What is the recommended initial diagnostic work‑up and treatment for an adult patient with suspected pulmonary embolism, including anticoagulation strategy, imaging choice, and therapy duration?

Pulmonary Embolism: Diagnostic Work-up and Treatment

Immediate Anticoagulation

Initiate therapeutic anticoagulation immediately upon suspecting PE with intermediate or high clinical probability—do not wait for imaging confirmation, as delaying anticoagulation significantly increases mortality. 1, 2

• Start unfractionated heparin (UFH) with weight-adjusted bolus of 80 units/kg IV, followed by continuous infusion of 18 units/kg/hour, targeting aPTT 1.5-2.5 times control (45-75 seconds). 1, 2
• For most non-high-risk PE patients, low-molecular-weight heparin (LMWH) or fondaparinux is preferred over UFH due to equal efficacy and improved safety. 1
• Reserve UFH for high-risk (hemodynamically unstable) PE and patients with severe renal impairment (CrCl <30 mL/min), as LMWH accumulates dangerously in renal dysfunction. 1, 3

Diagnostic Algorithm

Step 1: Clinical Probability Assessment

• Use a validated prediction rule (Wells Score or Revised Geneva Score) or structured clinical gestalt before any testing—this is mandatory and must be documented. 1, 2
• Key clinical features: respiratory rate >20/min, tachypnea, dyspnea, hypoxemia, recent immobilization/surgery, lower limb trauma, clinical DVT, previous VTE, pregnancy, or major medical illness. 1, 2
• Common pitfall: PE is frequently missed in elderly patients with severe pre-existing cardiorespiratory disease, especially when isolated dyspnea is the only symptom. 1, 2, 3

Step 2: D-dimer Testing (Selective Use Only)

• Order D-dimer only in patients with low or intermediate clinical probability—never in high-probability patients, as a normal result does not safely exclude PE even with highly sensitive assays. 1, 2
• A negative high-sensitivity D-dimer (<500 ng/mL) reliably excludes PE in low and intermediate probability patients without further testing. 1, 2
• Consider age-adjusted D-dimer cutoff (age × 10 ng/mL in patients >50 years) to reduce unnecessary imaging while maintaining safety. 1

Step 3: Imaging

• CT pulmonary angiography (CTPA) is the first-line imaging modality for suspected PE. 1, 2
• A normal CTPA in low or intermediate probability patients excludes PE without further testing. 1
• CTPA showing segmental or more proximal filling defects in intermediate or high probability patients confirms PE. 1
• Critical caveat: Isolated subsegmental defects may represent false-positives—discuss with radiology and consider seeking a second opinion before committing to potentially harmful long-term anticoagulation. 1, 2
• For hemodynamically unstable patients, perform bedside echocardiography immediately to differentiate high-risk PE from other acute life-threatening conditions (acute MI, tamponade, aortic dissection). 1
• Compression ultrasound (CUS) of lower extremities showing proximal DVT is sufficient to warrant anticoagulation without further PE imaging, though risk stratification for PE severity is still required. 1

Risk Stratification After PE Confirmation

High-Risk PE (Hemodynamically Unstable)

• Defined by systemic hypotension (SBP <90 mmHg or drop ≥40 mmHg for >15 minutes) or cardiogenic shock. 1
• Systemic thrombolytic therapy is first-line treatment for high-risk PE, significantly reducing mortality (OR 0.53, NNT 59). 1, 4
• Surgical pulmonary embolectomy is recommended when thrombolysis is contraindicated or has failed. 1
• Percutaneous catheter-directed treatment should be considered as alternative to surgery when thrombolysis fails or is contraindicated. 1
• Consider norepinephrine and/or dobutamine for hemodynamic support. 1

Intermediate-Risk PE (Hemodynamically Stable with RV Dysfunction)

• Continue therapeutic anticoagulation and monitor closely for clinical deterioration. 1, 2
• Routine primary thrombolysis is not recommended—reserve as rescue therapy only if hemodynamic deterioration occurs despite anticoagulation. 1

Low-Risk PE

• Consider early discharge (within 24-48 hours) and home treatment continuation if proper outpatient care can be provided. 1

Anticoagulation Management

Initial Phase

• When starting oral anticoagulation, prefer a direct oral anticoagulant (DOAC)—apixaban, rivaroxaban, dabigatran, or edoxaban—over the traditional LMWH-VKA regimen. 1
• DOACs have fewer hemorrhagic complications than vitamin K antagonists without increased recurrence risk (HR 0.84-1.09). 4, 5
• Absolute contraindications to DOACs: severe renal impairment (CrCl <30 mL/min for most DOACs), pregnancy, lactation, and antiphospholipid antibody syndrome. 1

Parenteral-to-Oral Transition (if using VKA)

• Heparin must continue for minimum 5 days regardless of how quickly INR becomes therapeutic—shorter durations increase recurrence rates. 1, 6
• Discontinue heparin only after 5 days AND INR ≥2.0 for at least 2 consecutive days, targeting INR 2.0-3.0. 1, 6
• Monitor aPTT: 4-6 hours after initial bolus, 6-10 hours after dose changes, then daily once therapeutic. 1, 6

Duration of Anticoagulation

• Provoked PE (temporary risk factors): 3 months minimum. 2, 5
• Unprovoked/idiopathic first episode: 3-6 months, then reassess for extended therapy based on bleeding risk versus recurrence risk. 2, 5
• Recurrent PE or active cancer: Consider indefinite anticoagulation given heightened recurrence risk and overall DOAC safety. 2, 5
• For cancer patients, DOACs (rivaroxaban, apixaban, edoxaban) are equally effective alternatives to LMWH. 2

Special Populations

Elderly with Renal Impairment

• Use UFH rather than LMWH due to predictable clearance independent of renal function. 3
• Careful bleeding risk monitoring is essential, as both advanced age and renal impairment compound hemorrhage risk. 3

Inferior Vena Cava Filters

• Consider IVC filters only in patients with acute PE and absolute contraindications to anticoagulation, or recurrent PE despite therapeutic anticoagulation. 1
• Routine use of IVC filters is not recommended. 1

Critical Pitfalls to Avoid

• Delaying anticoagulation while awaiting diagnostic confirmation—this significantly increases mortality. 2, 7, 8
• Using LMWH in severe renal dysfunction (CrCl <30 mL/min). 1, 3
• Ordering D-dimer in high-probability patients. 1
• Discontinuing heparin before 5 days even if INR is therapeutic. 6
• Missing PE diagnosis in elderly patients with atypical presentations (isolated dyspnea). 1, 2, 3
• Treating isolated subsegmental defects without radiologist confirmation to avoid unnecessary anticoagulation. 1, 2