Pulmonary embolism

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

high risk (massive) PE or high clinical probability of PE with shock or hypotension (i.e., systolic BP <90 mmHg), no contraindication to anticoagulation or thrombolysis

1st line – respiratory support

Back

1st line –

respiratory support

Supplemental high-concentration oxygen should be administered, targeting oxygen saturations of 94% to 98% (or 88% to 92% in patients at risk of hypercapnic respiratory failure).[213]

Intubation and mechanical ventilation may be necessary for patients with severe hypoxemia/respiratory failure. Mechanical ventilation can lead to hypotension, so blood pressure (BP) should be monitored closely.

Extracorporeal membrane oxygenation therapy (ECMO) therapy may be employed in patients with high risk PE, usually in conjunction with reperfusion therapies.[203]

Plus – intravenous fluids

Back

Plus –

intravenous fluids

Treatment recommended for ALL patients in selected patient group

If systolic BP is <90 mmHg, intravenous fluids should be given. Acute right ventricular failure with resulting low systemic output is the leading cause of death in patients with PE.[3]

Studies indicate that aggressive volume expansion is of no benefit, and may even worsen right ventricular function by causing mechanical overstretch, or by reflex mechanisms that depress contractility. However, modest fluid challenge (i.e., 500 mL crystalloid) may be of benefit in patients with PE, a low cardiac index, and normal BP.[217]

Plus – vasoactive agents

Back

Plus –

vasoactive agents

Treatment recommended for ALL patients in selected patient group

If systolic BP is <90 mmHg, vasopressors may be given in parallel with (or while waiting for) pharmacologic, surgical, or interventional reperfusion treatment.[3]

Norepinephrine (noradrenaline) may improve right ventricular function and right ventricular coronary perfusion.[3] Its use should probably be limited to hypotensive patients.[3]

Dobutamine enhances contractility with an increase in stroke volume and cardiac output. However, its systemic vasodilatory effect can lead to hypotension.[3]

Epinephrine (adrenaline) combines the beneficial properties of norepinephrine (vasoconstriction with increased right ventricular perfusion, positive inotropy) and dobutamine (positive inotropy), but without the vasodilatory effects associated with the latter.[218]

Primary options

norepinephrine: consult specialist for guidance on dose

dobutamine: consult specialist for guidance on dose

epinephrine (adrenaline): consult specialist for guidance on dose

Plus – initial parenteral anticoagulation

Back

Plus –

initial parenteral anticoagulation

Treatment recommended for ALL patients in selected patient group

For patients with high risk (massive) PE disease or high clinical probability of PE with shock or hypotension (i.e., systolic BP <90 mmHg), in whom interventional therapy is being planned or considered, intravenous unfractionated heparin (UFH) is preferred, as most studies of interventional therapies were performed with this anticoagulant. It can also be adjusted if needed during intervention and has a relatively short half-life if bleeding occurs.[3][19][250]

UFH is usually initiated with an intravenous weight-based loading bolus followed immediately by initiation of a weight-based continuous infusion. It also requires monitoring of activated partial thromboplastin time (aPTT) or heparin-calibrated anti-Xa activity, which is used to titrate dosing to the target range.

If PE is subsequently excluded, anticoagulation can be discontinued.[3][19][124]

Primary options

heparin: 80 units/kg intravenous bolus initially, followed by 18 units/kg/hour intravenous infusion, adjust dose according to aPTT; 333 units/kg subcutaneously initially, followed by 250 units/kg every 12 hours

Plus – switch to longer-term anticoagulation

Back

Plus –

switch to longer-term anticoagulation

Treatment recommended for ALL patients in selected patient group

Anticoagulation therapy should be continued following interventional therapy. Depending on the degree of concern for post-procedure bleeding, treatment with UFH may be resumed, followed by conversion to treatment-phase therapy when bleeding risk remits, or treatment-phase therapy can be started immediately. Choice of treatment-phase therapy is guided by the choice for the most appropriate longer term therapy. Generally, this will be a direct oral anticoagulant (DOAC), but there are exceptions for specific patient populations.

The choice of agent depends on patient factors such as hepatic function, renal function, pregnancy, presence of cancer, obesity, concomitant drugs the patient may be on and the ability to monitor drug-drug interactions, and the risk of bleeding. Choice may also depend on individual physician or patient preference or recommendations in local guidelines.[19]

DOACs (apixaban, edoxaban, rivaroxaban, dabigatran) are generally recommended over a vitamin K antagonist (usually warfarin). If a DOAC is chosen, there is either an initiation phase at a higher oral dose (apixaban and rivaroxaban), or lead-in treatment with a parenteral anticoagulant for 5-10 days while treatment is established (edoxaban and dabigatran). This is then followed by oral monotherapy at treatment-phase dosing of the chosen agent. DOACs are as effective as UFH, low molecular weight heparin (LMWH), and warfarin for the treatment of venous thromboembolism (VTE), and are generally recommended over these drugs outside of special populations.[238] No monitoring of coagulation profile is necessary, and bleeding complications are similar to those of warfarin, but there is a lower or similar incidence of VTE.[239][240] All have a longer half-life than UFH or LMWH and a shorter half-life than warfarin, and all have a rapid onset of action. DOACs do not interact with food; however, they do undergo some drug-drug interactions. Notable drug interactions include: strong inhibitors or inducers of P-glycoprotein (with edoxaban and dabigatran); and strong inhibitors or inducers of P-glycoprotein and CYP3A4 (with apixaban and rivaroxaban).

In patients who will transition from UFH to warfarin, UFH should be continued while treatment is established on warfarin, unless there is a very high risk for bleeding. If bleeding risk is high, observing the patient for 1-2 days on UFH alone is advisable. Three strategies can be used to select the initial dose of warfarin: a clinical algorithm calculates the estimated stable and starting dose based on several patient characteristics; a genetic algorithm calculates the estimated stable and starting dose based on the results of genetic tests such as CYP450-2C9 genotype and VKOR-C1 haplotype, as well as clinical variables; a fixed-dose approach uses initiation nomograms.[242][243] Once warfarin is started, it is continued concomitantly with the parenteral anticoagulant while the dose is titrated. Subsequent dosing of warfarin is based on the international normalized ratio (INR). The therapeutic INR range is 2-3 (target 2.5, unless concomitantly being used for anticoagulation of mechanical heart valves). UFH should be continued for a minimum of 5 days, and until INR is 2 or greater for at least 24 hours, at which point the parenteral anticoagulant can be discontinued.[19][249]

UFH is preferred when a short-acting agent is needed due to concerns about bleeding. Treatment requires monitoring of aPTT or heparin-calibrated anti-Xa activity, which is used to titrate dose to the target range. LMWH may be used if there are indications for extended LMWH (e.g., in patients who cannot take an oral drug, patients with cancer with concomitant drugs that have significant drug-drug interaction that precludes DOAC, patients with an intraluminal gastrointestinal (GI) malignancy and high risk of GI bleeding, and patients with severe liver disease where neither warfarin nor DOACs can be used). LMWH is dosed subcutaneously according to patient weight. Platelet count is regularly measured during treatment with UFH or LMWH because of the possibility of HIT as a complication.

Increased risk of bleeding: it may be preferable to treat patients who are at increased risk of bleeding (e.g., recent surgery, peptic ulceration) with intravenous UFH initially because it has a short half-life and its effect can be reversed quickly with protamine.[45] Once it is clear anticoagulation is tolerated, selection of an appropriate anticoagulation regimen can take place.

Active cancer: in patients with VTE and active cancer a DOAC (apixaban, edoxaban, rivaroxaban) is recommended over LMWH.[19][20] LMWH, UFH, fondaparinux, rivaroxaban, or apixaban can be used for initial anticoagulation.[46] DOACs (particularly edoxaban and rivaroxaban) are associated with a higher risk of GI bleeding than LMWH. In patients with luminal GI cancer, the American College of Chest Physicians (ACCP) recommends apixaban or LMWH as the preferred agents.[19][251]

Renal impairment: for patients with renal impairment (i.e., creatinine clearance <30 mL/minute), intravenous or subcutaneous UFH followed by warfarin, is the preferred anticoagulant regimen. Apixaban is approved for use in severe renal disease, and has outcomes similar to UFH followed by warfarin, and represents an alternative option.[252] LMWH has unpredictable renal clearance among patients with renal failure. For patients on LMWH, laboratory monitoring of the anticoagulant effect (i.e., by anti-factor Xa assay) is generally not necessary, but should be considered in patients with severe renal impairment and those with moderate renal impairment if LMWH use is prolonged (i.e., >10 days).[130][253] Fondaparinux, edoxaban, rivaroxaban, and dabigatran are generally not recommended in people with severe renal impairment, and patients with creatinine clearance <25 to 30 mL/minute were excluded from large randomized controlled trials. Apixaban, edoxaban, and rivaroxaban may be used in some patients with renal impairment; however, consult your local guidance as recommendations vary between countries.

Hepatic impairment: UFH or LMWH are recommended in these patients, and should be overlapped with warfarin unless cancer is present.[19] Warfarin should be used cautiously if the baseline INR is elevated; extended-duration LMWH may be preferred.[21][254] DOACs are generally not recommended in patients with hepatic impairment, especially those with moderate-to-severe impairment (Child-Pugh class B or C).[19][45]

Obesity: UFH or LMWH are options for the initiation phase of treatment in patients living with obesity. The use of actual body weight is appropriate when calculating the therapeutic dose in obese patients. Laboratory monitoring of the anticoagulant effect of LMWH (i.e., by anti-factor Xa assay) is generally not necessary, but should be considered in patients with class III obesity (body mass index [BMI] 40 or above).[21][84][253] There is no known weight limit for the use of DOACs; however, they have not been extensively studied in patients with extreme weights. The Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis recommends dabigatran and edoxaban are avoided in patients with BMI >40 kg/m² or weight >120 kg given the lack of clinical outcomes data. Rivaroxaban and apixaban can be considered in these patients.[255] Two large, retrospective, matched cohort studies showed similar outcomes in patients receiving rivaroxaban, apixaban, or dabigatran versus warfarin, though no prospective comparative evidence exists.[256][257] If DOACs are used in these patients, appropriate drug-specific monitoring may be considered, though there is limited evidence that drug-specific levels predict important clinical outcomes.[84]

Pregnancy: women who develop VTE and who are pregnant or may become pregnant can be treated with subcutaneous UFH or LMWH monotherapy.[258] Because of changes in the pharmacodynamics of subcutaneous UFH during pregnancy, LMWH is preferred.[19][259] Routine measurement of peak anti-Xa activity for pregnant or postpartum patients on LMWH is not recommended except in women at extremes of body weight (i.e., <50 kg or >90 kg) or with other complicating factors (e.g., renal impairment or recurrent VTE) that put them at high risk. Warfarin is known to cause teratogenic effects when used in pregnancy and should be avoided. If breast-feeding is planned, then LMWH is the agent of choice. Warfarin is an alternative; it is minimally secreted in breast milk, but there is extensive clinical experience suggesting no sick effect in the breast-feeding infant.[197][260] The safety of DOACs in pregnancy and lactation is not known, and they should be avoided in both situations (but can be used in the postpartum period if the patient is not breast-feeding).

Heparin-induced thrombocytopenia (HIT): in patients with HIT, anticoagulation is with argatroban. Fondaparinux, apixaban, rivaroxaban, and dabigatran have also been suggested, though they are not approved for patients with active HIT.[237][236] Argatroban is preferred for patients with HIT with high bleeding risk or renal impairment. See Heparin-induced thrombocytopenia (HIT).

Treatment-phase anticoagulation is recommended after the initial phase of anticoagulation. The American College of Chest Physicians (ACCP) guidelines recommend that patients who do not have a contraindication are given a 3-month treatment-phase of anticoagulation. DOACs are recommended over warfarin.[19][285] Once the treatment-phase has been completed, all patients should be evaluated for extended-phase therapy.[19][285] During the treatment-phase, follow-up and reevaluation are based on the patient’s level of risk for bleeding, comorbidities, and the anticoagulant agent selected.[19][285] Patients taking edoxaban or dabigatran should remain on the same dose started during the initiation phase unless renal function substantially declines, warranting discontinuation.[45][149] Apixaban and rivaroxaban doses should be adjusted following the initiation phase.[45] Patients treated with warfarin should continue to have INR monitoring. The frequency of measurements depends on the stability of INR values at each visit. Commonly, INR is measured once or twice weekly after initial dose titration, with the time between measurements progressively extending if values remain in range. The target range of 2-3 (target INR 2.5) is maintained, unless concomitantly being used for anticoagulation of mechanical heart valves.[45][149] If extended LMWH is used, the dose depends upon the agent. If dalteparin is chosen, the dose is reduced after 1 month. If enoxaparin is chosen, some experts suggest reducing the initial dose after 1 month though this is based on opinion only, and the initial dose can be continued. LMWH dose should be adjusted to change in the patient’s weight or creatinine clearance.

Primary options

Direct oral anticoagulant (DOAC)

apixaban: 10 mg orally twice daily for 7 days, followed by 5 mg twice daily

Direct oral anticoagulant (DOAC)

edoxaban: ≤60 kg body weight: 30 mg orally once daily, starting 5-10 days after treatment with a parenteral anticoagulant; >60 kg body weight: 60 mg orally once daily, starting 5-10 days after treatment with a parenteral anticoagulant

Direct oral anticoagulant (DOAC)

rivaroxaban: 15 mg orally twice daily initially for 21 days, followed by 20 mg once daily

Direct oral anticoagulant (DOAC)

dabigatran etexilate: 150 mg orally twice daily, starting 5-10 days after treatment with a parenteral anticoagulant

Vitamin K antagonist

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

Low molecular weight heparin (LMWH)

enoxaparin: 1 mg/kg subcutaneously every 12 hours; or 1.5 mg/kg subcutaneously every 24 hours

Low molecular weight heparin (LMWH)

dalteparin: 200 units/kg subcutaneously every 24 hours for 1 month, followed by 150 units/kg every 24 hours, maximum 18,000 units/day; or 100 units/kg subcutaneously every 12 hours for 1 month, followed by 150 units/kg every 24 hours, maximum 18,000 units/day

Unfractionated heparin (UFH)

Factor Xa inhibitor

fondaparinux: <50 kg body weight: 5 mg subcutaneously once daily; 50-100 kg body weight: 7.5 mg subcutaneously once daily; >100 kg body weight: 10 mg subcutaneously once daily

Direct thrombin inhibitor

argatroban: consult specialist for guidance on dose

Plus – thrombolysis or embolectomy or catheter-directed therapy

Back

Plus –

thrombolysis or embolectomy or catheter-directed therapy

Treatment recommended for ALL patients in selected patient group

Systemic thrombolytic therapy is recommended in patients with hemodynamic compromise (shock, systolic BP <90 mmHg, or vasopressor requirement to maintain systolic BP >90 mmHg), as this patient group has a high mortality rate.[3][19][22][124][219][220][221][222][223] The American College of Chest Physicians (ACCP) recommends systemic thrombolytic therapy (unless contraindicated) using a peripheral vein for patients with acute PE associated with hypotension who do not have a high bleeding risk. The The American College of Chest Physicians (ACCP) does not make specific recommendations on preferred agents due to lack of comparative data.[19]

Systemic thrombolytic therapy is associated with lower all-cause mortality than anticoagulation alone in patients with high-risk (massive) PE (acute PE with sustained hypotension [i.e., systolic BP <90 mmHg for at least 15 minutes]).[3][219][220][224]

Ideally, PE should be confirmed by imaging before thrombolytic therapy is administered.[124] However, if the patient is at risk of imminent cardiac arrest, treatment may be commenced on clinical grounds alone.[126]

Systemic thrombolytic therapy induces prompt clot dissolution and improves right ventricular function, pulmonary blood flow, and lung perfusion.[3][224] Thrombolysis plus heparin was associated with significantly reduced 30-day mortality compared with heparin alone (2.3% [24/1033] vs. 3.9% [40/1024], respectively; pooled odds ratio [OR] 0.59, 95% CI 0.36 to 0.96, P=0.03) in a meta-analysis of patients with acute PE.[224] Thrombolysis is associated with a significantly increased risk of major and minor bleeding, including hemorrhagic stroke.[219][220][224]

Absolute contraindications to thrombolysis include: hemorrhagic stroke or stroke of unknown origin at any time; ischemic stroke in the preceding 6 months; central nervous system damage or neoplasms; recent major trauma/surgery/head injury (in the preceding 3 weeks); GI bleeding within the last month; known bleeding risk.[3][219][225]

Relative contraindications to thrombolysis include: transient ischemic attack in the preceding 6 months; oral anticoagulant therapy; pregnancy, or within 1 week postpartum; traumatic resuscitation (in relation to this episode of PE); refractory hypertension (systolic BP >180 mmHg); advanced liver disease; infective endocarditis; active peptic ulcer.[3][225]

The preferred thrombolytic agents are alteplase or reteplase; tenecteplase is an alternative option.[221][222][223]

Systemic thrombolytic therapy increases bleeding risk, including that of intracranial bleeding.[19][224]

Surgical pulmonary embolectomy and catheter-directed therapy (which typically involves a either or a combination of mechanical and pharmacotherapeutic thrombus fragmentation) likely have lower attendant bleeding risk than systemic therapy.[3][19][212][226][227][228]

Surgical pulmonary embolectomy is recommended for patients in whom systemic thrombolytic therapy has failed or is absolutely contraindicated.[3][227]

Catheter-directed therapy may be considered for patients with acute PE associated with hypotension who also have a high bleeding risk, failed systemic thrombolysis, or shock that is likely to cause death before systemic thrombolysis can take effect (e.g., within hours), if appropriate expertise and resources are available.[19] Catheter-directed therapy uses a lower dose of thrombolytic drug and is believed to reduce the risks of bleeding at remote sites (e.g., intracranially or gastrointestinally).[19]

Primary options

alteplase: 100 mg intravenously given over 2 hours

reteplase: 10 units intravenously initially, followed by second dose of 10 units 30 minutes later

Secondary options

tenecteplase: consult specialist for guidance on dose

high risk or intermediate-high risk, contraindication to anticoagulation or thrombolysis

1st line – respiratory support

Back

1st line –

respiratory support

Supplemental high-concentration oxygen should be administered, targeting oxygen saturations of 94% to 98% (or 88% to 92% in patients at risk of hypercapnic respiratory failure).[213]

Intubation and mechanical ventilation may be necessary for patients with severe hypoxemia/respiratory failure. Mechanical ventilation can lead to hypotension, so BP should be monitored closely.

ECMO therapy may be employed in patients with high risk PE, usually in conjunction with reperfusion therapies.[203]

Plus – intravenous fluids

Back

Plus –

intravenous fluids

Treatment recommended for ALL patients in selected patient group

If systolic BP is <90 mmHg, intravenous fluids should be given. Acute right ventricular failure with resulting low systemic output is the leading cause of death in patients with PE.[3]

Plus – vasoactive agents

Back

Plus –

vasoactive agents

Treatment recommended for ALL patients in selected patient group

If systolic BP is <90 mmHg, vasopressors may be given in parallel with (or while waiting for) pharmacologic, surgical, or interventional reperfusion treatment.[3]

Norepinephrine (noradrenaline) may improve right ventricular function and right ventricular coronary perfusion.[3] Its use should probably be limited to hypotensive patients.[3]

Dobutamine enhances contractility with an increase in stroke volume and cardiac output. However, its systemic vasodilatory effect can lead to hypotension.[3]

Primary options

norepinephrine: consult specialist for guidance on dose

dobutamine: consult specialist for guidance on dose

epinephrine (adrenaline): consult specialist for guidance on dose

Plus – embolectomy and/or inferior vena cava filter

Back

Plus –

embolectomy and/or inferior vena cava filter

Treatment recommended for ALL patients in selected patient group

Surgical pulmonary embolectomy has lower attendant bleeding risk than systemic therapy.[3][19][212][226][227][228] It is recommended for patients in whom systemic thrombolytic therapy has failed or is absolutely contraindicated.[3][227]

ACCP guidelines recommend using an inferior vena cava (IVC) filter only for patients with acute PE (e.g., diagnosed in the preceding 1 month) and an absolute contraindication to anticoagulant therapy (e.g., active major bleeding, severe thrombocytopenia, high bleeding risk, central nervous system lesion).[19] Other guidelines consider relative indications for IVC filter use to include massive PE with residual DVT in a patient at risk for further PE, free-floating iliofemoral or IVC thrombus, and severe cardiopulmonary disease and deep vein thrombosis (DVT) (DVT; e.g., cor pulmonale with pulmonary hypertension).[269]

Some centers insert IVC filters intraoperatively or immediately postoperatively in patients who undergo surgical pulmonary embolectomy.[270][271][272]

IVC filter placement should take place as early as possible if it is the only treatment that can be initiated. There is little evidence available to suggest the ideal time for placement.

Observational studies suggest that insertion of a venous filter might reduce PE-related mortality rates in the acute phase but with an associated increase in the risk of filter-related VTE.[273][274]

Complications associated with permanent IVC filters are common, although they are rarely fatal.[274] Early complications (including insertion-site thrombosis) occur in approximately 10% of patients. Late complications are more frequent and include recurrent DVT (approximately 20% of patients) and post-thrombotic syndrome (up to 40% of patients).[275][276] Occlusion of the IVC affects approximately 22% of patients at 5 years and 33% at 9 years, regardless of the use and duration of anticoagulation.[276]

Post-filter anticoagulation should be considered on a case-by-case basis according to relative and absolute contraindications.[278] Anticoagulation should be initiated if the contraindication resolves or if a risk/benefit analysis suggests this to be a reasonable course.[19] When retrievable filters are used, they should be removed if anticoagulation has been instituted and once it is clearly being tolerated.[3]

intermediate-high risk PESI/sPESI score, no contraindication to anticoagulation or thrombolysis

1st line – respiratory support

Back

1st line –

respiratory support

Supplemental high-concentration oxygen should be administered, targeting oxygen saturations of 94% to 98% (or 88% to 92% in patients at risk of hypercapnic respiratory failure).[213]

Intubation and mechanical ventilation may be necessary for patients with severe hypoxemia/respiratory failure. Mechanical ventilation can lead to hypotension, so BP should be monitored closely.

ECMO therapy may be employed in patients with high risk PE, usually in conjunction with reperfusion therapies.[203]

Plus – anticoagulation

Back

Plus –

anticoagulation

Treatment recommended for ALL patients in selected patient group

Patients with confirmed PE without shock or hypotension require further risk stratification: for example with the Pulmonary Embolism Severity Index (PESI) or the simplified Pulmonary Embolism Severity Index (sPESI).[3][124] Patients with PESI risk stratification ≥III, or sPESI ≥1, with right ventricular dysfunction and a positive cardiac troponin test belong to an intermediate high-risk group.[3] These patients should receive an anticoagulant dosed according to the initiation phase of therapy, unless contraindicated.[3][19][235]

The choice of agent depends on patient factors such as hepatic function, renal function, pregnancy, presence of cancer, obesity, concomitant drugs and the ability to monitor drug-drug interactions, and the risk of bleeding. Choice may also depend on individual physician or patient preference or recommendations in local guidelines.[19]

In stable patients, the choice of initial anticoagulant is guided by the choice for the most appropriate longer term therapy. Generally, this will be a DOAC, but there are exceptions for specific patient populations.

If treatment was started before diagnostic confirmation and PE is subsequently excluded, anticoagulation can be discontinued. In patients with confirmed PE, anticoagulation should be adjusted to treatment-phase dose after completion of the initiation phase, and should continue for at least 3 months.[3][19][124]

DOACs (apixaban, edoxaban, rivaroxaban, dabigatran) are generally recommended over a vitamin K antagonist (usually warfarin). If a DOAC is chosen, there is either an initiation phase at a higher oral dose (apixaban and rivaroxaban), or lead-in treatment with a parenteral anticoagulant for 5-10 days while treatment is established (edoxaban and dabigatran). This is then followed by oral monotherapy at treatment-phase dosing of the chosen agent. DOACs are as effective as UFH, LMWH, and warfarin for the treatment of VTE, and are generally recommended over these drugs outside of special populations.[238] No monitoring of coagulation profile is necessary, and bleeding complications are similar to those of warfarin, but there is a lower or similar incidence of VTE.[239][240] All have a longer half-life than UFH or LMWH and a shorter half-life than warfarin, and all have a rapid onset of action. DOACs do not interact with food; however, they do undergo some drug-drug interactions. Notable drug interactions include: strong inhibitors or inducers of P-glycoprotein (with edoxaban and dabigatran); and strong inhibitors or inducers of P-glycoprotein and CYP3A4 (with apixaban and rivaroxaban).

In patients who will transition from UFH, LMWH or fondaparinux to warfarin, treatment with the initial agent should be continued while anticoagulation is established on warfarin, unless there is a very high risk for bleeding. If bleeding risk is high, observing the patient for 1-2 days on UFH alone is advisable. Three strategies can be used to select the initial dose of warfarin: a clinical algorithm calculates the estimated stable and starting dose based on several patient characteristics; a genetic algorithm calculates the estimated stable and starting dose based on the results of genetic tests such as CYP450-2C9 genotype and VKOR-C1 haplotype, as well as clinical variables; a fixed-dose approach uses initiation nomograms.[242][243] Once warfarin is started, it is continued concomitantly with the parenteral anticoagulant while the dose is titrated. Subsequent dosing of warfarin is based on the INR. The therapeutic INR range is 2-3 (target 2.5, unless concomitantly being used for anticoagulation of mechanical heart valves). UFH should be continued for a minimum of 5 days, and until INR is 2 or greater for at least 24 hours, at which point the parenteral anticoagulant can be discontinued.[19][249]

UFH is preferred when a short-acting agent is needed due to concerns about bleeding. Treatment requires monitoring of aPTT or heparin-calibrated anti-Xa activity, which is used to titrate dose to the target range. LMWH may be used in the initiation phase pending subsequent transition to a DOAC (dabigatran or edoxaban) or warfarin in the treatment-phase. LMWH is dosed subcutaneously according to patient weight. Platelet count is regularly measured during treatment with UFH or LMWH because of the possibility of HIT as a complication.

Obesity: UFH or LMWH are options for the initiation phase of treatment in patients living with obesity. The use of actual body weight is appropriate when calculating the therapeutic dose in obese patients. Laboratory monitoring of the anticoagulant effect of LMWH (i.e., by anti-factor Xa assay) is generally not necessary, but should be considered in patients with class III obesity (BMI 40 or above).[21][84][253] There is no known weight limit for the use of DOACs; however, they have not been extensively studied in patients with extreme weights. The Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis recommends dabigatran and edoxaban are avoided in patients with BMI >40 kg/m² or weight >120 kg given the lack of clinical outcomes data. Rivaroxaban and apixaban can be considered in these patients.[255] Two large, retrospective, matched cohort studies showed similar outcomes in patients receiving rivaroxaban, apixaban, or dabigatran versus warfarin, though no prospective comparative evidence exists.[256][257] If DOACs are used in these patients, appropriate drug-specific monitoring may be considered, though there is limited evidence that drug-specific levels predict important clinical outcomes.[84]

HIT: in patients with HIT, anticoagulation is with argatroban. Fondaparinux, apixaban, rivaroxaban, and dabigatran have also been suggested, though they are not approved for patients with active HIT.[237][236] Argatroban is preferred for patients with HIT with high bleeding risk or renal impairment. See Heparin-induced thrombocytopenia (HIT).

Primary options

Direct oral anticoagulant (DOAC)

apixaban: 10 mg orally twice daily for 7 days, followed by 5 mg twice daily

Direct oral anticoagulant (DOAC)

rivaroxaban: 15 mg orally twice daily initially for 21 days, followed by 20 mg once daily

Direct oral anticoagulant (DOAC)

dabigatran etexilate: 150 mg orally twice daily, starting 5-10 days after treatment with a parenteral anticoagulant

Vitamin K antagonist

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

Low molecular weight heparin (LMWH)

enoxaparin: 1 mg/kg subcutaneously every 12 hours; or 1.5 mg/kg subcutaneously every 24 hours

Low molecular weight heparin (LMWH)

Unfractionated heparin (UFH)

Factor Xa inhibitor

fondaparinux: <50 kg body weight: 5 mg subcutaneously once daily; 50-100 kg body weight: 7.5 mg subcutaneously once daily; >100 kg body weight: 10 mg subcutaneously once daily

Direct thrombin inhibitor

argatroban: consult specialist for guidance on dose

Consider – intravenous fluids

Back

Consider –

intravenous fluids

Treatment recommended for SOME patients in selected patient group

If systolic BP falls below 90 mmHg, intravenous fluids should be given. Acute right ventricular failure with resulting low systemic output is the leading cause of death in patients with PE.[3]

Studies indicate that aggressive volume expansion is of no benefit, and may even worsen right ventricular function by causing mechanical overstretch, or by reflex mechanisms that depress contractility. However, modest fluid challenge (i.e., 500 mL) may be of benefit in patients with PE, a low cardiac index, and normal BP.[217]

Consider – thrombolysis or embolectomy or catheter-directed therapy

Back

Consider –

thrombolysis or embolectomy or catheter-directed therapy

Treatment recommended for SOME patients in selected patient group

Patients with PESI risk stratification ≥III or sPESI ≥1 with right ventricular dysfunction and a positive cardiac troponin belong to an intermediate high-risk group.[3] Rescue thrombolysis may be indicated in intermediate high-risk patients, and in patients with other clinical features of cardiopulmonary impairment (e.g., elevated heart rate, respiratory rate, jugular venous pressure) who have started anticoagulant therapy, and: are deteriorating (as seen by a decrease in systolic BP, increase in heart rate, worsening gas exchange, signs of inadequate perfusion, worsening right ventricular function, or increasing cardiac biomarkers), but have not yet developed hypotension; are exhibiting signs of hemodynamic decompensation (e.g., systolic BP <90 mmHg for at least 15 minutes, or drop of systolic BP by at least 40 mmHg for at least 15 minutes with signs of end organ hypoperfusion).[3][19][212] Consideration of bleeding risk will inform choice of thrombolytic therapy.

Surgical pulmonary embolectomy and catheter-directed therapy (which typically involves a either or a combination of mechanical and pharmacotherapeutic thrombus fragmentation) have lower attendant bleeding risk than systemic therapy.[3][19][212][226][227][228]

Surgical pulmonary embolectomy is recommended for patients in whom systemic thrombolytic therapy has failed or is absolutely contraindicated.[3][227]

Catheter-directed therapy may be considered for patients with acute PE associated with hypotension who also have a high bleeding risk, failed systemic thrombolysis, or shock that is likely to cause death before systemic thrombolysis can take effect (e.g., within hours), if appropriate expertise and resources are available.[19] Catheter-directed therapy uses a lower dose of thrombolytic drug (approximately one third of full-dose systemic thrombolytic therapy) and is believed to reduce the risks of bleeding at remote sites (e.g., intracranially or gastrointestinally).[19]

Primary options

alteplase: 100 mg intravenously given over 2 hours

reteplase: 10 units intravenously initially, followed by second dose of 10 units 30 minutes later

Secondary options

tenecteplase: consult specialist for guidance on dose

intermediate-low risk or low risk PESI/sPESI score, no contraindication to anticoagulation

1st line – oxygen

Back

1st line –

oxygen

Supplemental high-concentration oxygen may be required. Target oxygen saturations of 94% to 98% (or 88% to 92% in patients at risk of hypercapnic respiratory failure).[213]

Plus – anticoagulation

Back

Plus –

anticoagulation

Treatment recommended for ALL patients in selected patient group

Patients with confirmed PE without shock or hypotension require further risk stratification: for example with the PESI or the sPESI.[3][124] Patients who present with suspected PE and an intermediate-low probability of disease (≥III, or sPESI ≥1 with normal echocardiogram and/or with negative cardiac biomarkers) or low probability of disease (PESI class I or II or sPESI score of 0) should receive an anticoagulant dosed according to the initiation phase of therapy, unless contraindicated.[3][19][235]

In stable patients the choice of initial anticoagulant is guided by the choice for the most appropriate longer term therapy. Generally, this will be a DOAC, but there are exceptions for specific patient populations.

DOACs (apixaban, edoxaban, rivaroxaban, dabigatran) are generally recommended over a vitamin K antagonist (usually warfarin). If a DOAC is chosen, there is either an initiation phase at a higher oral dose (apixaban and rivaroxaban), or lead-in treatment with a parenteral anticoagulant for 5-10 days while treatment is established (edoxaban and dabigatran). This is then followed by oral monotherapy at treatment-phase dosing of the chosen agent. DOACs are as effective as UFH, LMWH, and warfarin for the treatment of VTE, and are generally recommended over these drugs outside of special populations.[238] No monitoring of coagulation profile is necessary, and bleeding complications are similar to those of warfarin, but there is a lower or similar incidence of of VTE.[239][240] All have a longer half-life than UFH or LMWH and a shorter half-life than warfarin, and all have a rapid onset of action. DOACs do not interact with food; however, they do undergo some drug-drug interactions. Notable drug interactions include: strong inhibitors or inducers of P-glycoprotein (with edoxaban and dabigatran); and strong inhibitors or inducers of P-glycoprotein and CYP3A4 (with apixaban and rivaroxaban).

In patients who will transition from UFH, LMWH, or fondaparinux to warfarin, treatment with the initial agent should be continued while anticoagulation is established on warfarin, unless there is a very high risk for bleeding. If bleeding risk is high, observing the patient for 1-2 days on UFH alone is advisable. Three strategies can be used to select the initial dose of warfarin: a clinical algorithm calculates the estimated stable and starting dose based on several patient characteristics; a genetic algorithm calculates the estimated stable and starting dose based on the results of genetic tests such as CYP450-2C9 genotype and VKOR-C1 haplotype, as well as clinical variables; a fixed-dose approach uses initiation nomograms.[242][243] Once warfarin is started, it is continued concomitantly with the parenteral anticoagulant while the dose is titrated. Subsequent dosing of warfarin is based on the INR. The therapeutic INR range is 2-3 (target 2.5, unless concomitantly being used for anticoagulation of mechanical heart valves). UFH should be continued for a minimum of 5 days, and until INR is 2 or greater for at least 24 hours, at which point the parenteral anticoagulant can be discontinued.[19][249]

UFH is preferred when a short-acting agent is needed due to concerns about bleeding. Treatment requires monitoring of aPTT or heparin-calibrated anti-Xa activity, which is used to titrate dose to the target range. LMWH may be used in the initiation phase pending subsequent transition to a DOAC (dabigatran or edoxaban) or warfarin in the treatment-phase. LMWH is dosed subcutaneously according to patient weight. Platelet count is regularly measured during treatment with UFH or LMWH because of the possibility of HIT as a complication.

Obesity: UFH or LMWH are options for the initiation phase of treatment in patients living with obesity. The use of actual body weight is appropriate when calculating the therapeutic dose in obese patients. Laboratory monitoring of the anticoagulant effect of LMWH (i.e., by anti-factor Xa assay) is generally not necessary, but should be considered in patients with class III obesity (BMI 40 or above).[21][84][253] There is no known weight limit for the use of DOACs; however, they have not been extensively studied in patients with extreme weights. The Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis recommends dabigatran and edoxaban are avoided in patients with BMI >40 kg/m² or weight >120 kg given the lack of clinical outcomes data. Rivaroxaban and apixaban can be considered in these patients.[255] Two large, retrospective, matched cohort studies showed similar outcomes in patients receiving rivaroxaban, apixaban, or dabigatran versus warfarin, though no prospective comparative evidence exists.[256][257] If DOACs are used in these patients, appropriate drug-specific monitoring may be considered, though there is limited evidence that drug-specific levels predict important clinical outcomes.[84]

Primary options

Direct oral anticoagulant (DOAC)

apixaban: 10 mg orally twice daily for 7 days, followed by 5 mg twice daily

Direct oral anticoagulant (DOAC)

rivaroxaban: 15 mg orally twice daily initially for 21 days, followed by 20 mg once daily

Direct oral anticoagulant (DOAC)

dabigatran etexilate: 150 mg orally twice daily, starting 5-10 days after treatment with a parenteral anticoagulant

Vitamin K antagonist

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

Low molecular weight heparin (LMWH)

enoxaparin: 1 mg/kg subcutaneously every 12 hours; or 1.5 mg/kg subcutaneously every 24 hours

Low molecular weight heparin (LMWH)

Unfractionated heparin (UFH)

Factor Xa inhibitor

fondaparinux: <50 kg body weight: 5 mg subcutaneously once daily; 50-100 kg body weight: 7.5 mg subcutaneously once daily; >100 kg body weight: 10 mg subcutaneously once daily

Direct thrombin inhibitor

argatroban: consult specialist for guidance on dose

intermediate-low risk or low risk PESI/sPESI score, contraindication to anticoagulation

1st line – oxygen

Back

1st line –

oxygen

Supplemental high-concentration oxygen may be required. Target oxygen saturations of 94% to 98% (or 88% to 92% in patients at risk of hypercapnic respiratory failure).[213]

Plus – inferior vena cava filter

Back

Plus –

inferior vena cava filter

Treatment recommended for ALL patients in selected patient group

ACCP guidelines recommend using an inferior vena cava (IVC) filter only for patients with acute PE (e.g., diagnosed in the preceding 1 month) and an absolute contraindication to anticoagulant therapy (e.g., active major bleeding, severe thrombocytopenia, high bleeding risk, central nervous system lesion).[19] Other guidelines consider relative indications for IVC filter use to include massive PE with residual deep venous thrombus in a patient at risk for further PE, free-floating iliofemoral or IVC thrombus, and severe cardiopulmonary disease and DVT (DVT; e.g., cor pulmonale with pulmonary hypertension).[269]

IVC filter placement should take place as early as possible if it is the only treatment that can be initiated. There is little evidence available to suggest the ideal time for placement.

Observational studies suggest that insertion of a venous filter might reduce PE-related mortality rates in the acute phase but with an associated increase in the risk of filter-related VTE.[273][274]

ONGOING

confirmed PE: provoked

1st line – consider extended anticoagulation

Back

1st line –

consider extended anticoagulation

The goal for continuation of anticoagulant therapy into the extended phase (beyond the first 3 months and with no scheduled stop date) is secondary prevention of recurrent VTE.

The American College of Chest Physicians (ACCP) guidelines recommend that patients diagnosed with PE provoked by a persistent risk factor) are given extended-phase anticoagulation.[19][285] These patients should be given a DOAC, unless contraindicated, in which case they should be given a vitamin K antagonist (usually warfarin). Extended-phase anticoagulation is not recommended in patients with PE who are diagnosed in the context of a major or a minor transient risk factor.[19]

The American College of Chest Physicians (ACCP) guidelines recommend using reduced-dose apixaban or rivaroxaban for patients receiving apixaban or rivaroxaban; the choice of a particular drug and dose should consider the patient’s BMI, renal function, and adherence to the dosing regimen.[19] The decision to start or continue extended therapy should be based on patient preference and the predicted risk of recurrent VTE or bleeding.[19] The continued use of extended-phase anticoagulation should be reassessed at least annually, as well as at any time there is a significant change in the patient’s health status.[19]

For provoked (minor or major transient risk factors) PE, anticoagulation is discontinued after a course of at least 3 months. There is consensus that patients who have an index PE that occurs in the setting of a major transient provocation have a relatively low risk of developing recurrent VTE in the next 5 years, with estimates in the range of 15%.[19] In these patients, a time-limited course of anticoagulation of at least 3 months is suggested.[19]

The presence of a hereditary thrombophilia does not alter this recommendation, and guidelines recommend against testing for thrombophilias in patients with a PE occurring following a major transient provocation.[60]

The risk of recurrent VTE is modestly higher in patients who sustain PE in the setting of a minor transient provocation. Guidelines differ on offering extended anticoagulation for VTE associated with minor transient provoking risk factors.[22][250]

Primary options

apixaban: 5 mg orally twice daily; consider 2.5 mg orally twice daily after completing at least 6 months treatment

edoxaban: ≤60 kg body weight: 30 mg orally once daily; >60 kg body weight: 60 mg orally once daily

rivaroxaban: 20 mg orally once daily; consider 10 mg orally once daily after completing at least 6 months treatment

dabigatran etexilate: 150 mg orally twice daily

Secondary options

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

confirmed PE: unprovoked

1st line – extended anticoagulation or aspirin

Back

1st line –

extended anticoagulation or aspirin

The goal for continuation of anticoagulant therapy into the extended phase (i.e., beyond the first 3 months and with no scheduled stop date) is secondary prevention of VTE.

The American College of Chest Physicians (ACCP) guidelines recommend that patients diagnosed with PE in the absence of transient provocation (unprovoked PE) are given extended-phase anticoagulation.[19][285] These patients should be given a DOAC, unless contraindicated, in which case they should be given a vitamin K antagonist (usually warfarin).

For patients with a first PE that is unprovoked who have a low or moderate bleeding risk, extended anticoagulant therapy is recommended (with no scheduled stop date and reassessment of ongoing therapy at regular intervals, such as annually). For those patients with a high bleeding risk, 3 months’ treatment only is recommended. For patients with a second unprovoked PE who have a low or moderate bleeding risk, extended anticoagulant therapy is recommended (with no scheduled stop date) over 3 months' treatment. In patients with a high bleeding risk, 3 months’ treatment only is recommended.

Many studies have attempted to identify subgroups of patients with unprovoked VTE who do not need to be treated indefinitely with oral anticoagulation. There is strong evidence that the risk of recurrent VTE is higher in the following patients: male sex; those with a diagnosis of a proximal DVT (versus isolated calf DVT); those with ultrasound evidence of residual clot; those who have an elevated D-dimer 1 month after stopping a 3- to 6-month course of oral anticoagulation; and those who had an unprovoked DVT.[19][45] Several risk assessment models have been developed for this purpose, including the DASH score, the Vienna Prediction Model, and the “Men Continue and HER-DOO2” model.[261] The latter model identifies a subset of women with low risk for recurrent VTE after an initial unprovoked event, and one prospective validation study of this model was published.[262]

The continued use of extended-phase anticoagulation should be reassessed at least annually, as well as at any time there is a significant change in the patient’s health status.[19]

The evidence to continue extended therapy beyond 4 years is uncertain. The American College of Chest Physicians (ACCP) recommends shared decision-making, taking into account the patient’s values and preferences. Patients should be periodically reassessed for bleeding risk, burdens of therapy, and any change in values and preferences.[19]

If the decision is to stop extended-phase anticoagulation in patients with an unprovoked proximal PE, the American College of Chest Physicians (ACCP) guidelines recommend low-dose aspirin (unless contraindicated) to prevent recurrent VTE.[19][282][283] The benefits of using aspirin should be balanced against the risk of bleeding and inconvenience of use.[282][283] Aspirin should not, however, be considered a reasonable alternative for patients who are willing to undergo extended anticoagulation therapy, as aspirin is much less effective. The use of aspirin should in any case be reassessed when patients stop anticoagulant therapy because it might have been stopped when anticoagulant therapy was started.[19]

Primary options

apixaban: 5 mg orally twice daily; consider 2.5 mg orally twice daily after completing at least 6 months treatment

edoxaban: ≤60 kg body weight: 30 mg orally once daily; >60 kg body weight: 60 mg orally once daily

rivaroxaban: 20 mg orally once daily; consider 10 mg orally once daily after completing at least 6 months treatment

dabigatran etexilate: 150 mg orally twice daily

Secondary options

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

Tertiary options

aspirin: 81-100 mg orally once daily

confirmed PE: pregnant

1st line – extended anticoagulation

Back

1st line –

extended anticoagulation

The treatment/extended phase of anticoagulation differs in pregnant patients. Patients with pregnancy-associated VTE undergo treatment-phase anticoagulation for at least 3 months, or until 6 weeks postpartum, whichever is longer.[258][259] At the conclusion of this phase in the postpartum, decisions are made according to whether the patient is planning to breast-feed. Guidelines differ on offering extended anticoagulation for VTE associated with pregnancy, as there is an intermediate risk of future unprovoked VTE.[22][250]

Extended treatment with LMWH monotherapy is recommended in pregnant patients.[258]

Routine measurement of peak anti-Xa activity for pregnant or postpartum patients on LMWH is not recommended except in women at extremes of body weight (i.e., <50 kg or >90 kg) or with other complicating factors (e.g., renal impairment or recurrent VTE) that put them at high risk.

Warfarin is known to cause teratogenic effects when used in pregnancy and should be avoided.

If breast-feeding is planned, then LMWH is the agent of choice. Warfarin is an alternative; it is minimally secreted in breast milk, but there is extensive clinical experience suggesting no sick effect in the breast-feeding infant.[197][260]

Primary options

enoxaparin: 1 mg/kg subcutaneously every 12 hours

dalteparin: 200 units/kg subcutaneously every 24 hours once daily, maximum 18,000 units/dose; or 100 units/kg subcutaneously every 12 hours, maximum 18,000 units/dose

confirmed PE: cancer-associated

1st line – extended anticoagulation

Back

1st line –

extended anticoagulation

Cancer represents a persistent provocation for VTE until cured. Among patients who are diagnosed with PE and have an active cancer (e.g., cancer under any form of active therapy or palliation) there is a very high risk for recurrent VTE and indefinite anticoagulation is recommended. Guidelines recommend using a DOAC (DOAC; apixaban, edoxaban, rivaroxaban) or LMWH for at least the initial 6 months of therapy.[19][20]

A DOAC (apixaban, edoxaban, rivaroxaban) or LMWH is the preferred agent for patients with a higher risk of bleeding, especially those with GI cancers. LMWH is preferred for those with potential drug-drug interactions with apixaban, rivaroxaban, or dabigatran.[19][251][263][264][265]

Primary options

apixaban: 5 mg orally twice daily; consider 2.5 mg orally twice daily after completing at least 6 months treatment

edoxaban: ≤60 kg body weight: 30 mg orally once daily; >60 kg body weight: 60 mg orally once daily

rivaroxaban: 20 mg orally once daily; consider 10 mg orally once daily after completing at least 6 months treatment

enoxaparin: 1 mg/kg subcutaneously every 12 hours; or 1.5 mg/kg subcutaneously every 24 hours

confirmed PE: recurrent PE while on anticoagulation

1st line – further investigation + switch to LMWH

Back

1st line –

further investigation + switch to LMWH

Recurrent VTE is unusual among patients receiving therapeutic-dose anticoagulant therapy, with the exception of cancer (7% to 9% on-therapy recurrence with LMWH).[3][19][284] In addition to definitively establishing the presence of recurrent PE, consideration should be given to compliance with anticoagulant therapy or the presence of underlying malignancy.[19]

American College of Chest Physicians (ACCP) guidelines recommend a temporary switch to LMWH (for at least 1 month) for patients with recurrent PE who are thought to be compliant with a non-LMWH anticoagulant (or within the therapeutic range if receiving a vitamin K antagonist (usually warfarin).[19] An increased dose of LMWH (one quarter to one third) is appropriate for patients with recurrent PE who have been receiving LMWH.[19]

For patients who are no longer receiving anticoagulant therapy and experience a second PE with no identifiable risk factors (i.e., unprovoked, guidelines recommend the following anticoagulant treatment durations: low or moderate bleeding risk: extended anticoagulant therapy with periodic reassessment to review risk-benefit ratio; high bleeding risk: 3 months.[3][19]

Primary options

enoxaparin: consult specialist for guidance on dose

dalteparin: consult specialist for guidance on dose

Consider – inferior vena cava filter

Back

Consider –

inferior vena cava filter

Treatment recommended for SOME patients in selected patient group

An inferior vena cava (IVC) filter can be placed in patients with confirmed recurrent PE despite adequate anticoagulation; however, direct evidence supporting this intervention is very limited.[3]

Complications associated with permanent IVC filters are common, although they are rarely fatal.[274] Overall, early complications (including insertion-site thrombosis) occur in approximately 10% of patients. Late complications are more frequent and include recurrent deep vein thrombosis (approximately 20% of patients) and post-thrombotic syndrome (up to 40% of patients).[275][276] Occlusion of the IVC affects approximately 22% of patients at 5 years and 33% at 9 years, regardless of the use and duration of anticoagulation.[276]

Use of this content is subject to our disclaimer

Pulmonary embolism

Treatment algorithm

high risk (massive) PE or high clinical probability of PE with shock or hypotension (i.e., systolic BP <90 mmHg), no contraindication to anticoagulation or thrombolysis

respiratory support

intravenous fluids

vasoactive agents

Primary options

initial parenteral anticoagulation

Primary options

switch to longer-term anticoagulation

Primary options

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Vitamin K antagonist

Low molecular weight heparin (LMWH)

Low molecular weight heparin (LMWH)

Unfractionated heparin (UFH)

Factor Xa inhibitor

Direct thrombin inhibitor

thrombolysis or embolectomy or catheter-directed therapy

Primary options

Secondary options

high risk or intermediate-high risk, contraindication to anticoagulation or thrombolysis

respiratory support

intravenous fluids

vasoactive agents

Primary options

embolectomy and/or inferior vena cava filter

intermediate-high risk PESI/sPESI score, no contraindication to anticoagulation or thrombolysis

respiratory support

anticoagulation

Primary options

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Vitamin K antagonist

Low molecular weight heparin (LMWH)

Low molecular weight heparin (LMWH)

Unfractionated heparin (UFH)

Factor Xa inhibitor

Direct thrombin inhibitor

intravenous fluids

thrombolysis or embolectomy or catheter-directed therapy

Primary options

Secondary options

intermediate-low risk or low risk PESI/sPESI score, no contraindication to anticoagulation

oxygen

anticoagulation

Primary options

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Direct oral anticoagulant (DOAC)

Vitamin K antagonist

Low molecular weight heparin (LMWH)

Low molecular weight heparin (LMWH)

Unfractionated heparin (UFH)

Factor Xa inhibitor

Direct thrombin inhibitor

intermediate-low risk or low risk PESI/sPESI score, contraindication to anticoagulation

oxygen

inferior vena cava filter

confirmed PE: provoked

consider extended anticoagulation

Primary options

Secondary options

confirmed PE: unprovoked

extended anticoagulation or aspirin

Primary options

Secondary options

Tertiary options

confirmed PE: pregnant

extended anticoagulation

Primary options

confirmed PE: cancer-associated

extended anticoagulation

Primary options