Pulmonary Embolism (Clinical)

Overview

Definition

Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism (PE) is the intraluminal obstruction of a main pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy or any of its branches by a thrombus, air, amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity, or fat. When thrombotic PE is considered together with DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis, the condition is known as venous thromboembolic ( VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States) disease.

Epidemiology^[3]

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: approximately 112 per 100,000 in the United States
• Common in the elderly (> 500 per 100,000 in individuals > 75 years of age)
• Slight male predominance
• Relationship of PE with DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis:
  • 50% of untreated proximal DVTs lead to PE within 3 months.
  • > 90% of PEs PES Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (ppf), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. Thrombotic Thrombocytopenic Purpura are due to DVTs of the lower leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy.

Etiology and risk factors^[1]

The 3 primary factors that contribute to VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States (known as Virchow’s triad Virchow’s triad Deep Vein Thrombosis) include venous stasis, hypercoagulability Hypercoagulability Hypercoagulable States, and vascular endothelial damage. Any condition that worsens 1 (or more) of the 3 factors increases the risk of DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis formation and, thus, PE.

• Virchow’s triad Virchow’s triad Deep Vein Thrombosis (predictive for developing DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis):
  • Stasis
  • Endothelial injury
  • Hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States state
• Genetic:
  • Factor V Leiden Factor V Leiden Hypercoagulable States mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations
  • Prothrombin Prothrombin A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Hemostasis gene mutation Gene Mutation Myotonic Dystrophies
  • Protein C and Protein S Protein S Protein S augments the activity of protein C. Hemostasis deficiencies
  • Antithrombin deficiency Antithrombin deficiency An absence or reduced level of antithrombin III leading to an increased risk for thrombosis. Budd-Chiari Syndrome
• Acquired:
  • Immobilization Immobilization Delirium
  • Recent surgery (especially orthopedic surgery)
  • Malignancy Malignancy Hemothorax
  • Trauma 
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy exposure:
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Hormonal contraception
    • Hormone replacement therapy Hormone Replacement Therapy Hormone replacement therapy (HRT) is used to treat symptoms associated with female menopause and in combination to suppress ovulation. Risks and side effects include uterine bleeding, predisposition to cancer, breast tenderness, hyperpigmentation, migraine headaches, hypertension, bloating, and mood changes. Noncontraceptive Estrogen and Progestins
  • Medical conditions:
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Congestive heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
    • Autoimmune disease
    • Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome
    • Inflammatory bowel disease
    • Paroxysmal nocturnal hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions
    • Severe liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease

Pathophysiology

Anatomic locations of PE^[3]

• Saddle embolus Saddle embolus Emboli at the bifurcation of the main pulmonary artery. Pulmonary Embolism:
  • At the bifurcation of the main pulmonary trunk Pulmonary Trunk Truncus Arteriosus
  • May extend into the right or left main pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy
  • 3%–6% of all cases
  • 5% risk of mortality Mortality All deaths reported in a given population. Measures of Health Status
• Most emboli move beyond the bifurcation to smaller branches of a pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy:
  • Lobar branches
  • Segmental branches
  • Subsegmental branches
• Cases usually have multiple emboli

Pathophysiology^[3,4]

Ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing/perfusion (V/Q) mismatch:

• Obstruction of vascular flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure → results in dead space Dead space That part of the respiratory tract or the air within the respiratory tract that does not exchange oxygen and carbon dioxide with pulmonary capillary blood. Ventilation: Mechanics of Breathing ( ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing without perfusion)
• Inflammatory response, which leads to:
  • Vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure and bronchoconstriction in unaffected nearby areas → further decreases blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure (Q) and air flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure (V)
  • Decreased surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) production + atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis → shunting (perfusion without ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing) → worsens V/Q mismatch
• Abnormal gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange (due to dead space Dead space That part of the respiratory tract or the air within the respiratory tract that does not exchange oxygen and carbon dioxide with pulmonary capillary blood. Ventilation: Mechanics of Breathing and shunting), resulting in:
  • Hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome
  • ↑ Respiratory drive → hypocapnia and respiratory alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis
  • Note: Shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock may lead to hypercapnia Hypercapnia A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. Neonatal Respiratory Distress Syndrome and acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis.

Hemodynamic instability:

• Right-sided heart failure Right-Sided Heart Failure Ebstein’s Anomaly:
  • Increased pulmonary vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (PVR)
  • Decreased ejection from the right ventricle (RV) with subsequent increase in central venous pressure Central venous pressure The blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity. Central Venous Catheter ( CVP CVP The blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity. Central Venous Catheter)
  • Ultimately leads to prolonged RV strain, distention, and decreased contractility
• Left-sided heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR):
  • “Right heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) causes left heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR).”
  • Timing:
    • Occurs acutely with larger (i.e., central) emboli
    • Occurs later with emboli lodged in more peripheral pulmonary vessels
  • Mechanism:
    • ↓ RV ejection fraction Ejection fraction Cardiac Cycle (due to large emboli or right-sided heart failure Right-Sided Heart Failure Ebstein’s Anomaly) → 
    • ↓ Left ventricular end-diastolic volume End-diastolic volume Cardiac Cycle (LVEDV) → 
    • ↓ Cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics (CO), which manifests clinically as hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension and tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children

Pulmonary infarction:

• Occurs in about 10% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• Associated with small emboli in the segmental and subsegmental branches, causing ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage of lung tissue
• Produces:
  • An intense inflammatory response
  • Intra-alveolar hemorrhage (possible)

Clinical Presentation

Timeline^[3–5]

• Acute: immediate development of symptoms
• Subacute: development of symptoms within days to weeks
• Chronic:
  • No immediate symptoms
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship gradually develop pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension (over years).

Symptoms^[3–5,11]

Presentation varies significantly. High suspicion must be maintained given the risks of complications and mortality Mortality All deaths reported in a given population. Measures of Health Status.

• Can be asymptomatic (incidentally found on imaging)
• Massive PE presents with hemodynamic instability/ shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock.
• Most common symptom: dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea at rest and/or during exertion
• Pleuritic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Cough
• Hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis 
• Symptoms of DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis:
  • Calf pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and/or tenderness
  • Extremity swelling Swelling Inflammation
  • Palpable cord
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
  • Warmth

Physical exam findings^[3–5,11]

• Tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination
• Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• Rales Rales Respiratory Syncytial Virus and/or decreased breath sounds
• Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
• Loud second heart sound (P2)
• Jugular vein distension

Diagnosis

Note: Variation in diagnostic approach may occur based on availability of resources and practice location. Detailed information for different regions(US^[26] ,UK^[28], Europe^[29]) is available for review.

Diagnosis is primarily via imaging. The decision to obtain imaging is based on clinical suspicion, pretest probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability assessment (typically using the Modified Wells criteria), and D-dimer D-dimer Deep Vein Thrombosis levels.

Preliminary assessment

• Pulse oximetry: room-air oxygen saturation Oxygen Saturation Basic Procedures (O₂ sat) < 95%^[11,15]
• High-sensitivity D dimer (< 500 ng/mL is normal):^[11,12,16]
  • By-product of cross-linked fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis degradation → elevated levels indicate thrombus breakdown
  • > 95% sensitivity when negative (i.e., normal values) → a negative test effectively rules out VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States in most low-risk and moderate-risk cases
  • Low specificity → a positive test (elevated value) does not confirm VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States since any condition that causes clots to form can elevate D-dimer D-dimer Deep Vein Thrombosis levels (e.g., recent surgery, cancer, or sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock)
• Age-adjusted D-dimer D-dimer Deep Vein Thrombosis:^{[10,12,16,22,28,29]} 
  • Considered in those with low to low-intermediate probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of PE only (NOT in those with high-intermediate and high probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability)
  • D-dimer D-dimer Deep Vein Thrombosis levels increase with age, so a higher threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction increases specificity of the test.
  • Proposed adjustment: age (if > 50 years) x 10 = cutoff value in ng/mL ( fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis equivalent units)
  • An example: age (60 years) x 10 = 600 ng/mL (instead of the fixed cutoff level of 500 ng/mL)
• Other laboratory findings:^[5]
  • Arterial blood gas Arterial blood gas Respiratory Alkalosis (ABG) on room air may show:
    • Hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome
    • Hypocapnia
    • Respiratory alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis
    • Wide alveolar-arterial (A-a) gradient for oxygen (calculator: A-a O₂ gradient)
  • CBC: Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus may be present.
  • Troponins:^[5,29]
    • May be elevated in 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with moderate-to-large emboli.
    • Associated with an increased risk of mortality Mortality All deaths reported in a given population. Measures of Health Status
    • Normal results on highly sensitive assays have high negative predictive value Negative predictive value The NPV is the percentage of people with a negative test result who are actually disease free, among all people with a negative result regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests for excluding adverse in-hospital outcomes
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification natriuretic peptide ( BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation) or proBNP:^[5,16,29]
    • Assists in risk stratification → ↑ levels are associated with ↑ mortality Mortality All deaths reported in a given population. Measures of Health Status risk
    • Frequently increased in those with RV dysfunction (in those with PE)
  • Prothrombin time Prothrombin time Clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen; prothrombin; factor V; factor VII; and factor X. Hemostasis (PT), activated partial thromboplastin time Partial thromboplastin time The time required for the appearance of fibrin strands following the mixing of plasma with phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides). It is a test of the intrinsic pathway (factors VIII, IX, XI, and XII) and the common pathway (fibrinogen, prothrombin, factors V and X) of blood coagulation. Hemostasis (aPTT)
• Electrocardiography Electrocardiography Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body’s surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a cathode ray tube display. Electrocardiogram (ECG) ( ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)) may show:^[5,29]
  • Arrhythmia:
    • Sinus tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children is most common.
    • Atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation
  • Right heart strain pattern:^[29]
    • New right bundle branch block Right bundle branch block Bundle Branch and Fascicular Blocks
    • Right axis deviation
    • Inverted T waves in leads V1–V4
  • S1Q3T3 pattern (rare but pathognomonic):
    • Prominent S wave in lead I
    • Q wave in lead III
    • Inverted T wave T wave Electrocardiogram (ECG) in lead III

Scoring systems to determine the likelihood of PE 

These prediction tools (see tables below) are part of the preliminary assessment and help determine the probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of PE and the subsequent testing needed. These tools are not intended for use in pregnant women in whom a PE is suspected.

• Modified Wells criteria → rates PE as either likely or unlikely (2-tiered system)^[5,19,28]
• Traditional Wells criteria score:^[5,29]
  • Uses the same parameters as the Modified Wells criteria, but the interpretation rates PE as either low, intermediate, or high probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability (3-tiered system)
  • Calculator: Wells Criteria for Pulmonary Embolism 
  • Found to reduce unnecessary imaging.
  • Low- and intermediate-probability results can be correlated with D-dimer D-dimer Deep Vein Thrombosis results to determine the need for further testing.
• Geneva score:^[5,17]
  • Calculator: Geneva Score (Revised) for Pulmonary Embolism 
  • Considers clinical variables such as age, medical and surgical history, and examination findings
• PE rule out criteria (PERC) rule:^[5,18,28,29]
  • A list of 8 criteria that, if met MET Preoperative Care in a patient with low probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability for PE, rules out PE or recommends further testing
  • Calculator: PERC Rule for Pulmonary Embolism 
  • The risk or likelihood of PE (e.g., Wells score Wells score Deep Vein Thrombosis) must first be established.
  • Best used in the emergency department for those with low probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of PE to determine if D-dimer D-dimer Deep Vein Thrombosis or imaging is needed
• D-dimer D-dimer Deep Vein Thrombosis and YEARS criteria:^[10,16,22]
  • Based on the YEARS study, which uses variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables D-dimer D-dimer Deep Vein Thrombosis thresholds + select clinical items (found in Wells criteria) to determine the need for imaging
  • If none of the YEARS clinical criteria are met MET Preoperative Care, the D-dimer D-dimer Deep Vein Thrombosis threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction is 1000 ng/mL.
  • If at least 1 criterion is met MET Preoperative Care, the D-dimer D-dimer Deep Vein Thrombosis threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction is 500 ng/mL.
  • PE is ruled out if:
    • No YEARS item and a D-dimer D-dimer Deep Vein Thrombosis of < 1000 ng/mL
    • At least 1 YEARS item and a D-dimer D-dimer Deep Vein Thrombosis of < 500 ng/mL
  • Found to have 14% reduction in CT pulmonary angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery ( CTPA CTPA Pulmonary Function Tests) use

Imaging^[5,13,29]

Chest radiography:

• Nonspecific
• Findings may include:
  • Atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis or parenchymal abnormality
  • Effusion
  • Cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly
• Other rare findings:
  • Hampton’s hump: hump-shaped opacity Opacity Imaging of the Lungs and Pleura in the lung periphery (base is on the pleural side)
  • Westermark’s sign: cutoff of pulmonary vessels causes hyperlucency distally (due to oligemia)

Chest CT pulmonary angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery ( CTPA CTPA Pulmonary Function Tests) with contrast or spiral Spiral Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) CT:

• Current gold standard in diagnosing PE
• Best initial test if modified Wells score Wells score Deep Vein Thrombosis > 4
• Shows filling defects Filling Defects Imaging of the Intestines in the pulmonary vasculature
• Also provides information regarding other pulmonary structures that could be contributing to the individual’s signs and symptoms

Ventilation-perfusion (V/Q) scan

• 2nd-line diagnostic modality
• Used if CT scan is contraindicated, not available, or inconclusive
• Compares distribution of air in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy via inhalation of radioactive xenon gas (the ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing scan) and perfusion via labeled serum markers (the perfusion scan)
• PE shows areas of perfusion defects with normal ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing
• Scored as normal, low-, intermediate-, or high-probability of PE
• Major limitation: most individuals have indeterminate scans
• A normal chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests is required (otherwise, there is increased false positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests results).

Pulmonary angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery:

• Fluoroscopic image is obtained during direct injection of iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones contrast into the main pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy via a central catheter.
• Largely replaced by CTPA CTPA Pulmonary Function Tests, but used if:
  • CT scan is inconclusive
  • Planning a catheter-directed thrombolysis or embolectomy
• Diagnosis of PE is confirmed with a filling defect or an interruption in the vessel
• Carries the risk of contrast reaction and complications from catheter insertion (e.g., arrhythmia)

Magnetic resonance pulmonary angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery (MRPA):

• Not commonly used
• An option if CTPA CTPA Pulmonary Function Tests and V/Q scan cannot be performed
• Quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of images is affected by multiple factors; therefore, MRPA can be used only at sites with expertise in this imaging.

Tests in hemodynamically unstable individuals: Bedside imaging can be used to make a presumptive diagnosis of PE, which justifies the initiation of treatment.

• Bedside venous ultrasonography (US):
  • Used to look for DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis → if present, makes a presumptive diagnosis of PE
  • Findings:
    • Loss of normal venous compressibility detected using ultrasound probe Probe A device placed on the patient’s body to visualize a target Ultrasound (Sonography)
    • Turbulent or retrograde flow Retrograde flow Veins: Histology on Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) imaging
• Bedside echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA)→ findings to make a presumptive diagnosis of PE include:
  • New RV strain
  • Can show cardiac thrombus (“in transit” embolus)
  • Note:
    • Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) also provides prognostic information in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with confirmed PE.
    • Generally considered insensitive at diagnosing PE (which is why it is not part of routine diagnosis in hemodynamically stable patients Hemodynamically Stable Patients Blunt Chest Trauma).

The diagnostic process based on hemodynamic stability

The Wells criteria (traditional and modified), Geneva score, and YEARS criteria (which uses items from Wells criteria) are validated. The choice of a particular scoring system is influenced by clinical training and site of practice. The following approach integrates the use of the pretest probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability with clinical stability.

Hemodynamically stable:^[5,28,29]

Most cases of PE are hemodynamically stable (e.g., no signs of shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock), allowing time to assess the pretest probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability, as well as utilize PERC and D-dimer D-dimer Deep Vein Thrombosis testing.

• Low probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability:
  • Traditional Wells score Wells score Deep Vein Thrombosis < 2, modified Wells ≤ 4, Geneva score ≤ 3
  • An option is to review if PERC is applicable and if 8 criteria are fulfilled, PE is ruled out.
  • If PERC is not applicable, or is not used for assessment, proceed with D-dimer D-dimer Deep Vein Thrombosis testing:
    • D-dimer D-dimer Deep Vein Thrombosis normal (< 500): PE excluded
    • D-dimer D-dimer Deep Vein Thrombosis elevated: order CTPA CTPA Pulmonary Function Tests with contrast (or V/Q scan).
• Intermediate probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability:
  • Traditional Wells score Wells score Deep Vein Thrombosis 2–6, modified Wells ≤ 4, Geneva score 4–10
  • Obtain D-dimer D-dimer Deep Vein Thrombosis and follow-up the same as above.
• High probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability:
  • Traditional Wells score Wells score Deep Vein Thrombosis > 6, modified Wells > 4, Geneva score > 10
  • Order CTPA CTPA Pulmonary Function Tests with contrast.

Hemodynamically unstable:^[2,5,29]

Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension and/or overt shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock (e.g., systolic blood pressure ( SBP SBP Ascites) < 90 mm Hg for > 15 minutes) can occur in a minority of cases on initial presentation or during the course of treatment. Diagnosis and management occur simultaneously in hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma with a high possibility of PE. 

• Restoring hemodynamic stability should be prioritized:
  • Adequate perfusion (e.g., IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids, vasopressors Vasopressors Sepsis in Children)
  • Oxygenation
• Once the individual is stable:
  • Those with high probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of PE:
    • Empiric anticoagulation Anticoagulation Pulmonary Hypertension Drugs 
    • Obtain definitive imaging ( CTPA CTPA Pulmonary Function Tests, if not contraindicated).
  • Those with low to intermediate probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability, evaluation proceeds:
    • D-dimer D-dimer Deep Vein Thrombosis testing and imaging
    • Initiation of empiric anticoagulation Anticoagulation Pulmonary Hypertension Drugs is affected by the timing of diagnostic testing. 
    • Anticoagulation Anticoagulation Pulmonary Hypertension Drugs is started if imaging will take > 4 hours for patient at intermediate risk or > 24 hours for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at low risk.²
• Persistently unstable:
  • Diagnostic approach relies on the resources (such as cardiothoracic surgery, interventional radiology Interventional radiology Subspecialty of radiology that combines organ system radiography, catheter techniques and sectional imaging. Penetrating Abdominal Injury, intensive care) in the institution.
  • Bedside imaging (e.g., lower-extremity US) is done, and empiric treatment can be given after risk–benefit analysis.

PE diagnostic algorithm

Management and Prognosis

Note: Variation in management approaches may occur based on experience, availability of resources, and practice location. Detailed information for different regions (US, UK, Europe) is available for review.

Address the ABCs^[29]

Assess and treat any hemodynamic instability. A majority of individuals will either present in stable condition, or respond to initial resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome efforts.

• Airway Airway ABCDE Assessment: Ensure that the airway Airway ABCDE Assessment is open and protected.
• Breathing/respiratory support:
  • Supplemental oxygen Supplemental Oxygen Respiratory Failure therapy to improve O₂ sat > 95%
  • Nasal cannula Nasal Cannula Respiratory Failure, non-rebreather mask, mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing
• Circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment/hemodynamic support:
  • Small amount of IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids (avoid fluid overload, which worsens the effects of right-sided heart failure Right-Sided Heart Failure Ebstein’s Anomaly)
  • Vasopressors Vasopressors Sepsis in Children (typically norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS)
  • Selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions of cardiac drugs should be based on the presence and severity of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) and hemodynamics Hemodynamics The movement and the forces involved in the movement of the blood through the cardiovascular system. Vascular Resistance, Flow, and Mean Arterial Pressure.
    • Dobutamine Dobutamine A catecholamine derivative with specificity for beta-1 adrenergic receptors. Sympathomimetic Drugs (2–20 µg/kg/min) improves myocardial contractility.^[2,29]
    • Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS (0.2–1.0 µg/kg/min) is given with dobutamine Dobutamine A catecholamine derivative with specificity for beta-1 adrenergic receptors. Sympathomimetic Drugs to counter the vasodilatory effect of the latter.

Anticoagulation Anticoagulation Pulmonary Hypertension Drugs: initial treatment^[2]

Bleeding risk: Anticoagulation Anticoagulation Pulmonary Hypertension Drugs is the mainstay of treatment for PE, however, the risk of bleeding must be evaluated prior to starting therapy.^[24]  

• There is no particular index that reliably predicts bleeding risk; thus, clinical judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment is needed. 
• Among the tools that can be used:
  • HAS-BLED score (calculator) developed to estimate 1-year risk of major bleeding in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation^[23,25,29]
  • VTE-BLEED score (calculator) a tool developed to estimate VTE-specific bleeding risk; classifies patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship as “high” or “low” risk of bleeding.^[25]
• Risk and recommendations:
  • For those with low risk of bleeding (< 2% in the next 3 months): start anticoagulation Anticoagulation Pulmonary Hypertension Drugs
  • For those with moderate risk of bleeding: individualize treatment (assess risk–benefit ratio)
  • For those with contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to anticoagulation Anticoagulation Pulmonary Hypertension Drugs or unacceptable risk of bleeding: inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy ( IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy) filter placement

Anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants:

• Empiric anticoagulation Anticoagulation Pulmonary Hypertension Drugs (while awaiting results of diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests) should be:^[2]
  • Started in individuals with a low risk for bleeding and:
    • High-probability of PE
    • Intermediate probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of PE, in which diagnostic evaluation will likely be > 4 hours
    • Low probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of PE, in which diagnostic evaluation will likely be > 24 hours
  • Not given to those at unacceptably high risk for bleeding
  • Given on an individual basis for those at moderate risk for bleeding
• Options:
  • Low-molecular-weight heparin (LMWH) given SC for at least 5 days
    • Enoxaparin Enoxaparin Low-molecular-weight fragment of heparin, having a 4-enopyranosuronate sodium structure at the non-reducing end of the chain. It is prepared by depolymerization of the benzylic ester of porcine mucosal heparin. Therapeutically, it is used as an antithrombotic agent. Anticoagulants 1 mg/kg twice daily (preferred) or 1.5 mg/kg once daily
    • Dalteparin Dalteparin A low-molecular-weight fragment of heparin, prepared by nitrous acid depolymerization of porcine mucosal heparin. The mean molecular weight is 4000-6000 daltons. It is used therapeutically as an antithrombotic agent. Anticoagulants 200 units/kg once daily or 100 units/kg twice daily
  • Unfractionated heparin Unfractionated heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Anticoagulants ( UFH UFH A highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Anticoagulants):
    • Initial bolus, followed by a maintenance rate that is adjusted based on results of monitoring
    • Example regimen 1: 80 units/kg bolus, then 18 units/kg/hr
    • Example regimen 2: 5000-unit bolus followed by 1333 units/hour
    • Initial monitoring is typically every 6 hours with aPTT and/or anti–factor Xa activity
  • Indirect factor Xa inhibitor Indirect Factor Xa Inhibitor Anticoagulants: fondaparinux Fondaparinux Synthetic pentasaccharide that mediates the interaction of heparin with antithrombins and inhibits factor Xa; it is used for prevention of venous thromboembolism after surgery. Anticoagulants (dosed to patient weight and given SC)
    • 5 mg once daily (< 50 kg)
    • 7.5 mg once daily (50–100 kg)
    • 10 mg (> 100 kg)
  • Direct factor Xa inhibitors: rivaroxaban Rivaroxaban A morpholine and thiophene derivative that functions as a factor Xa inhibitor and is used in the treatment and prevention of deep-vein thrombosis and pulmonary embolism. It is also used for the prevention of stroke and systemic embolization in patients with non-valvular atrial fibrillation, and for the prevention of atherothrombotic events in patients after an acute coronary syndrome. Anticoagulants, apixaban Apixaban Anticoagulants (both approved for monotherapy for VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States), edoxaban Edoxaban Anticoagulants
    • Rivaroxaban Rivaroxaban A morpholine and thiophene derivative that functions as a factor Xa inhibitor and is used in the treatment and prevention of deep-vein thrombosis and pulmonary embolism. It is also used for the prevention of stroke and systemic embolization in patients with non-valvular atrial fibrillation, and for the prevention of atherothrombotic events in patients after an acute coronary syndrome. Anticoagulants 15 mg by mouth twice daily (initial dose)
    • Apixaban Apixaban Anticoagulants 10 mg by mouth twice daily (initial dose)
    • Edoxaban Edoxaban Anticoagulants 60 mg by mouth once daily (> 60 kg) or 30 mg once daily (< 60 kg), after an initial 5–10 days of heparin
    • These agents should not be used in hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma
  • Direct thrombin inhibitor Direct Thrombin Inhibitor Anticoagulants: dabigatran Dabigatran A thrombin inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Anticoagulants
    • 150 mg by mouth twice daily 
    • Requires an initial 5–10 days of heparin
    • Should not be used in hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma
  • Note: Warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants should not be used as initial treatment owing to the brief period of hypercoagulability Hypercoagulability Hypercoagulable States that occurs when starting it.
• Medication is selected based on clinician Clinician A physician, nurse practitioner, physician assistant, or another health professional who is directly involved in patient care and has a professional relationship with patients. Clinician–Patient Relationship experience, patient comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus, and patient preferences (including cost); preferred agents in specific populations include:
  • General population (hemodynamically stable, not pregnant, without cancer or creatinine clearance Creatinine clearance Kidney Function Tests [CrCl] < 30 mL/min):^[2,24]
    • LMWH
    • Fondaparinux Fondaparinux Synthetic pentasaccharide that mediates the interaction of heparin with antithrombins and inhibits factor Xa; it is used for prevention of venous thromboembolism after surgery. Anticoagulants
    • Rivaroxaban Rivaroxaban A morpholine and thiophene derivative that functions as a factor Xa inhibitor and is used in the treatment and prevention of deep-vein thrombosis and pulmonary embolism. It is also used for the prevention of stroke and systemic embolization in patients with non-valvular atrial fibrillation, and for the prevention of atherothrombotic events in patients after an acute coronary syndrome. Anticoagulants or apixaban Apixaban Anticoagulants
    • Edoxaban Edoxaban Anticoagulants or dabigatran Dabigatran A thrombin inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Anticoagulants (started after initial parenteral anticoagulation Anticoagulation Pulmonary Hypertension Drugs)
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care: LMWH (dose-adjusted)^[2,16,24]
  • Cancer:^[2,16]
    • LMWH
    • Factor Xa inhibitors: apixaban Apixaban Anticoagulants, rivaroxaban Rivaroxaban A morpholine and thiophene derivative that functions as a factor Xa inhibitor and is used in the treatment and prevention of deep-vein thrombosis and pulmonary embolism. It is also used for the prevention of stroke and systemic embolization in patients with non-valvular atrial fibrillation, and for the prevention of atherothrombotic events in patients after an acute coronary syndrome. Anticoagulants
  • Coronary artery Coronary Artery Truncus Arteriosus disease:^[2]
    • Warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants (after initial parenteral anticoagulation Anticoagulation Pulmonary Hypertension Drugs)
    • Factor Xa inhibitors: apixaban Apixaban Anticoagulants, rivaroxaban Rivaroxaban A morpholine and thiophene derivative that functions as a factor Xa inhibitor and is used in the treatment and prevention of deep-vein thrombosis and pulmonary embolism. It is also used for the prevention of stroke and systemic embolization in patients with non-valvular atrial fibrillation, and for the prevention of atherothrombotic events in patients after an acute coronary syndrome. Anticoagulants
  • Heparin-induced thrombocytopenia Heparin-Induced Thrombocytopenia Thrombocytopenia (HIT): non-heparin anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants^[24]
  • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome: IV UFH UFH A highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Anticoagulants^[24]
  • Extensive DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis or with phlegmasia cerulea dolens Phlegmasia cerulea dolens Near-total occlusion of the deep venous system resulting in venous gangrene. Acute Limb Ischemia, or massive PE: IV UFH UFH A highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Anticoagulants^[24]
  • Antiphospholipid syndrome Antiphospholipid syndrome Antiphospholipid syndrome (APLS) is an acquired autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies, which create a hypercoagulable state. These antibodies are most commonly discovered during a workup for a thrombotic event or recurrent pregnancy loss, which are the 2 most common clinical manifestations. Antiphospholipid Syndrome: heparin, then warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants (preferred for long-term anticoagulation Anticoagulation Pulmonary Hypertension Drugs)^[16]
• In other cases of PE:
  • Subsegmental PE: Proximal pulmonary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology are not involved.
    • Management varies per practice, and some recommend anticoagulation Anticoagulation Pulmonary Hypertension Drugs.^[14,27]
    • CHEST guidelines recommend surveillance Surveillance Developmental Milestones and Normal Growth (over anticoagulation Anticoagulation Pulmonary Hypertension Drugs) in those without DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis and without recurrent VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States risk.^[26]
    • In those at risk for recurrent VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States, anticoagulation Anticoagulation Pulmonary Hypertension Drugs is given.
  • Incidental or asymptomatic PE: anticoagulation Anticoagulation Pulmonary Hypertension Drugs
• Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
  • Active bleeding
  • Acute intracranial hemorrhage Intracranial hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most sahs originate from a saccular aneurysm in the circle of willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage
  • Major trauma
  • Severe bleeding disorders Bleeding disorders Hypocoagulable conditions, also known as bleeding disorders or bleeding diathesis, are a diverse group of diseases that result in abnormal hemostasis. Physiologic hemostasis is dependent on the integrity of endothelial cells, subendothelial matrix, platelets, and coagulation factors. The hypocoagulable states result from abnormalities in one or more of these contributors, resulting in ineffective thrombosis and bleeding. Hypocoagulable Conditions

Reperfusion therapy^[2,15]

More aggressive treatment is required in hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma or in those whose condition deteriorates despite initial anticoagulation Anticoagulation Pulmonary Hypertension Drugs.

• Thrombolytic therapy:
  • Infusion of a lytic agent (usually tissue plasminogen activator Tissue plasminogen activator A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to fibrinolysin. It has fibrin-binding activity and is immunologically different from urokinase-type plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. Hemostasis [ tPA tPA Ischemic Stroke])
  • Routes:
    • Systemic therapy
    • Catheter directed: a catheter tip directed at the embolus in an attempt to lyse the thrombus
  • Indications:
    • Hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma with a massive embolus
    • Hemodynamically stable patients Hemodynamically Stable Patients Blunt Chest Trauma with adverse outcomes (e.g., RV dysfunction)
    • Individuals unresponsive to systemic anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants with clear deterioration^[26]
• Embolectomy consists of removal of the embolus:
  • Catheter-based or surgical procedure
  • Indications:
    • Hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma with massive emboli, who are not suitable candidates for thrombolytic therapy (e.g., active bleeding)
    • In cases of failed thrombolytic therapy

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas assessment^[2,29]

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be assessed for their risk of early mortality Mortality All deaths reported in a given population. Measures of Health Status (within 30 days):

• All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with initial hemodynamic instability are at high risk, which can be defined as at least one of the following:
  • Cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest
  • Obstructive shock Obstructive Shock Types of Shock ( SBP SBP Ascites < 90 mm Hg or requiring vasopressors Vasopressors Sepsis in Children)
  • Persistent hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
• Tools to assess risk of early mortality Mortality All deaths reported in a given population. Measures of Health Status:
  • Original PE Severity Index (PESI): looks at 11 parameters to classify patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship into 5 classes from “very low risk” to “very high risk”
  • Simplified PE severity index (sPESI calculator): looks at 6 parameters to classify patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship simply as low or high risk^[2,29]
• Other poor prognostic indicators that elevate early mortality Mortality All deaths reported in a given population. Measures of Health Status risk:
  • RV dysfunction on TTE TTE Imaging of the Heart and Great Vessels or CTPA CTPA Pulmonary Function Tests
  • Elevated cardiac troponin levels
  • Elevated BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation
• Management location based on prognostic assessment:
  • Low-risk PE cases can be managed on an outpatient basis as long as outpatient access and home resources are adequate.^[24,26,28] 
  • Clinical consideration must be given to those with renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome and severe comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus (as sPESI will not be applicable to them).

Prophylaxis Prophylaxis Cephalosporins against recurrent PE

Anticoagulation Anticoagulation Pulmonary Hypertension Drugs: secondary prevention of VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States:^[8,16,26,27]

• Administered for 3‒6 months to prevent recurrence (some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may require lifelong therapy)
• Duration of therapy depends on risk factors for recurrence and bleeding.
• Decision on extending anticoagulation Anticoagulation Pulmonary Hypertension Drugs (beyond 3–6 months) needs to consider:
  • Risk of VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States recurrence: primarily based on whether PE was provoked or unprovoked and on whether risk factors are transient or persistent:
    • Unprovoked VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States: proceed with extended therapy 
    • Persistent risk factor: proceed with extended therapy
    • Transient risk factor: no extended therapy
  • Risk of bleeding
  • Patient values and preference
• Options:
  • LMWH
  • Vitamin K Vitamin K A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: vitamin K 1 (phytomenadione) derived from plants, vitamin K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, vitamin K 3 (menadione). Vitamin k 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin k. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin k. Fat-soluble Vitamins and their Deficiencies antagonists: warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants
    • Requires regular Regular Insulin monitoring of the prothrombin time Prothrombin time Clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen; prothrombin; factor V; factor VII; and factor X. Hemostasis (PT)
    • Numerous drug interactions
    • Contraindicated in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care (teratogenic)
  • Direct factor Xa inhibitors: rivaroxaban Rivaroxaban A morpholine and thiophene derivative that functions as a factor Xa inhibitor and is used in the treatment and prevention of deep-vein thrombosis and pulmonary embolism. It is also used for the prevention of stroke and systemic embolization in patients with non-valvular atrial fibrillation, and for the prevention of atherothrombotic events in patients after an acute coronary syndrome. Anticoagulants, apixaban Apixaban Anticoagulants, edoxaban Edoxaban Anticoagulants
    • Monitoring generally not required
    • More expensive
  • Thrombin Thrombin An enzyme formed from prothrombin that converts fibrinogen to fibrin. Hemostasis inhibitors: dabigatran Dabigatran A thrombin inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Anticoagulants
    • Prolongs aPTT
    • Similar to the direct factor Xa inhibitors; an option for those with a history of HIT
• Depending on the initial and secondary therapies, “bridging” may be required to ensure full anticoagulation Anticoagulation Pulmonary Hypertension Drugs during transition of therapy (e.g., continuing LMWH until warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants is effective based on the PT)
• Aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs):^[26]
  • CHEST guidelines indicate that anticoagulation Anticoagulation Pulmonary Hypertension Drugs is superior to aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) in those with an unprovoked PE.  
  • However, for those with an unprovoked PE who decide to stop anticoagulant therapy, aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) is suggested in order to prevent recurrence. 

IVC filter IVC filter Mechanical devices inserted in the inferior vena cava that prevent the migration of blood clots from deep venous thrombosis of the leg. Hypercoagulable States:^[2,29]

• Used to prevent recurrent PE in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis
• Barrier placed within the IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy to prevent passage of the migratory thrombus into the pulmonary arterial system
• Not useful for DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis in the upper extremities
• Indications:
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
  • Complications from or failed systemic anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
  • Poor cardiopulmonary reserve

Lifestyle/other options:^[29]

• Exercise
• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
• Control of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
• Avoid estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy (e.g., combined oral contraceptive pills Combined oral contraceptive pills Fixed drug combinations administered orally for contraceptive purposes. Hormonal Contraceptives) in high-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• Compression Compression Blunt Chest Trauma stockings

Long-term prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[3,10,29]

• Estimated mortality Mortality All deaths reported in a given population. Measures of Health Status:
  • Untreated PE: approximately 30%
  • Treated PE: 2%–11% 
• Recurrence:
  • More likely in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with unresolved risk factors (i.e., cancer)
  • Highest in the 1st 2 weeks after presentation 
• Chronic thromboembolic pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension (CTEPH) is a long-term sequela that rarely occurs:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship report progressive dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea and/or exercise intolerance.
  • May result from an undissolved thrombus or parenchymal damage

Summary

Review clinical presentation (history and examination) and determine if PE is a possible diagnosis. Determine hemodynamic stability and note that for hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma, diagnosis, and treatment occur simultaneously.

Initial assessment and therapy:

• O₂ saturation and vital signs
• Ensure adequate perfusion and oxygenation.
• D-dimer D-dimer Deep Vein Thrombosis
• CBC, metabolic panel, PT, aPTT (and additional labs depending on underlying conditions)
• Arterial blood gas Arterial blood gas Respiratory Alkalosis
• Troponins I and T
• BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation and/or proBNP
• ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)
• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests (can be performed bedside if patient is unstable)

For the hemodynamically unstable patient after initial resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome with high suspicion of PE:

• Coordinate available resources: PE response team, intensive care, cardiothoracic surgery, interventional radiology Interventional radiology Subspecialty of radiology that combines organ system radiography, catheter techniques and sectional imaging. Penetrating Abdominal Injury, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).
• Bedside imaging to make a presumptive diagnosis of PE:
  • Bedside US (look for lower-extremity DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis)
  • Bedside echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) (look for RV dysfunction and/or thrombus in the heart)
• Empiric anticoagulation Anticoagulation Pulmonary Hypertension Drugs (if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation)
• Prompt diagnostic imaging if possible ( CTPA CTPA Pulmonary Function Tests, if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation)
• If PE is confirmed:
  • Ensure adequate perfusion and oxygenation.
  • Consider reperfusion therapy (thrombolytic therapy if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation).

For hemodynamically stable patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and those stabilized after initial resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome, calculate pretest probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability (e.g., Wells criteria):

• Low probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability → calculate PERC (some go straight to D-dimer D-dimer Deep Vein Thrombosis):
  • If PERC met MET Preoperative Care → no further testing
  • If PERC not met MET Preoperative Care → order/look at D-dimer D-dimer Deep Vein Thrombosis:
    • Elevated D-dimer D-dimer Deep Vein Thrombosis → imaging ( CTPA CTPA Pulmonary Function Tests if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation)
    • Normal → no further testing (search for other etiology)
• Intermediate probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability → look at D-dimer D-dimer Deep Vein Thrombosis
  • Elevated D-dimer D-dimer Deep Vein Thrombosis → imaging ( CTPA CTPA Pulmonary Function Tests if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation)
  • Normal → no further testing (search for other etiology)
• High probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability → CTPA CTPA Pulmonary Function Tests if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation
• If PE is confirmed:
  • Pretreatment evaluation:
    • Assess bleeding risk (clinical history, HAS-BLED score or VTE-BLEED score)
    • Assess PE severity/risk of early mortality Mortality All deaths reported in a given population. Measures of Health Status ( comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus, sPESI, RV dysfunction, elevated troponins or BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation)
  • Treatment:
    • Anticoagulate if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation (option depends on underlying conditions and risk) 
• IVC filter IVC filter Mechanical devices inserted in the inferior vena cava that prevent the migration of blood clots from deep venous thrombosis of the leg. Hypercoagulable States if patient has contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to anticoagulation Anticoagulation Pulmonary Hypertension Drugs

Differential Diagnosis

• Acute heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR): an acute reduction in cardiac function. Acute heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) commonly presents with dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, low room-air O₂ saturation levels, and lower-extremity edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, which is more likely to be bilateral as opposed to unilateral. Elevated  BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation and troponin levels are commonplace and echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) findings aid in the diagnosis. Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests may show pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema. Management relies on medical optimization.
• Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction: acute ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage of the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy. Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction can result in tachyarrhythmia Tachyarrhythmia A tachyarrhythmia is a rapid heart rhythm, regular or irregular, with a rate > 100 beats/min. Tachyarrhythmia may or may not be accompanied by symptoms of hemodynamic change. Tachyarrhythmias, right- and/or left-sided heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), and hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension depending on the severity and location. The chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that occurs during a heart attack Heart attack Mi is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction is most commonly substernal in location and not usually pleuritic. Serially elevated cardiac enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes and ST-segment changes on the ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) are usually diagnostic. Management involves stabilization, anticoagulant, and reperfusion therapies.
• Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia: an inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the lung parenchyma caused by respiratory infection. Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia may cause pleuritic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways with accompanying low room-air O₂ saturation levels. Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests commonly reveals parenchymal lesions, which are usually absent in PE unless a parenchymal infarct Infarct Area of necrotic cells in an organ, arising mainly from hypoxia and ischemia Ischemic Cell Damage is present. Treatment is with antibiotics and respiratory support in advanced cases.
• Chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)) exacerbation: an acute exacerbation of chronic disease of the lower respiratory tract causing respiratory impairment. COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) presents with marked dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea and is commonly accompanied by wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing. Chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is an unlikely symptom in the absence of concomitant pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia. Diagnosis is established based on a combination of history, clinical symptoms, and pulmonary function tests. Symptoms generally improve with supplemental oxygen Supplemental Oxygen Respiratory Failure therapy and a combination of steroidal treatments.