the continued need for anticoagulation and the risk-benefit ratio should be re-evaluated at periodic intervals (eg, annually).
  • Patients with recurrent thromboembolic disease, with or without anticoagulation, should be evaluated for possible thrombophilias.

Specific Circumstances

Newer Anticoagulants

  • Dabigatran (direct thrombin inhibitor), Rivaroxaban (Factor Xa inhibitor), and other drugs in the same classes, provide an alternate option to warfarin/LMWH for treatment of PE.
  • Advantages include the availability of an oral formulation, no frequent monitoring requirement, a predictable effect profile, and few (known) drug interactions.
  • Disadvantages include the currently limited prospective trial data, the theoretical interaction with statins (as they are metabolized by the same CYP3A4 enzyme), and the risk of bleeding.

References

  1. 1.0 1.1 1.2 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P; et al. (2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)". Eur Heart J. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870.
  2. 2.0 2.1 2.2 Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ; et al. (2012). "Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e419S–94S. doi:10.1378/chest.11-2301. PMC 3278049. PMID 22315268.
  3. 3.0 3.1 3.2 3.3 3.4 Kucher N, Goldhaber SZ (2005). "Management of massive pulmonary embolism". Circulation. 112 (2): e28–32. doi:10.1161/CIRCULATIONAHA.105.551374. PMID 16009801.
  4. 4.0 4.1 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ; et al. (2011). "Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association". Circulation. 123 (16): 1788–830. doi:10.1161/CIR.0b013e318214914f. PMID 21422387.
  5. 5.0 5.1 Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ; et al. (2012). "Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e152S–84S. doi:10.1378/chest.11-2295. PMC 3278055. PMID 22315259.
  6. Hokusai-VTE Investigators. Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S; et al. (2013). "Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism". N Engl J Med. 369 (15): 1406–15. doi:10.1056/NEJMoa1306638. PMID 23991658. Review in: Ann Intern Med. 2014 Jan 21;160(2):JC4 Review in: Ann Intern Med. 2014 Mar 18;160(6):JC4
  7. Palareti G, Cosmi B, Legnani C; et al. (2006). "D-dimer testing to determine the duration of anticoagulation therapy". N. Engl. J. Med. 355 (17): 1780–9. doi:10.1056/NEJMoa054444. PMID 17065639.
  8. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M (2003). "Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer". N Engl J Med. 349 (2): 146–53. PMID 12853587.

Template:WH Template:WS