Dr. M. A. Sofi MD; FRCP; FRCPEdin; FRCSEdin PULMONARY EMBOLISM Dr. M. A. Sofi MD; FRCP; FRCPEdin; FRCSEdin

Pulmonary Embolism PE is the most common preventable cause of death in hospitalized patients 600,000 deaths/year 80% of pulmonary emboli occur without prior warning signs or symptoms 2/3 of deaths due to pulmonary emboli occur within 30 minutes of embolization Death due to massive PE is often immediate Diagnosis can be difficult Early treatment is highly effective

Natural History of VTE 40-50% of pts with DVT develop PE, often “silent” PE presents 3-7 days after DVT Fatal within 1 hour after onset of respiratory symptoms in 10% Shock/persistent hypotension in 5-10% (up to 50% of patients with RV dysfunction) Most fatalities occur in untreated pts Perfusion defects completely resolve in 75% of all patients (who survive)

RISK FACTORS Acquired Risk factors (III) Inherited Risk Factors (2) Antithrombin III deficiency Protein C deficiency Protein S deficiency Protein C resistance (Factor V Leiden) Hyperhomocystinemia Abnormal fibrinogen Abnormal fibrinolytic system Inherited Risk Factors Family History (+) Acquired risk factor (+) Prior deep venous thrombosis Acquired Risk factors (III) Prior DVT Nephrotic Syndrome Antiphospholipid Syndrome PNH Waldenström Macroglobinemia

Risk Factors: Major risk factors: relative risk of 5-20 Surgery: Major abdominal/pelvic surgery or hip/knee replacement (risk lower if prophylaxis used). Postoperative intensive care. Obstetrics: Late pregnancy. Puerperium. Caesarean section Lower limb problems: Fracture. Varicose veins - previous varicose vein surgery; superficial thrombophlebitis; varicose veins per se are not a risk factor Minor risk factors: relative risk of 2-4 Cardiovascular: Congenital heart disease. Congestive cardiac failure. Hypertension. Paralytic stroke. Oestrogens: Pregnancy (but see major risk factors for late pregnancy and puerperium). Combined oral contraceptive. Hormone replacement therapy. Renal: Nephrotic syndrome. Chronic dialysis. Paroxysmal nocturnal haemoglobinuria

Risk Factors: Major risk factors: relative risk of Malignancy: Abdominal/pelvic. Advanced/metastatic. Reduced mobility: Hospitalization. Institutional care. Previous proven VTE: Intravenous (IV) drug use (could be major or minor risk factor: no data on relative risk). Other: Major trauma. Spinal cord injury. Central venous lines. Minor risk factors: relative risk of Hematological: Thrombotic disorders Consider this in cases of PE aged <40 years, recurrent VTE or a positive family history. Myeloproliferative disorders Miscellaneous: Chronic obstructive pulmonary disease (COPD). Neurological disability. Occult malignancy. Long-distance sedentary travel. Obesity. Other chronic diseases: inflammatory bowel disease, Behçet's disease.

Presentation: The classic presentation of PE is the abrupt onset of pleuritic chest pain. Shortness of breath. Hypoxia. Most patients with PE have no obvious symptoms at presentation. Symptoms may vary from sudden catastrophic hemodynamic collapse to gradually progressive dyspnea. The diagnosis of pulmonary embolism should be suspected in patients with respiratory symptoms unexplained by an alternative diagnosis Patients with PE may present with atypical symptoms, such as the following: Seizures Syncope Abdominal pain Fever Productive cough Wheezing Decreasing level of consciousness New onset of atrial fibrillation Hemoptysis Flank pain Delirium (in elderly patients)

Presentation: Evidence-based literature supports the practice of using clinical scoring systems to determine the clinical probability of pulmonary embolism before proceeding with testing. Validated clinical prediction rules should be used to estimate pretest probability of pulmonary embolism and to interpret test results Physical signs of pulmonary embolism include the following: Tachypnea (respiratory rate >16/min): 96% Rales: 58% Accentuated second heart sound: 53% Tachycardia (heart rate >100/min): 44% Fever (temperature >37.8°C): 43% Diaphoresis: 36% S3 or S4 gallop: 34% Clinical signs and symptoms suggesting thrombophlebitis: 32% Lower extremity edema: 24% Cardiac murmur: 23% Cyanosis: 19%

Testing: Perform diagnostic testing on symptomatic patients with suspected Pet o confirm or exclude the diagnosis or until an alternative diagnosis is found. Routine laboratory findings are nonspecific and are not helpful in pulmonary embolism. A hypercoagulation workup should be performed if no obvious cause for embolic disease is apparent, including screening for conditions such as the following: Antithrombin III deficiency Protein C or Protein S deficiency Lupus anticoagulant Homocystinuria Occult neoplasm Connective tissue disorders Potentially useful laboratory tests in patients with suspected pulmonary embolism include the following: D-dimer testing Ischemia-modified albumin level White blood cell count Arterial blood gases: Serum troponin levels Brain natriuretic peptide

Imaging: Imaging studies that aid in the diagnosis of pulmonary embolism include the following: Computed tomography angiography (CTA): Multidetector- row CTA (MDCTA) is the criterion standard for diagnosing pulmonary embolism Pulmonary angiography: Criterion standard for diagnosing pulmonary embolism when MDCTA is not available Chest radiography: Abnormal in most cases of pulmonary embolism, but nonspecific V/Q scanning: When CT scanning is not available or is contraindicated ECG: Most common abnormalities are tachycardia and nonspecific ST- T wave abnormalities MRI: Using standard or gated spin- echo techniques, pulmonary emboli demonstrate increased signal intensity within the pulmonary artery Echocardiography: Transesophageal echocardiography may identify central pulmonary embolism Venography: Criterion standard for diagnosing DVT Duplex ultrasonography: Noninvasive diagnosis of pulmonary embolism by demonstrating the presence of a DVT at any site

Chest Radiography (II) Laboratory Tests Atelectasis Elevation of the hemidiaphragm Pleural efusion Dilatation of the main branches of PA Paranchymal densities (in the lower lung fields, pleural based) Zones of oligemia Laboratory Tests Chest Radiography Usually nonspesific Not sensitive or specific Proximal, large segmental artery Multiple small segmental artery

S1 Q3 T3 and T WAVE CHANGES

An immediate computed tomography pulmonary angiogram (CTPA) or Assessment NB: treatment may precede investigations if the patient is very ill If PE is suspected, use the two-level PE Wells' score to estimate the clinical probability of PE Offer patients in whom PE is suspected and with a likely two-level PE Wells' score either An immediate computed tomography pulmonary angiogram (CTPA) or Immediate interim parenteral anticoagulant therapy followed by a CTPA, If a CTPA cannot be carried out immediately. Consider a proximal leg vein ultrasound scan if the CTPA is negative and DVT is suspected.

D-dimer test if the result is positive: Assessment NB: treatment may precede investigations if the patient is very ill D-dimer test if the result is positive: Immediate CTPA or immediate interim parenteral anticoagulant therapy followed by a CTPA, if a CTPA cannot be carried out immediately. For patients who have an allergy to contrast media, or who have renal impairment, or whose risk from irradiation is high: Assess the suitability of a ventilation/perfusion single- photon emission computed tomography (V/Q SPECT) If offering a V/Q SPECT or planar scan that will not be available immediately, offer immediate interim parenteral anticoagulant therapy.

Wells' Two-level PE Score Clinical feature Point Clinically suspected DVT (minimum leg swelling and pain on palpation of deep veins). 3.0 Alternative diagnosis less likely than PE. Tachycardia (heart rate above 100 beats per minute). 1.5 Immobilization for more than three days or surgery in the previous four weeks History of DVT or PE. Haemoptysis. 1.0 Malignancy (on treatment in the preceding six months or palliative stage). Clinical probability 4 points or less = PE unlikely. More than 4 points = PE likely.

Echocardiography Laboratory Tests Shows emboli in main pulmonary arteries, but not in lober and segmentaL arteries Dilated hypokinetic RV Distorsion of the interventricular septum in diastole Tricuspid regurgitation associated with increase in systolic pressure in pulmonary artery Laboratory Tests Arterial Blood Gases Acute PaCO2 decreases Massive PaO2 decreases Submassive Normal / Near normal

Ventilation-Perfusion Lung Scan It remains the first line investigation of possible PE. It should be performed in all clinically stable patients. A Ventilation Perfusion scan is most useful when the result category is one of normal , low or high probability. Perfusion (-) and Ventilation (+) PE Perfusion (N) and Clinical sym and signs (N) PE excluded Low probability PVLS and low probability of clinical sym and signs PE excluded High probability PVLS and high probability of clinical symp and signs Anticoagulation

Deep Vein Thrombosis

PERFUSION/VENTILATION LUNG SCAN

PERFUSION/VENTILATION LUNG SCAN

This algorithm allowed for a management decision in 98% of patients presenting with symptoms suggestive of PE

Management: Anticoagulation medications include the following: Unfractionated heparin Low-molecular-weight heparin Factor Xa Inhibitors Fondaparinux Warfarin Thrombolytic agents used in managing pulmonary embolism include the following: Alteplase Reteplase Urokinase Streptokinase Surgical options Surgical management options include the following: Catheter embolectomy and fragmentation or surgical embolectomy Placement of vena cava filters

Management: Anticoagulation and thrombolysis Immediate full anticoagulation is mandatory for all patients suspected of having DVT or pulmonary embolism. Diagnostic investigations should not delay empirical anticoagulant therapy. Thrombolytic therapy should be used in patients with acute pulmonary embolism who have hypotension (systolic blood pressure< 90 mm Hg) who do not have a high bleeding risk. In selected patients with acute pulmonary embolism not associated with hypotension who have a low bleeding risk and whose initial clinical presentation or clinical course suggests a high risk of developing hypotension.

Spiral CT Direct visualization of emboli. Both parenchymal and mediastinal structures can be evaluated. Offers differential diagnosis in 2/3 of cases with a negative scan. BUT… Dye load and large radiation dose Optimally used when incorporated into a validated diagnostic decision tree

Clinical Probability of acute PE High Probability (80-100%) Risk factors (+) Dyspnea Tachypnea Chest pain Radiology (+) PaO2 decreases P (A-a)O2 increases Intermediate Probability (20-79%) Low Probability (1-19%) Risk Factors (-) Clinical and laboratory findings can be explained Treatment To prevent death To reduce morbidity To prevent pulmonary hypertension Progresing due to thromboemboli

TREATMENT Prognosis Mortality rate – 30% Depends on associated pathology Resolution – 5 days 36% 2 weeks 52% 3 months 73% Pulmonary hypertension recurrent microemboli (rare) Anticoagulation Unfractioned heparin LMWH Thrombolysis Embolectomy

TREATMENT long acting less binding to plasma protein Unfractioned Heparin IV 5000 U bolus + 30-35 000 U/kg aPTT- twice the control value Thrombocytopenia Early: thrombocyte aggregation slight, reveresible, no need to stop Late: antibodies against thrombocytes arterial and venous thromboemboli Osteopenia LMWH long acting less binding to plasma protein greater bioavailibity no need monitoring

TREATMENT Thrombolysis Massive pulmonery emboli with hemodynamic instability Streptokinase Urokinase t-PA **serious bleeding Secondary prevention UFH + oral anticoagulan (6 months) LMWH SC + oral anticoagulan (6 months ) LMWH (pregnancy) Recurrance / unknown origin / permanantly increased risk (throughout life)

Catheter Embolectomy & Fragmentation An alternative in high-risk PE patients when thrombolysis is absolutely contraindicated or has failed