pulmonary embolism pulmonary embolism pulmonary embolism (pe) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). symptoms of a pe may include shortness of breath, chest pain particularly upon breathing in, and coughing up blood. symptoms of a blood clot in the leg may also be present, such as a red, warm, swollen, and painful leg. signs of a pe include low blood oxygen levels, rapid breathing, rapid heart rate, and sometimes a mild fever. severe cases can lead to passing out, abnormally low blood pressure, obstructive shock, and sudden death. pulmonary embolisma lung illustration depicting a pulmonary embolism as a thrombus (blood clot) that has travelled from another region of the body, causes occlusion of the pulmonary bronchial artery, leading to arterial thrombosis of the superior and inferior lobes in the left lungspecialtyhematology, cardiology, pulmonologysymptomsshortness of breath, chest pain, coughing up bloodcomplicationspassing out, abnormally low blood pressure, sudden death; chronic thromboembolic pulmonary hypertension (long-term complication)usual onsetadvanced agerisk factorscancer, prolonged bed rest, blunt trauma, smoking, stroke, certain genetic conditions, estrogen-based medication, pregnancy, obesity, after surgerydiagnostic methodbased on symptoms, d-dimer, ct pulmonary angiography, lung ventilation/perfusion scantreatmentanticoagulants (heparin, warfarin, doacs)frequency~450,000 per year (usa), 430,000 (europe)deaths>10–12,000 per year (us), >30–40,000 per year (europe) pe usually results from a blood clot in the leg that travels to the lung. the risk of blood clots is increased by advanced age, cancer, prolonged bed rest and immobilization, smoking, stroke, long-haul travel over 4 hours, certain genetic conditions, estrogen-based medication, pregnancy, obesity, trauma or bone fracture, and after some types of surgery. a small proportion of cases are due to the embolization of air, fat, or amniotic fluid. diagnosis is based on signs and symptoms in combination with test results. if the risk is low, a blood test known as a d-dimer may rule out the condition. otherwise, a ct pulmonary angiography, lung ventilation/perfusion scan, or ultrasound of the legs may confirm the diagnosis. together, deep vein thrombosis and pe are known as venous thromboembolism (vte). efforts to prevent pe include beginning to move as soon as possible after surgery, lower leg exercises during periods of sitting, and the use of blood thinners after some types of surgery. treatment is with anticoagulants such as heparin, warfarin or one of the direct-acting oral anticoagulants (doacs). these are recommended for at least three months. severe cases may require thrombolysis using medication such as tissue plasminogen activator (tpa) given intravenously or through a catheter, and some may require surgery (a pulmonary thrombectomy). if blood thinners are not appropriate, a temporary vena cava filter may be used. pulmonary emboli affect about 430,000 people each year in europe. in the united states, between 300,000 and 600,000 cases occur each year, which contribute to at least 40,000 deaths. rates are similar in males and females. they become more common as people get older. signs and symptoms symptoms of pulmonary embolism are typically sudden in onset and may include one or many of the following: dyspnea (shortness 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 because of decreased blood flow through the lungs and into the left side of the heart. about 15% of all cases of sudden death are attributable to pe. while pe may present with syncope, less than 1% of syncope cases are due to pe. on physical examination, the lungs are usually normal. 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 exudative, detectable by decreased percussion note, audible breath sounds, and vocal resonance. strain on the right ventricle may be detected as a left parasternal heave, a loud pulmonary component of the second heart sound, and/or raised jugular venous pressure. a low-grade fever may be present, particularly if there is associated pulmonary hemorrhage or infarction. as smaller pulmonary emboli tend to lodge in more peripheral areas without collateral circulation, they are more likely to cause lung infarction and small effusions (both of which are painful), but not hypoxia, dyspnea, or hemodynamic instability such as tachycardia. larger pes, which tend to lodge centrally, typically cause dyspnea, hypoxia, low blood pressure, fast heart rate and fainting, but are often painless because there is no lung infarction due to collateral circulation. the classic presentation for pe with pleuritic pain, dyspnea, and tachycardia is likely caused by a large fragmented embolism causing both large and small pes. thus, small pes are often missed because they cause pleuritic pain alone without any other findings and large pes are often missed because they are painless and mimic other conditions often causing ecg changes and small rises in troponin and brain natriuretic peptide levels. pes are sometimes described as massive, submassive, and nonmassive depending on the clinical signs and symptoms. although the exact definitions of these are unclear, an accepted definition of massive pe is one in which there is hemodynamic instability. this is a cause of obstructive shock, which presents as sustained low blood pressure, slowed heart rate, or pulselessness. risk factors a deep vein thrombosis as seen in the right leg is a risk factor for pe about 90% of emboli are from a deep vein thrombosis located above the knee termed a proximal dvt, which includes an iliofemoral dvt. the rare venous thoracic outlet syndrome can also be a cause of dvts, especially in young men without significant risk factors. dvts are at risk for dislodging and migrating to the lung circulation. the conditions are generally regarded as a continuum known as a venous thromboembolism (vte). vte is much more common in immunocompromised individuals as well as individuals with comorbidities including: those that undergo orthopedic surgery at or below the hip without prophylaxis. this is due to immobility during or after the surgery, as well as venous damage during the surgery. pancreatic and colon cancer patients (other forms of cancer also can be factors, but these are the most common) this is due to the release of procoagulants. risk of vte is at its greatest during diagnosis and treatment, but lowers in remission. patients with high-grade tumors pregnant individuals as the body puts itself into what is known as a "hypercoagulable state" the risk of a hemorrhage during childbirth is decreased and is regulated by increased expression of factors vii, viii, x, von willebrand, and fibrinogen. those on estrogen medication 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 properties of the blood). often, more than one risk factor is present. alterations in blood flow: immobilization (after surgery, long-haul flight), injury, pregnancy (also procoagulant), obesity (also procoagulant), cancer (also procoagulant) factors in the vessel wall: surgery, catheterizations causing direct injury ("endothelial injury") factors affecting the properties of the blood (procoagulant state): estrogen-containing medication (transgender hormone therapy, menopausal hormone therapy and hormonal contraceptives) 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) although most pulmonary embolisms are the result of proximal dvts, there are still many other risk factors that can also result in a pulmonary embolism. risk factors include: varicose veins caused by vascular damage pulmonary hypertension diabetes traumatic hip fractures that immobilize the patient joint fixation (primarily in the legs) underlying causes after a first pe, the search for secondary causes is usually brief. only when a second pe occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. this will include testing ("thrombophilia screen") for factor v leiden mutation, antiphospholipid antibodies, protein c and s and antithrombin levels, and later prothrombin mutation, mthfr mutation, factor viii concentration and rarer inherited coagulation abnormalities. diagnosis a hampton hump in a person with a right lower lobe pulmonary embolism to diagnose a pulmonary embolism, a review of clinical criteria to determine the need for testing is recommended. in those who have low risk, age less than 50, heart rate less than 100 beats per minute, oxygen level more than 94% on room air, and no leg swelling, coughing up of blood, surgery or trauma in the last four weeks, previous blood clots, or estrogen use, further testing is not typically needed. in situations with more high risk individuals, further testing is needed. a ct pulmonary angiogram (ctpa) is the preferred method for diagnosis of a pulmonary embolism due to its easy administration and accuracy. although a ctpa is preferred, there are also other tests that can be done. for example, a proximal lower limb compression ultrasound (cus) can be used. this is a test which is primarily used as a confirmatory test, meaning it confirms a previous analysis showing the presence or suspected presence of a pulmonary embolism. according to a cross-sectional study, cus tests have a sensitivity of 41% and specificity of 96%. if there are concerns this is followed by testing to determine a likelihood of being able to confirm a diagnosis by imaging, followed by imaging if other tests have shown that there is a likelihood of a pe diagnosis. the diagnosis of pe is based primarily on validated clinical criteria combined with selective testing because the typical clinical presentation (shortness of breath, chest pain) cannot be definitively differentiated from other causes of chest pain and shortness of breath. the decision to perform medical imaging is based on clinical reasoning, that is, the medical history, symptoms, and findings on physical examination, followed by an assessment of clinical probability. probability testing the most commonly used method to predict clinical probability, the wells score, is a clinical prediction rule, whose use is complicated by multiple versions being available. in 1995, philip steven wells, initially developed a prediction rule (based on a literature search) to predict the likelihood of dvt, based on clinical criteria. a new prediction score for pe was created in 1998 this prediction rule was revised by wells et al. in 2000. in the 2000 publication, wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule, and also included d-dimer testing in the rule-out of pe in low probability patients. in 2001, wells published results using the more conservative cutoff of 2 to create three categories. an additional version, the "modified extended version", using the more recent cutoff of 2 but including findings from wells's initial studies were proposed. most recently, a further study reverted to wells's earlier use of a cutoff of 4 points to create only two categories. there are additional prediction rules for pe, such as the geneva rule. more importantly, the use of any rule is associated with reduction in recurrent thromboembolism. the wells score: clinically suspected dvt – 3.0 points alternative diagnosis is less likely than pe – 3.0 points tachycardia (heart rate > 100) – 1.5 points immobilization (≥ 3d)/surgery in previous four weeks – 1.5 points history of dvt or pe – 1.5 points hemoptysis – 1.0 points malignancy (with treatment within six months) or palliative – 1.0 points traditional interpretation score >6.0 – high (probability 59% based on pooled data) score 2.0 to 6.0 – moderate (probability 29% based on pooled data) score <2.0 – low (probability 15% based on pooled data) alternative interpretation score > 4 – pe likely. consider diagnostic imaging. score 4 or less – pe unlikely. consider d-dimer to rule out pe. recommendations for a diagnostic algorithm were published by the pioped investigators; however, these recommendations do not reflect research using 64 slice mdct. these investigators recommended: low clinical probability. if negative d-dimer, pe is excluded. if positive d-dimer, obtain mdct and base treatment on results. moderate clinical probability. if negative d-dimer, pe is excluded. however, the authors were not concerned that a negative mdct with negative d-dimer in this setting has a 5% probability of being false. presumably, the 5% error rate will fall as 64 slice mdct