What is the appropriate next step in treatment for a 65-year-old patient with hypertension, presenting with sharp left-sided chest pain, shortness of breath, and a filling defect in the left upper pulmonary artery on CT scan, consistent with a pulmonary embolism (PE)?

Immediate Anticoagulation for Confirmed Pulmonary Embolism

This patient requires immediate initiation of anticoagulation therapy with either a direct oral anticoagulant (DOAC) such as rivaroxaban or apixaban, or unfractionated heparin bridged to warfarin, given the confirmed pulmonary embolism on CT scan. 1

Risk Stratification

This patient presents with intermediate-risk PE based on the clinical presentation:

• Hemodynamically stable (no sustained hypotension requiring vasopressors) 1
• Evidence of right ventricular strain suggested by the S4 gallop and holosystolic murmur at apex (likely tricuspid regurgitation) 1
• Hypoxemia requiring supplemental oxygen (92% on 2L O2) 1
• No signs of cardiogenic shock 1

The presence of unilateral leg edema suggests concurrent deep vein thrombosis as the embolic source. 1

Recommended Anticoagulation Strategy

First-Line Option: Direct Oral Anticoagulants (DOACs)

NOACs (rivaroxaban or apixaban) are the recommended first-line anticoagulant for this patient because they offer simplified dosing without the need for parenteral bridging therapy and have demonstrated equivalent efficacy with potentially improved safety compared to warfarin. 1

Rivaroxaban dosing: 15 mg orally twice daily with food for 21 days, then 20 mg once daily with food for continued treatment 2

Apixaban dosing: 10 mg orally twice daily for 7 days, then 5 mg twice daily 1

Alternative Option: Unfractionated Heparin Bridged to Warfarin

If DOACs are contraindicated or unavailable:

• Initiate unfractionated heparin: 80 units/kg IV bolus, followed by 18 units/kg/hour continuous infusion 1, 3, 4
• Target aPTT: 1.5-2.5 times baseline (corresponding to anti-Xa activity of 0.3-0.6 IU/mL) 1
• Overlap with warfarin for at least 5 days and until INR is therapeutic (2.0-3.0, target 2.5) for 2 consecutive days 1, 5
• Continue heparin for 7-10 days before transitioning fully to warfarin 4, 6

Contraindications to DOACs in This Case

Verify the following before prescribing a DOAC:

• Calculate creatinine clearance (CrCl) - DOACs should not be used if CrCl <15 mL/min for rivaroxaban or <25 mL/min for apixaban 1, 2
• Rule out antiphospholipid antibody syndrome, which requires warfarin therapy 1
• Confirm no active malignancy, particularly gastrointestinal cancer (where LMWH may be preferred) 1

Why Thrombolysis is NOT Indicated

Systemic thrombolysis should NOT be administered to this intermediate-risk patient because:

• The patient is hemodynamically stable without sustained hypotension or cardiogenic shock 1
• Thrombolysis is reserved for high-risk PE with cardiogenic shock and/or persistent arterial hypotension (systolic BP <90 mmHg for ≥15 minutes) 1
• The mortality benefit of thrombolysis does not outweigh bleeding risks in intermediate-risk PE 1
• Current guidelines explicitly state: "Do not routinely administer systemic thrombolysis as primary treatment in patients with intermediate- or low-risk PE" 1

Duration of Anticoagulation

Minimum 3 months of therapeutic anticoagulation is required for all patients with PE. 1, 5

The decision to extend beyond 3 months depends on:

• If provoked by a major transient/reversible risk factor (major surgery, trauma, prolonged immobilization): discontinue after 3 months 1, 5
• If unprovoked or associated with persistent risk factors: consider extended (indefinite) anticoagulation, particularly given the patient's hypertension and age 1, 5
• Reassess bleeding risk and drug tolerance at regular intervals if extended therapy is chosen 1

Monitoring and Follow-up

• If using unfractionated heparin: Check aPTT at 4-6 hours after initiation and 6 hours after each dose adjustment 1
• If using warfarin: Monitor INR frequently during initiation, then at least monthly once stable 5
• Routine clinical evaluation at 3-6 months post-PE to assess for persistent symptoms, functional limitation, or signs of chronic thromboembolic pulmonary hypertension 1

Critical Pitfalls to Avoid

• Do not delay anticoagulation while awaiting additional testing - treatment should begin immediately upon diagnosis confirmation 1, 3
• Do not use inferior vena cava filters routinely - they are reserved for patients with absolute contraindications to anticoagulation or recurrent PE despite adequate anticoagulation 1
• Do not use low-molecular-weight heparin if severe renal impairment is present (CrCl <30 mL/min) due to bioaccumulation risk 1
• Do not administer thrombolysis to intermediate-risk patients outside of clinical deterioration - the bleeding risk outweighs benefit 1