By Maisa Mansour, MD Pulmonary medicine JUH Pulmonary Embolism By Maisa Mansour, MD Pulmonary medicine JUH

Definition Blood clot, usually from the deep veins of the leg, also air, fat, tumor, that occludes pulmonary vasculature.

Epidemiology PE is a major cause of death in the United States, with as many as 650,000 cases/yr 50,000 to 200,000 fatalities annually. •>400,000 diagnoses of PE are missed in the United States annually. •Most deaths from PE are due to failure to diagnose rather than failure to treat adequately. •Two thirds of patients die within 1 hour of symptom onset; this is the golden hour.

Epidemiology Mortality is 15% within 3 months after occurrence In 25% of PE, the initial manifestation is death

Risk Factors Virchow’s triad Stasis Venous injury/endothelial damage Hypercoagulability Most patients have several of these…

Risk Factors Inherited Acquired Factor V leiden Prothrombin gene mutation Low protein C, protein S, antithrombin III Family history of VTE Acquired Age Smoking Obesity immobility Malignancy Antiphospholipid antibody syndrome [venous and arterial] Hyperhomocysteinemia [venous and arterial] Oral contraceptive pills or hormone replacement therapy. Atherosclerosis Trauma, surgery, hospitalization Infection Long haul air travel Electronic leads, indwelling catheters

Who gets Evaluated For Thrombophilia? Patients in whom there is a high clinical suspicion for underlying disorder PE not associated with acquired risk factor Family history Initial evaluation directed towards most common Most common Factor V Leiden Prothrombin gene mutation APL Ab syndrome Hyperhomocysteinemia Less common Protein C&S deficiency, ATIII deficiency

Diagnosis pathophysiology is complex and results in variable clinical presentation…

Acute PE: Pathophysiology Gas exchange abnormalities Right to left shunt Leads to… Hypoxemia Increased A–a gradient. V/Q mismatch. Increased dead space Respiratory alkalosis from hyperventilation Often a sign of increased dead space and impaired minute ventilation may suggest massive PE

Acute PE: Pathophysiology Hemodynamic abnormalities Depends on size of embolus Increased vascular resistance/RV afterload May cause RV dilation, then, FAILURE

Diagnosis Symptoms and Signs Dyspnea Chest pain (pleuritic) Apprehension Cough Hemoptysis Syncope Palpitations Wheezing Leg pain Leg swelling Signs Tachycardia Tachypnea hypoxemia Accentuated S2 Fever Diaphoresis Signs of DVT Cardiac murmur Jugular venous distention Cyanosis Hypotension

Diagnosis Laboratory Evaluation D-dimer Non specific measure of fibrinolysis High sensitivity (positive in presence of dz) High negative predictive value (dz is absent when test is negative) in the outpatient setting Useful in outpatient setting/emergency room, not an inpatient test for ruling out PE

Diagnosis Chest XR CXR Most often normal May show collapse, consolidation, small pleural effusion, elevated diaphragm.

Diagnosis V/Q scans Old standard Currently reserved for Renal impairment IV contrast allergies Pregnancy

Diagnosis VQ Scan Perfusion Ventilation Mismatch Intro: Pulmonary Embolus Diagnosis VQ Scan Perfusion Ventilation Mismatch Training Week April 2005 15

Diagnosis CT scan – New Standard Data suggests CT is as accurate as invasive angiography (gold standard) Negative predictive value of 99% Quiroz et al, JAMA 2005

Diagnosis Spiral CT/ Multislice Intro: Pulmonary Embolus Diagnosis Spiral CT/ Multislice Main Pulmonary Artery Ascending Aorta Descending Aorta Rt Pulmonary Artery Lt Pulmonary Artery Thrombus Training Week April 2005 17

Diagnostic algorithm Outpatient/ED Inpatient D-dimer normal Elevated No PE Chest CT 3rd gen scanner Ist gen scanner No PE PE No PE PE Ultrasound of leg veins DVT No DVT PAgram if continued clinical suspicion

ECHO for Risk Stratification Insensitive for diagnosis but can risk stratify in patients with known PE In normotensive patients RV dysfunction is an independent risk factor for early death

Risk stratification algorithm Hemodynamically stable/no shock Unstable/shock BNP BNP (RV on CT) Troponin troponin (RV on CT) ECHO No RV dysfunction RV dysfunction anticoagulation Fibrinolysis, embolectomy

Treatment Anticoagulation Mainstay of therapy Unfractionated heparin . LMWH (low molecular weight heparin). More predictable response No dose adjustments Renally cleared. Some pts need adjustments Kidney dz, pregnancy, massive obesity may need anti factor Xa monitoring Usefulness questioned as correlation with antithrombotic effect not clear

Treatment Warfarin Vitamin K antagonist Dose response variation may be in part attributable to the vitamin K epoxide reductase complex 1 (VKORC1) Testing not usually performed

Treatment Thrombolytics T-PA (alteplase) FDA approved for PE 100 mg infused over 2 hrs no difference in mortality or recurrent PE at 90 days compared to UFH

Treatment Surgical embolectomy requires a specialized center Can be safe Can be effective Small published numbers Catheter directed embolectomy Emerging as effective therapy when fibrinolysis cannot be used Can be performed up to 5 days after event

Thank you