What is the recommended diagnostic work‑up and treatment for a patient presenting with acute dyspnea, pleuritic chest pain, tachypnea, tachycardia, hypoxia or unexplained syncope and risk factors such as recent surgery, immobilisation, active cancer, prior venous thromboembolism, hormonal therapy, obesity or inherited thrombophilia?

Diagnostic Work-Up and Treatment for Suspected Acute Pulmonary Embolism

Start therapeutic anticoagulation with unfractionated heparin (80 U/kg IV bolus) immediately based on the clinical presentation described—acute dyspnea, pleuritic chest pain, tachypnea, tachycardia, hypoxia, and multiple VTE risk factors—while simultaneously arranging CT pulmonary angiography within 1 hour. 1

Immediate Actions Upon Presentation

Hemodynamic Assessment (First Priority)

• Measure blood pressure immediately to identify high-risk PE: systolic BP <90 mmHg or a ≥40 mmHg drop lasting >15 minutes defines hemodynamic instability and mandates emergent reperfusion therapy. 1
• If the patient is hypotensive or in shock, perform bedside transthoracic echocardiography immediately to assess right ventricular dysfunction and acute pulmonary hypertension. 1
• In critically unstable patients with echocardiographic evidence of RV overload, initiate systemic thrombolysis immediately without awaiting CT confirmation. 1

Vital Signs Documentation

• Record respiratory rate in all cases; tachypnea >20/min is present in >90% of PE cases and its absence virtually excludes PE. 2, 1, 3
• Document heart rate; tachycardia ≥95 bpm significantly increases clinical probability. 3
• Measure oxygen saturation but never use normal SaO₂ to exclude PE—up to 40% of PE patients have normal oxygen saturation. 3

Immediate Anticoagulation (Do Not Delay)

The single most critical step is starting therapeutic anticoagulation before any imaging confirmation. 1, 3

• Administer unfractionated heparin 80 U/kg IV bolus immediately, followed by 18 U/kg/hour infusion. 2, 1
• Delaying anticoagulation while awaiting imaging significantly increases the risk of subsequent VTE events and 3-month sudden cardiac death. 1
• This recommendation applies to all patients with high or intermediate clinical suspicion, even before diagnostic confirmation. 2, 3, 4

Diagnostic Work-Up Algorithm

Step 1: Clinical Probability Assessment

Do not order D-dimer testing in this patient—the combination of acute dyspnea, pleuritic chest pain, tachypnea, tachycardia, hypoxia, and multiple VTE risk factors (recent surgery, immobilization, active cancer, prior VTE, hormonal therapy, obesity, inherited thrombophilia) establishes high clinical probability. 1, 3

• Risk factors are present in 80-90% of PE patients, with the most common being immobilization >1 week, prior VTE, recent surgery, and lower limb fractures. 2, 3
• D-dimer testing is contraindicated in high-probability patients because a negative result does not reliably exclude PE. 1, 3

Step 2: Initial Diagnostic Tests (Perform Simultaneously)

Obtain chest radiography, ECG, and arterial blood gas analysis in all suspected PE cases. 2, 3

• Chest X-ray: Abnormal in >80% of PE cases (though findings are non-specific); helps exclude alternative diagnoses such as pneumothorax or pneumonia. 3, 5
• ECG: May reveal right ventricular strain patterns (T-wave inversion V1-V4, S1Q3T3, right bundle branch block) with 97.4% specificity for PE. 1, 5
• Arterial blood gas: Frequently demonstrates hypoxia and hypocapnia, though approximately 20-25% of PE patients have normal PaO₂. 2, 5

Step 3: Definitive Imaging

For hemodynamically stable patients, CT pulmonary angiography (CTPA) is the first-line diagnostic test and should be performed within 1 hour of suspicion. 1, 3

• A positive CTPA demonstrating segmental or more proximal filling defects confirms the diagnosis. 1, 3, 4
• A high-quality negative CTPA in high-probability patients excludes PE; no additional testing is required. 3

Alternative imaging pathways when CTPA is contraindicated:

• Ventilation-perfusion (V/Q) scan may be used when CTPA is unavailable or contraindicated (renal failure, contrast allergy, pregnancy), but only if the chest X-ray is normal and the patient has no significant chronic cardiopulmonary disease. 2, 3
• A normal perfusion scan effectively excludes PE. 3
• A high-probability V/Q scan in the context of high clinical probability confirms PE. 2, 3
• All other V/Q result/clinical-probability combinations require CTPA or pulmonary angiography for definitive diagnosis. 3

Step 4: Lower-Extremity Venous Ultrasound (Selective Use)

Perform compression ultrasound as a first-line investigation in patients with clinical signs of DVT, prior PE, or chronic cardiorespiratory disease. 2, 3

• Detection of proximal DVT confirms venous thromboembolism and justifies anticoagulation without pulmonary imaging. 1, 3
• A normal lower-extremity ultrasound does not exclude PE—only 30-50% of PE patients have detectable DVT; proceed to lung imaging if ultrasound is negative. 3

Treatment Based on Risk Stratification

High-Risk PE (Hemodynamically Unstable)

Immediate systemic thrombolysis is indicated in patients with shock or persistent hypotension. 2

Thrombolytic regimens (stop heparin before administration): 2

• rtPA: 100 mg IV over 2 hours
• Streptokinase: 250,000 units IV over 20 minutes, then 100,000 units/hour for 24 hours (plus hydrocortisone to prevent circulatory instability)
• Urokinase: 4,400 IU/kg IV over 10 minutes, then 4,400 IU/kg/hour for 12 hours

Thrombolysis reduces mortality by 1.6% absolute risk reduction (from 3.9% to 2.3%) in hypotensive patients. 6

Intermediate-Risk PE (Hemodynamically Stable with RV Dysfunction)

Close monitoring in a monitored setting; consider escalation if deterioration occurs. 1

• RV dysfunction on echocardiography or CT, or elevated cardiac biomarkers (troponin/BNP) define intermediate risk. 1

Low-Risk PE (Hemodynamically Stable, No RV Dysfunction)

Standard anticoagulation alone is sufficient. 1

Anticoagulation Management

Initial Heparin Therapy

Unfractionated heparin dosing: 2

• Initial bolus: 80 U/kg IV (or 5,000-10,000 IU standard dose)
• Maintenance infusion: 18 U/kg/hour (or 1,300 IU/hour standard dose)
• Target APTT: 1.5-2.5 × control (45-75 seconds)

APTT monitoring schedule: 2

• After initial bolus: 4-6 hours later
• After any dose change: 6-10 hours later
• Once therapeutic: Daily

Transition to Oral Anticoagulation

Continue heparin for at least 5 days and until INR ≥2.0 for 24 hours. 2

Warfarin dosing: 2

• Initial: 5-10 mg daily for 2 days
• Maintenance: 1-10 mg daily, adjusted to INR 2.0-3.0

Direct oral anticoagulants (DOACs) are preferred over warfarin in hemodynamically stable patients—apixaban, edoxaban, rivaroxaban, or dabigatran are noninferior for treating PE and have a 0.6% lower rate of bleeding compared to warfarin. 6

Duration of Anticoagulation

For first episode with temporary risk factors: Anticoagulation may be discontinued after 3-6 months. 2

For idiopathic or recurrent PE: Consider extended anticoagulation and investigate for thrombophilic disorders or occult malignancy. 2

Critical Pitfalls to Avoid

• Never postpone therapeutic anticoagulation while awaiting imaging in high-probability patients—this is the most common and dangerous error. 1
• Never rely on normal oxygen saturation to rule out PE; up to 40% of patients may have normal SaO₂. 1, 3
• Never order D-dimer in high-probability patients or hospitalized patients with comorbidities (infection, cancer, inflammation, recent surgery)—false-positive rates exceed 10%. 3
• Never perform V/Q scanning if the chest X-ray is abnormal or if chronic cardiopulmonary disease is present—results are likely nondiagnostic. 3
• Never delay imaging beyond 24 hours in non-massive PE or beyond 1 hour in suspected massive PE. 3