Pulmonary thromboembolism REF: Harrison's Internal Medicine 17th edition Chapter 256. Deep Venous Thrombosis and Pulmonary Thromboembolism PULMONARY THROMBOEMBOLISM: Pathophysiology When venous thrombi dislodge from their site of formation, they embolize to the pulmonary aerial circulation or, paradoxically, to the aerial circulation through a patent foramen ovale or atrial septal defect. About half of patients with pelvic vein thrombosis or proximal leg DVT develop PE, which is usually asymptomatic. With increased use of chronic indwelling central venous catheters for hyperalimentation and chemotherapy, as well as more frequent inseion of permanent pacemakers and internal cardiac defibrillators, upper extremity venous thrombosis is becoming a more common problem. These thrombi rarely embolize and cause PE. Pathophysiological abnormalities include: The most common gas exchange abnormalities are hypoxemia (decreased aerial P02) and an increased alveolar-aerial 02 tension gradient, which represents the inefficiency of 02 transfer across the lungs Increased pulmonary vascular resistance due to vascular obstruction or platelet secretion of vasoconstricting neurohumoral agents such as serotonin. Impaired gas exchange due to increased alveolar dead space from vascular obstruction, hypoxemia from alveolar hypoventilation relative to perfusion in the nonobstructed lung, right-to-left shunting, and impaired carbon monoxide transfer due to loss of gas exchange surface. Alveolar hyperventilation due to reflex stimulation of irritant receptors Increased airway resistance due to constriction of airways distal to the bronchi Decreased pulmonary compliance due to lung edema, lung hemorrhage, or loss of surfactant Signs & Symptoms Sudden-onset dyspnea (shoness of breath) Tachypnea (rapid breathing) Chest pain of a "pleuritic" nature (worsened by breathing) Cough and hemoptysis (coughing up blood). More severe cases can include signs such as cyanosis (blue discoloration, usually of the lips and fingers), collapse, and circulatory instability due to decreased blood flow through the lungs and into the left side of the hea. Occasionally, a pleural friction rub may be audible over the affected area of the lung (mostly in PE with infarct) A pleural effusion is sometimes present that is transudative A low-grade fever may be present, paicularly if there is associated pulmonary hemorrhage or infarction About 15% of all cases of sudden death are attributable to PE Risk factors The most common sources of embolism are proximal leg deep venous thrombosis (DVTs) or pelvic vein thromboses. The development of thrombosis is classically due to a group of causes named Virchow's triad (alterations in blood flow, factors in the vessel wall and factors affecting the propeies of the blood). Often, more than one risk factor is present. Alterations in blood flow: immobilization (after surgery, injury or long-distance air travel), pregnancy (also procoagulant), obesity (also procoagulant), cancer (also procoagulant) Factors in the vessel wall: of limited direct relevance in VTE Factors affecting the propeies of the blood (procoagulant state) Estrogen-containing hormonal contraception Genetic thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and plasminogen/fibrinolysis disorders) Acquired thrombophilia (antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria) Cancer (due to secretion of pro-coagulants) Diagnosis D-dimer is highly sensitive but not very specific (specificity around 50%). In other words, a positive D-dimer is not synonymous with PE, but a negative D-dimer is, with a good degree of ceainty, an indication of absence of a PE The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography CT pulmonary angiography (CTPA) is a pulmonary angiogram obtained using computed tomography (CT) with radiocontrast rather than right hea catheterization. Its advantages are clinical equivalence, its non-invasive nature, its greater availability to patients Ventilation/perfusion scan (or V/Q scan or lung scintigraphy), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in patients who have an allergy to iodinated contrast or in pregnancy due to lower radiation exposure than CT