1. Dr. M. A. Sofi MD; FRCP; FRCPEdin; FRCSEdin

2.  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

3.  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)

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

6. 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 Cardiovascular:  Congenital heart disease.  Congestive cardiac failure.  Hypertension.  Paralytic stroke. Oestrogens:  Pregnancy  Combined oral contraceptive.  Hormone replacement therapy. Renal:  Nephrotic syndrome.  Chronic dialysis.  Paroxysmal nocturnal haemoglobinuria Risk Factors:

7. Malignancy:  Abdominal/pelvic.  Advanced/metastatic. Reduced mobility:  Hospitalization.  Institutional care. Previous proven VTE:  Intravenous (IV) drug use Other:  Major trauma.  Spinal cord injury.  Central venous lines. 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. Risk Factors:

8. 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:

9. 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%  S 3 or S 4 gallop: 34%  Clinical signs and symptoms suggesting thrombophlebitis: 32%  Lower extremity edema: 24%  Cardiac murmur: 23%  Cyanosis: 19% Presentation:

10. Diagnostic testing I required on symptomatic patients to 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 include:  D-dimer testing  Ischemia-modified albumin level  White blood cell count  Arterial blood gases:  Serum troponin levels  Brain natriuretic peptide Testing:

11. Imaging studies that aid in the diagnosis of P/E include:  Chest radiography: Abnormal in most cases of pulmonary embolism, but nonspecific  Computed tomography angiography (CTA): is the standard for diagnosing P/E  Duplex ultrasonography: Noninvasive diagnosis of pulmonary embolism by demonstrating the presence of a DVT at any site  Pulmonary angiography: Criterion standard for diagnosing pulmonary embolism when CTA is not available  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: Pulmonary emboli demonstrate increased signal intensity within the PA  Echocardiography: Transesophageal echocardiography may identify central pulmonary embolism Imaging:

12. Chest Radiography  Usually nonspesific  Not sensitive or specific  Proximal, large segmental artery  Multiple small segmental artery  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

13. S1 Q3 T3 and T WAVE CHANGES

14.  If PE is suspected, use the two-level PE Wells' score to estimate the clinical probability of PE  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. Assessment: Treatment may precede investigations if the patient is very ill

15.  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. Assessment: Treatment may precede investigations if the patient is very ill

16. 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. 3.0 Tachycardia (heart rate above 100 beats per minute). 1.5 Immobilization for more than three days or surgery in the previous four weeks 1.5 History of DVT or PE. 1.5 Haemoptysis. 1.0 Malignancy (on treatment in the preceding six months or palliative stage). 1.0 Clinical probability 4 points or less = PE unlikely. More than 4 points = PE likely.

17. 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 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.

18. Deep Vein Thrombosis

19. PERFUSION/VENTILATION LUNG SCAN

21. Anticoagulation medications include the following:  Unfractionated heparin  Low-molecular-weight heparin  Factor Xa Inhibitors  Warfarin Thrombolytic agents used in include:  Alteplase  Reteplase  Urokinase  Streptokinase Surgical options  Surgical options include:  Catheter embolectomy and fragmentation  Surgical embolectomy  Placement of vena cava filters Management:

22. Anticoagulation:  Immediate anticoagulation is mandatory for all suspected of having DVT or P/E.  Diagnostic investigations should not delay empirical anticoagulant therapy. Thrombolytic therapy i. should be used in patients who have hypotension (SBP< 90 mm Hg) ii. who do not have a high bleeding risk. iii. In selected patients with acute P/E 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. Management:

23. 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

24. 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) TREATMENT

25. An alternative in high-risk PE patients when thrombolysis is absolutely contraindicated or has failed

26. Prognosis  Mortality rate – 30%  Depends on associated pathology  Resolution – 5 days 36% 2 weeks 52% 3 months 73% Pulmonary hypertension recurrent microemboli (rare) TREATMENT