Pulmonary Embolism Due to Thrombosis: An Overview

Pulmonary Embolism Due to Thrombosis: An Overview

Pulmonary embolism (PE) is the third leading cause of acute cardiovascular death, after myocardial infarction and stroke.

Pathogenesis of PE:

• Virchow’s triad: The pathogenesis of PE is described by Virchow’s triad, which includes 3 factors:

• Hypercoagulability

• Venous stasis

• Endothelial damage

• Protective mechanisms: The body has protective mechanisms against thrombus formation, including:

• Non-thrombogenicity of the endothelium

• Natural anticoagulant pathways

• Fibrinolytic system for fibrin degradation

• Thrombogenic factors:

• Activation of coagulation

• Endothelial damage

• Venous stasis

Source of Thrombi:

• Thrombi usually originate from the deep veins of the lower extremities, travel up to the inferior vena cava, reach the right heart, and eventually obstruct the pulmonary arteries.

• Thrombi are often distributed more in the base of the lungs, causing pulmonary artery obstruction, leading to a mismatch between ventilation and perfusion.

• PE causes hypoxemia, hyperventilation, hypocapnia, pulmonary edema, and atelectasis.

• Only about 10% of PE cases cause pulmonary infarction because the lungs are nourished by the bronchial arteries, the pulmonary arteries only play a functional role.

Risk Factors for Pulmonary Embolism:

• The risk of PE is classified into 3 levels:

• High risk: OR > 10

• Moderate risk: OR 2-10

• Low risk: OR < 2

• High Risk:

• Lower extremity fracture

• Hip or knee replacement surgery

• Major trauma

• Spinal cord injury

• Hospitalization for heart failure or atrial fibrillation within the previous 3 months

• Myocardial infarction within the previous 3 months

• Previous VTE

• Moderate Risk:

• Arthroscopic knee surgery

• Hemiplegia

• Pregnancy/postpartum

• Oral contraceptives/Hormone replacement therapy

• Chemotherapy

• Central venous catheter

• Malignancy

• Respiratory failure, chronic heart failure

• Thrombocytosis

• Low Risk:

• Immobilization > 3 days

• Prolonged sitting

• Abdominal surgery

• Obesity

• Varicose veins

• Pregnancy or pre-pregnancy

Clinical Presentation:

• The clinical manifestations of PE vary depending on the degree of obstruction and pre-existing cardiopulmonary disease.

• Common symptoms: Dyspnea and tachycardia.

• Symptoms in massive PE: Dyspnea, syncope, hypotension, cyanosis.

• Symptoms in small, peripheral PE: Cough, pleuritic chest pain, hemoptysis.

Investigations:

• D-Dimer < 500 ng/ml helps exclude PE in about 90%.

• D-Dimer is also elevated in other conditions such as myocardial infarction, pneumonia, sepsis, cancer, post-surgery, and pregnancy.

• Routine laboratory tests are often non-specific.

• Routine tests include:

• Complete blood count

• Erythrocyte sedimentation rate

• LDH, SGOT

• BNP, Troponin

• Arterial blood gas

• Electrocardiogram and chest X-ray

• White blood cell count and erythrocyte sedimentation rate are often elevated in PE.

• LDH and SGOT are usually elevated, SGOT elevation is not accompanied by bilirubin elevation.

• BNP and troponin elevation helps predict the prognosis, indicating anemia or left ventricular damage.

• Arterial blood gas shows hypoxemia, increased alveolar-arterial oxygen gradient, decreased CO2.

• Chest X-ray is normal in PE in about 20%.

• ECG findings in PE:

• Sinus tachycardia

• New right ventricular strain suggestive of diagnosis

• New right bundle branch block

• New S1Q3T3

• PE with normal ECG accounts for about 40%.

• Chest X-ray is not used to diagnose or exclude PE.

• Suspect PE when chest X-ray is normal, dyspnea, tachycardia, hypoxemia.

• X-ray signs in PE:

• Westermark’s sign: Sign of central obstruction, sensitivity 8%

• Hampton’s hump: Triangular or arched opacity, sensitivity 10%

• Westermark’s sign is described as the phenomenon of lung hypoperfusion after artery obstruction, making the obstructed lung appear brighter.

• Hampton’s hump is a triangular or arched opacity, with its base located at the pleura, the apex pointing towards the hilum of the lung, due to secondary pulmonary infarction after pulmonary embolism.

• Normal ECG and X-ray do not exclude pulmonary embolism.

• Abnormal findings on ECG and X-ray are only suggestive of pulmonary embolism.

• S1Q3T3 has a specificity of 97.7% and a sensitivity of 8.5%.

Definitive Diagnosis:

• The gold standard for diagnosing pulmonary embolism is finding a thrombus in the autopsy or pulmonary angiography showing a filling defect.

• PE scoring scales:

• GENEVA score: Primitive and simple, suitable for outpatient settings.

• Wells score: Can be used for both inpatients and outpatients.

• Primitive: > 5 points high risk.

• Simplified: > 2 points high risk.

Diagnostic Approach:

• Hemodynamic assessment:

• If the patient is in shock, hypotensive, high risk of mortality, CT scan immediately.

• If the patient is not in shock, hypotensive, low risk of mortality, assess the probability of PE according to the Wells score.

• If the probability of PE is high, CT scan.

• If the probability of PE is low, D-Dimer quantification.

• If D-Dimer is positive, CT scan.

• If D-Dimer is negative, rule out PE.

• If PE is suspected and there is shock, hypotension: Belonging to the high mortality risk group.

• High risk of mortality:

• Cardiac arrest requiring resuscitation

• Obstructive shock or prolonged hypotension

• Obstructive shock: Systolic blood pressure < 90 mmHg or systolic blood pressure drop > 90 mmHg (vasoconstriction) despite fluid resuscitation, accompanied by tissue hypoperfusion (altered consciousness, oliguria, anuria, cold extremities, elevated Lactate).

• Prolonged hypotension: Systolic blood pressure < 90 mmHg or decrease > 40 mmHg for at least 1 minute without arrhythmia, hypovolemia, or infection.

D-Dimer:

• It is a degradation product of fibrin, not specific for PE, but highly sensitive.

• Value of D-Dimer:

• If D-Dimer is negative, the clinical probability of PE is low, helping to rule out the diagnosis.

• D-Dimer is only meaningful when the clinical probability of PE is low (Wells full < 5, Wells simplified < 2).

• If age > 50, the cut-off of D-Dimer is age x 10 ug.

• If the probability of PE is high (Wells full > 5, Wells simplified > 2), a negative D-Dimer does not rule out PE.

CT Scan:

• Helps visualize thrombi in the pulmonary arteries, with high sensitivity and specificity.

• If CT is negative, but clinically incompatible (high clinical probability), other tests need to be performed for diagnosis.

• Image of thrombus in the lumen:

• Contrast agent surrounding the filling defect

• Contrast agent surrounding the filling defect forming a sharp angle

• Complete occlusion of a pulmonary artery branch

• Filling defect in the shape of pulmonary artery reconstitution

• Only accept images of thrombus in the right or left main pulmonary artery, lobe or segment.

Alternative to CT:

• Ventilation-perfusion scan:

• Does not see thrombi

• Effective in patients with normal chest X-ray

• Lower radiation dose than CT

• Can be used in patients who cannot receive contrast agents

• Results of ventilation-perfusion scan:

• Normal: Rule out diagnosis.

• High probability of PE: Definitive diagnosis.

• Moderate and low probability of PE: Not helpful in diagnosis, neither can it be ruled out.

• Lower extremity venous ultrasound:

• Patients suspected of PE, ultrasound shows thrombus in the proximal deep veins of the lower extremities (from the popliteal vein upwards): Accept PE, treat immediately.

• Thrombus in the distal deep veins of the lower extremities: Further tests are needed for diagnosis.

• The incidence of PE with deep vein thrombosis is about 50%.

• Negative ultrasound: Does not rule out PE.

• Echocardiogram:

• If the patient is suspected of PE, there are hemodynamic abnormalities:

• Echocardiogram to see if there is right ventricular overload.

• If there is no right ventricular overload: Look for other causes.

• If there is right ventricular overload: Stabilize the patient, CT scan to confirm thrombus.

• Value of echocardiogram:

• Helps rule out PE as the cause of shock in patients with hemodynamic abnormalities.

• Definitive diagnosis: Thrombus in the pulmonary artery/heart chambers.

• Echocardiogram only diagnoses when:

• RLCN right ventricle + increased pressure + patient with hemostatic abnormalities + high probability of PE + CT scan cannot be performed + no other cause of hemodynamic abnormalities found.

Consider PE when:

• Sudden onset respiratory symptoms (dyspnea, tachypnea, chest pain, hemoptysis, wheezing).

• Circulatory symptoms (tachycardia, hypotension, shock).

• Risk factors.

Paraclinical Tests:

• ECG, X-ray, blood gas help to decide whether to perform further diagnostics or not 3 points of Wells for criteria (other diagnosis is less likely than PE).

Other Emboli:

• Air embolism

• Tumor embolism

• Fat embolism

• Amniotic fluid embolism

• These emboli are not treated specifically, only thrombosis is treated specifically.

• Air embolism: Occurs acutely after intravenous catheterization, patient coughs a lot, cyanotic, hypotensive, may be completely normal beforehand.

• Tumor embolism: Silent clinical picture, accidentally found pulmonary artery occlusion, cancer cells/in cancer patients.

• Fat embolism: Occurs in patients with multiple trauma.

• Amniotic fluid embolism: Amniotic cells are found in the pulmonary artery, in perinatal patients.

Assessing PE Severity:

• Hemodynamic instability: High risk

• No hemodynamic disturbance: Evaluate according to scoring systems, evaluate right ventricular function by imaging, cardiac biomarkers.

• PE with hemodynamic disturbance: High risk

• PESI score > 4

• Right ventricular dysfunction (+)

• Cardiac biomarkers (+)

• Moderate risk:

• Risk factors: Refer to the list of risk factors in the “Risk Factors for Pulmonary Embolism” section.

Conclusion:

Pulmonary embolism is a dangerous condition, requiring timely diagnosis and treatment. Assessing risk, using appropriate paraclinical tests, and choosing the appropriate diagnostic method are crucial for making optimal treatment decisions for patients.