Pulmonary Thromboembolism Prof. Sevda Özdoğan MD Chest Diseases

Learning Objectives: Define pulmonary embolism, the source in thromboembolism and pathophysiology Define the importance of diagnosis in pulmonary tromboembolism List the acquired risk factors of Pulmonary Embolism Explain the genetic risk factors and whom they should be suspected Define the clinical syptoms and physical examination findings of Pulmonary embolism List the diagnostic methods in pulmonary embolism Define the systematic diagnostic approach to a suspected pulmonary embolism patient

List the chest x ray finding in pulmonary embolism Define the findings in arterial blood gas and echocardiography in pulmonary embolism Explain the interpretation of definite diagnostic procedures in pulmonary embolism List the diagnostic methods of Deep Venous Thrombosis Define the principles of treatment and prophylaxis of pulmonary embolism

Pulmonary Thromboembolism Pulmonary embolism is caused by the obstruction of the pulmonary arteries by clots from the veins of the systemic circulation that embolise to lungs Obstructive material other than blood (fat, amnion fluid etc) can also cause pulmonary embolism in certain situations but venous thromboembolism (VTE) is the most common cause

Epidemiology In USA there are new case /year and the incidence rate is higher among older age groups The mortality rate was reported as 51/ in 1995 Mortality rate is very high in the first hour

Among the survivors after the first hour 2/3 of the patients remain undiagnosed The mortality for this group is around 30% With the right diagnosis and treatment this rate declines to 3-8% % 90 of the thrombus comes from the lower extremities

Pathophysiology Virchow Triade 1. Venous stasis 2. Vascular endothelial (wall) damage 3. Hypercoagulation

Risk factors GeneticAcquired Antithrombin III deficiency Autosomal dominant Risk of VTE x5 DVT Previous PE 30% DVT pts develop symptomatic PE 50%-60% DVT pts develop asymptomatic PE Protein C and S (cofactor) deficiency Autosomal dominant Risk od VTE x6 Age 40 years or more Activated protein C (APC) resistance Factor V Leiden mutation Positive in 21% of VTE patients Surgery and trauma* (Lover extremity fracture or surgery, Neurosurgery) Blood stasis due to immobilization General anesthetic disturbs the balance of coagulation factors and their inhibitors Local tissue trauma, vessel damage Prothrombin G20210A A single nucleotide change in prothrombin gene results in elevated prothrombin levels Risk of DVT x5 Medical conditions Left ventricular failure Malignancy Nephrotic syndrome Stroke Crohn disease Previous VTE Hyperhomocystine mia Defects in enzymes of homocystein disposal Risk of VTE x2 Oral contraceptives Estrogen content increases the risk x7 If heterozygot Fac V leiden mut. Than x30

GeneticAcquired Increased Factor VIII RR for VTE x4.8 Smoking Cause the vessel wall damage Blood group other than O RR of DVT x2 Pregnancy Hypercoagulability Venous stasis Combination of the genetic risk factors Platelet abnormalities Polistemia vera Obesity

Testing for genetic risk factors is considered in patients who have: VTE at a young age Family history of VTE No evidence of acquired risk factors PE that originates from a spontaneous venous thrombosis other than leg vein thrombosis

Clinical features and Diagnosis Clinical suspicion*** Medical history: To identify the patient at risk Family history Medical or acquired risk factors Symptomatology:

Unexplained acute dyspnea Tachypnea Substernal chest discomfort Pleuretic chest pain Cyanosis Shock / sencope Fever Hemopthysis Asymptomatic 97%

Tachycardia, tachypnea Pleural rub Late inspiratory rales, wheese İncreased pulmonary component of the second heart sound (p2) Right ventricular S3 Elevated jugular venous pulse Tender liver Fever (in infarction) Physical findings: (nonspecific)

Diagnostic approach There are significant difficulties in the accurate diagnosis of pulmonary embolism as there is a broad differential diagnosis. PE can present in a variety of ways depending on the size, location, number of emboli and the underlying condition of the patient. Objective diagnostic test result are needed for definite diagnosis of VTE and deep venous thrombosis (DVT)

Diagnostic approach Semptomatology and signs Chest radiology Arterial blood gas analysis (ABG) Electrocardiography Standard laboratory tests Echocardiography (Cardiac and venous doppler of the lower extremity) D-Dimer Spiral CT Ventilation / perfusion scan Pulmoner angiography (gold standard) MRI

Estimating Clinical Probability of Pulmonary Embolism High Risk factor present (80-100% probable)Otherwise unexplained dyspnea, tachypnea, or pleuritic chest pain Otherwise unexplained radiographic or gas exchange abnormality Intermediate Neither high nor low clinical probability (20-79% probable) Low Risk factor not present (1-19% probable)Dyspnea, tachypnea, or pleuritic pain possibly present but explainable by another condition Radiographic or gas exchange abnormality possibly present but explainable by another condition

Chest Radiography Negative chest radiogram is a common presentation so does’t exclude the diagnosis 80% Abnormal chest radiograph but nonspecific Peripheral regional oligemia (Westermark’s sign) (7%) A prominant pulmonary hilus with little tapering of vessels (Fleischner’s sign) (15%) Peripheral wedge shaped densities (Hampton’s hump) (35%) Plate like atelectasis Diaphragmatic elevation (%24) Pleural effusion (%48)

Linear atelectasis Pulmonary infarct

Frontal chest radiograph obtained from a patient with an acute pulmonary embolism. The left pulmonary artery is enlarged (small arrow), and a wedge-shaped peripheral opacity is present at the left costophrenic angle (large arrow)

ABG Analysis Hypoxemia, hypocapnia and respiratory alcalosis PaO 2 <%80 PaO 2 may be normal in submassive embolism if no underlying pulmonary disease is present (A-a)O 2 gradient is increased in almost all the patients

ECG Abnormalities of ECG are nonspecific Acute right ventricular strain in massive embolism Sinus tachicardia Negative T wave and/or ST segment depression in leads V1-3 S 1 Q 3 T 3 patern (Deep S wave in lead D1, deep Q wave in lead D3, inverted T waves in D3) Right bundle branch block (complete or incomplete) P-pulmonale Changes can be similar to MI

Standard laboratory tests Nonspecific changes WBC can be slightly elevated LDH, bilirubine can be slightly elevated D-Dimer (fibrin degradation product) can be elevated ELISA or Latex agglutination Sensitivity % but specificity is low <500 ng/ml PE can be excluded if there is also low clinical probability Elisa is more sensitive but slow compared to Latex

ECHOCARDIOGRAPHY (Doppler) Can be performed rapidly at the bedside Features that suggest acute massive PE include A dilated, hypokinetic right ventricle With the absence of right ventricular hypertrophy Distortion of the interventriculer septum toward the left ventricle Tricuspit regurgitation the elevation of pulmonary artery pressure Identified trombi in the central pulmonary arteries Absence of significant pathologic left ventricular conditions

Spiral Computed Tomography Angiography (SCTA) Allows rapid investigation of the pulmonary vasculature at peak contrast opasification within a single breath hold Three dimentional reconstruction is possible Sensitivity and specificity is around 90% up to subsegmental defects May demonstrate or exclude other abnormalities in the lung Bolus contrast is used for the visualization of the pulmonary vasculature Filling defects are diagnostic

Partial filling defect in right middle lobe and lover lobe artery Wedge shaped infiltration on the right upper lobe posterior segment

Sagital-oblique CT image showing thrombus narrowing left lover lobe pulmonary artery

Ventilation-Perfusion Scintigraphy Detection of the perfusion abnormalities subsequent to the embolic event Classically to display that a segment distal to an obstructing embolus is not perfused but is still ventilated 99 Tc is usually used for perfusion and 133 Xe for ventilation scaning. The two studies are analysed together. In clinical practice the results of V/Q scintigraphy are interpreted together with the clinical estimate of the likelihood of acute PE A normal V/Q virtually excludes clinically relevant PE

Patient with multiple embolisms in both lungs: segmental mismatch defect in left lung was detected by both SPECT (A and B) and planar scintigraphy (C and D). Defects are marked by arrows in B and D. Subsegmental mismatch defects are present in right lung. CT angiography found thrombotic clots in branches of middle lobe artery and both lower lobe arteries

Estimate of the likelihood of PE Normal Perfusion (Q): exclude PE Q defects—Ventilation (V) is normal on these regions: (V/Q mismatch defect) High probability of PE If Chest x ray is normal on the regions of V/Q mismatch: higher probability If V/Q mismatch areas are segmental or larger: higher probability Q defects—V defect on these regions: (V/Q match defect) Low probability, undetermined

MRI Magnetic resonance angiography with the use of contrast material can demonstrate the pulmonary arteries beyond the segmental level A potential advantage is that it allows the study of the pulmonary arteries and the deep veins of the lower extremities within a single examination

Pulmonary Angiography (gold standard) Detects emboli in the subsegmental or even more peripheral arteries Unfortunately it is invasive and there is lack of availability in an urgent investigation Can be used if V/Q scan is nondiagnostic and the clinical probability is high Not performed if perfusion scintigraphy is normal Mortality %0,5 Major complications %0,4

Deep Venous Thrombosis (DVT) Compression ultrasound Doppler ultrasonography Venography (gold standard)

Suspect Pulmonary Embolism ? Give heparin IV and order V/Q scan Low V/Q probability, low clinical probability High V/Q probability + high clinical probability Intermediate V/Q probability, Low or high V/Q prob with discordant clinical probability Probability V/Q Clinical 1. Low Mid 2. Mid Low No treatment Probability V/Q Clinical 3. Low High 4. Mid Mid / High 5. High Low / Mid Leg UltrasoundTreat _ Pulmonary Angiography + + Am J Respir Crit Care Med. Vol 159: 1-14; 1999 BT BT (-) BT (-) high cl prob. BT (+)

Treatment of PTE and DVT Supportive treatment Oxygen Intravenous fluid Vasopressor agents Resuscitary measures depending on the clinical status of the patient Anticoagulant therapy Unfractionated heparin (UFH) Low molecular weight heparin (LMWH) Oral anticoagulants (Warfarin) Thrombolytic treatment Vena Cava Filters Surgical treatment

Treatment duration Reversible risk factor, first event, age<60 : 3-6 months Reversible risk factor, first event, age>60: 6-12 months First event, unknown risk factor: 6-12 months Recurrent event: >12months- life long Irreversible risk factor, first event: >12 months- life long

Primary Prevention Determined by the thrombotic risk of the clinical situation in conjunction with the patients profile of risk factors Ortopedic surgery (post-traumatic) ICU Neurosurgery carry the highest risk LMWH or UFH can be used LMWH’s can be used preoperatively safely Prophylaxis should be continued up to 4 weeks after surgery

Patients with congenital risk factors: Homozygot : Lifelong anticoagulation Heterozygot: During the periods of high risk Recurrent embolism or continious risk factor: lifelong anticoagulation

Non medical Prophylaxis Graduated compression stockings İntermittent pneumatic compression Foot impulse pumps Can be used for patients who have contraindications to anticoagulants.