What is the recommended anticoagulation therapy for patients with pulmonary embolism?

Anticoagulation for Pulmonary Embolism

For patients with acute pulmonary embolism, initiate anticoagulation immediately with either low-molecular-weight heparin (LMWH) or fondaparinux, then transition to a direct oral anticoagulant (DOAC) such as rivaroxaban or apixaban, which are preferred over warfarin for long-term therapy. 1, 2

Initial Anticoagulation Strategy

Hemodynamically Stable Patients (Intermediate or Low-Risk PE)

• Prefer LMWH or fondaparinux over unfractionated heparin (UFH) for initial parenteral anticoagulation in patients without hemodynamic instability 1
• Initiate anticoagulation immediately in patients with high or intermediate clinical probability while diagnostic workup is in progress—do not delay treatment awaiting confirmation 1, 2

Hemodynamically Unstable Patients (High-Risk PE)

• Administer UFH intravenously without delay using a weight-adjusted bolus of 80 U/kg followed by continuous infusion at 18 U/kg/h 1, 2, 3
• Adjust subsequent UFH doses based on activated partial thromboplastin time (aPTT) to maintain 1.5-2.5 times control value 2, 3
• Administer systemic thrombolytic therapy to patients with high-risk PE presenting with cardiogenic shock or persistent arterial hypotension 1, 4
• Do not routinely administer systemic thrombolysis in patients with intermediate- or low-risk PE 1, 4

Transition to Oral Anticoagulation

DOAC Therapy (Preferred)

• When initiating oral anticoagulation, prefer a DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) over vitamin K antagonists in eligible patients 1, 2
• Rivaroxaban dosing: 15 mg orally twice daily for 3 weeks, then 20 mg once daily 2
• Apixaban is an effective alternative, particularly in cancer patients, with higher dosing during the first week followed by maintenance dosing 2
• Dabigatran requires at least 5-10 days of parenteral anticoagulation before initiation 2

Vitamin K Antagonist (VKA) Therapy (Alternative)

• As an alternative to DOACs, administer a VKA overlapping with parenteral anticoagulation until an INR of 2.5 (range 2.0-3.0) has been reached for 2 consecutive days 1, 5
• Target INR of 2.5 (range 2.0-3.0) for all treatment durations 5

Duration of Anticoagulation

• Administer therapeutic anticoagulation for at least 3 months to all patients with PE 1
• Discontinue anticoagulation after 3 months in patients with first PE secondary to a major transient/reversible risk factor 1, 5
• Continue oral anticoagulation indefinitely in patients with recurrent VTE (at least one previous episode of PE or DVT) not related to a major transient or reversible risk factor 1
• For patients with first episode of idiopathic PE, continue anticoagulation for at least 6-12 months 5
• Reassess drug tolerance, adherence, hepatic and renal function, and bleeding risk at regular intervals in patients receiving extended anticoagulation 1

Special Populations

Cancer Patients

• LMWH is the preferred initial and long-term treatment for cancer patients with PE 2
• Dalteparin dosing: 200 IU/kg once daily for 1 month, then 150 IU/kg once daily for 5 months 2
• Apixaban is an effective alternative in cancer patients 2

Pregnancy

• Administer therapeutic, fixed doses of LMWH based on early pregnancy weight in pregnant women without hemodynamic instability 1
• Do not use DOACs during pregnancy or lactation 1

Renal Impairment

• Do not use DOACs in patients with severe renal impairment (CrCl <30 mL/min) 1
• UFH is preferred in severe renal dysfunction 2

Antiphospholipid Antibody Syndrome

• Continue oral anticoagulant treatment with a VKA indefinitely in patients with antiphospholipid antibody syndrome—do not use DOACs in this population 1

Critical Pitfalls to Avoid

• Never delay anticoagulation while awaiting diagnostic confirmation in patients with high or intermediate clinical probability 2
• Do not stop parenteral anticoagulation before achieving therapeutic INR for 2 consecutive days when using VKAs 2
• Avoid aggressive fluid resuscitation in high-risk PE, as it can worsen right ventricular failure 2
• Do not routinely use inferior vena cava filters 1

Alternative Interventions for High-Risk PE

• Surgical pulmonary embolectomy is recommended for patients with high-risk PE in whom thrombolysis is contraindicated or has failed 1, 4
• Percutaneous catheter-directed treatment should be considered for high-risk PE patients with contraindications to thrombolysis or in whom thrombolysis has failed 4
• For complex cases, especially intermediate-high risk PE, involvement of a Pulmonary Embolism Response Team (PERT) is encouraged 4