What is the management plan for a patient at high risk of pulmonary embolism (PE) or deep vein thrombosis (DVT) with an elevated PE/DVT index?

Management of High-Risk PE/DVT

For patients at high risk of PE or DVT (elevated PE/DVT index), initiate immediate risk stratification based on hemodynamic stability, followed by appropriate diagnostic workup and therapeutic anticoagulation without delay. 1

Initial Risk Stratification

Assess hemodynamic stability first to identify high-risk (massive) PE:

• High-risk PE is defined by shock (systolic BP <90 mmHg) or sustained hypotension (systolic BP drop ≥40 mmHg for >15 minutes), unexplained hypoxia, engorged neck veins, and often right ventricular gallop 1
• Intermediate-risk (submassive) PE presents with right ventricular dysfunction on echocardiography or elevated cardiac biomarkers (troponin, BNP/NT-proBNP) but without hemodynamic compromise 1
• Low-risk PE has normal hemodynamics, normal biomarkers, and no RV dysfunction 1

Diagnostic Approach Based on Clinical Probability

Use validated clinical prediction rules (Wells score or simplified assessment) to guide testing: 1

For Low Clinical Probability:

• Measure D-dimer using highly sensitive assay (ELISA or equivalent) 1
• Negative D-dimer excludes PE/DVT—no further testing needed 1
• If D-dimer positive, proceed to imaging (CTPA for PE, compression ultrasound for DVT) 1

For Intermediate Clinical Probability:

• D-dimer testing is appropriate; negative result with validated assay (Vidas ELISA, MDA latex) excludes PE 1
• Positive D-dimer requires definitive imaging 1

For High Clinical Probability:

• Do not perform D-dimer testing—proceed directly to imaging as negative result does not safely exclude PE even with highly sensitive assays 1
• CTPA is first-line for PE; compression ultrasound for DVT 1
• If proximal DVT confirmed on ultrasound in patient with suspected PE, this confirms VTE and treatment should proceed 1

Critical pitfall: Most patients with PE are breathless and/or tachypneic >20/min; in the absence of these findings, pleuritic chest pain or hemoptysis is usually due to another cause 1

Immediate Treatment Based on Risk Category

High-Risk (Massive) PE:

Administer systemic thrombolytic therapy immediately: 1

• Alteplase 50 mg IV bolus for deteriorating patients or cardiac arrest 1
• For stable patients with confirmed massive PE: alteplase 100 mg IV over 90 minutes (accelerated MI regimen) 1
• Follow thrombolysis with unfractionated heparin after 3 hours, preferably weight-adjusted 1
• Surgical pulmonary embolectomy if thrombolysis contraindicated or fails 1
• Contraindications to thrombolysis should be ignored in life-threatening PE 1

Intermediate-Risk (Submassive) PE:

Anticoagulation alone is preferred over routine thrombolysis: 1

• Initiate therapeutic anticoagulation immediately 1
• Monitor closely for hemodynamic deterioration 1
• Consider thrombolysis for younger patients at low bleeding risk who deteriorate 1
• Administer rescue thrombolytic therapy if hemodynamic deterioration occurs on anticoagulation 1

Low-Risk PE and Uncomplicated DVT:

Consider outpatient treatment over hospitalization: 1

• Outpatient management appropriate if patient not unduly breathless, no medical/social contraindications, and efficient protocol in place 1
• Use validated risk scores (PESI or simplified PESI) to identify low-risk PE patients suitable for home treatment 1
• This does not apply to patients requiring hospitalization for other conditions, limited home support, medication affordability issues, or poor compliance history 1

Anticoagulation Selection

For patients without hemodynamic instability, prefer direct oral anticoagulants (DOACs) over vitamin K antagonists: 1

First-Line Options:

• Rivaroxaban 15 mg PO twice daily for 21 days, then 20 mg once daily (no parenteral bridging required) 1, 2
• Apixaban 10 mg PO twice daily for 7 days, then 5 mg twice daily (no parenteral bridging required) 2
• Dabigatran or edoxaban require initial parenteral anticoagulation for at least 5 days 1

Parenteral Anticoagulation (when needed):

• Prefer LMWH or fondaparinux over unfractionated heparin 1
• Enoxaparin 1 mg/kg SC twice daily or 1.5 mg/kg once daily 1
• Fondaparinux: weight-based dosing (<50 kg = 5 mg; 50-100 kg = 7.5 mg; >100 kg = 10 mg once daily) 1
• Use unfractionated heparin (80 U/kg bolus, then 18 U/kg/hour) only if: hemodynamic instability, severe renal insufficiency (CrCl <30 mL/min), high bleeding risk, or morbid obesity 1

Warfarin (if DOAC not suitable):

• Overlap with parenteral anticoagulation until INR 2.0-3.0 for 24 hours 1, 3
• Target INR 2.5 (range 2.0-3.0) for all VTE treatment 1, 3

Do not use DOACs in: 1

• Severe renal impairment (CrCl <30 mL/min for most DOACs) 1
• Antiphospholipid antibody syndrome (use warfarin) 1
• Pregnancy or lactation (use LMWH) 1

Duration of Anticoagulation

Minimum 3 months therapeutic anticoagulation for all patients with PE/DVT: 1, 3

Discontinue After 3 Months:

• First PE/DVT provoked by major transient/reversible risk factor (surgery, trauma, immobilization) 1, 3

Continue Indefinitely:

• Recurrent unprovoked VTE (at least one previous episode not related to reversible risk factor) 1
• Unprovoked first VTE with low bleeding risk (consider after risk-benefit assessment) 1, 3
• Chronic persistent risk factors (active cancer, inflammatory bowel disease, antiphospholipid syndrome) 1
• Active cancer requires LMWH over oral anticoagulants 1

6-12 Months Treatment:

• First unprovoked VTE in patients with moderate bleeding risk 1, 3
• Documented thrombophilia (Factor V Leiden, prothrombin mutation, protein C/S deficiency) 3

Reassess bleeding risk, renal/hepatic function, and adherence at regular intervals for patients on extended anticoagulation 1

Special Considerations

Pregnancy: 1

• Use therapeutic fixed-dose LMWH based on early pregnancy weight 1
• Do not insert spinal/epidural needle within 24 hours of last LMWH dose 1
• Do not administer LMWH within 4 hours of epidural catheter removal 1

Anticoagulation Failure (recurrent VTE on treatment): 4, 5

• Switch to therapeutic-dose LMWH immediately 4, 5
• Verify medication adherence first (most common cause of apparent failure) 4, 5
• Assess renal/hepatic function and drug-drug interactions 4, 5
• Investigate underlying causes: cancer, antiphospholipid syndrome, thrombophilia 4, 5
• Do not simply increase DOAC dose or switch to another DOAC 5

Follow-up: 1

• Routinely re-evaluate patients 3-6 months after acute PE 1
• Refer symptomatic patients with persistent perfusion defects beyond 3 months to pulmonary hypertension/CTEPH expert center 1