Deep Vein Thrombosis (Clinical)

Epidemiology and Risk Factors

Epidemiology^[4,5]

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of 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: 1 per 1,000 population
• 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 is slightly higher in males and increases with age.
• Proximal deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus (DVTs) are more likely to cause 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).
  • 10% of proximal 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 vein DVTs will lead to PE.
  • 50% of untreated proximal DVTs will 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 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 DVTs.

Risk Factors^[1,4,5]

The 3 primary factors (known as the Virchow triad) that contribute to 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 include: venous stasis, hypercoagulability Hypercoagulability Hypercoagulable States, and vascular endothelial damage. Any condition which worsens one (or more) of these three 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.

Factors resulting in endothelial damage:

• Hypertension: Increased shear stress leads to damage of the endothelium.
• Surgery
• Vascular catheter placement (e.g., hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome catheters, peripherally inserted central catheters [PICC] lines): most common cause of upper 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
• Trauma and burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns, especially involving the vasculature
• 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
  • Leads to loss of anticoagulant proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (e.g., antithrombin Antithrombin Endogenous factors and drugs that directly inhibit the action of thrombin, usually by blocking its enzymatic activity. They are distinguished from indirect thrombin inhibitors, such as heparin, which act by enhancing the inhibitory effects of antithrombins. Anticoagulants, proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis C and S) via the urine due to damaged glomerular membranes
  • Leads to an increase in the production of 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 and other procoagulant proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis in the 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 due to protein loss and hypoalbuminemia Hypoalbuminemia A condition in which albumin level in blood (serum albumin) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (albuminuria). Nephrotic Syndrome in Children

Factors resulting in venous stasis:

• Immobilization Immobilization Delirium (e.g., long air travel, after orthopedic surgery): 20 times increased risk of developing a 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
• 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)
• Polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma

Factors resulting in hypercoagulability Hypercoagulability Hypercoagulable States:

• Hereditary thrombophilia Thrombophilia A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. Hypercoagulable States, most often:
  • Factor V Leiden Factor V Leiden Hypercoagulable States
  • 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 or S deficiency
  • Antithrombin deficiency Antithrombin deficiency An absence or reduced level of antithrombin III leading to an increased risk for thrombosis. Budd-Chiari Syndrome
• 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/ oral contraceptive Oral contraceptive Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Benign Liver Tumors pill ( OCP OCP Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Benign Liver Tumors) use: 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 increases the production of clotting factors in the 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.
• Cancer
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases: Oxidant gases and other chemicals in cigarette smoke produce free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage which lead to platelet aggregation Platelet aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Hemostasis and an increase in the production of procoagulant molecules.
• Heparin-induced thrombocytopenia Heparin-Induced Thrombocytopenia Thrombocytopenia (HIT)

Other risk factors and/or conditions affecting multiple components of the Virchow triad:

• Prior 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/ 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: 30 times increased risk of recurrent 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/PE
• Family history Family History Adult Health Maintenance
• Age > 60 years
• 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
• Autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency:
  • 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
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus)
  • Inflammatory bowel disease
• Chemotherapy Chemotherapy Osteosarcoma

Mnemonic

To remember 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 risk factors, think THROMBOSIS Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus.

• Travel
• Hypercoagulable/Hormone replacement therapy ( HRT HRT 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)
• Recreational drugs
• Old (age > 60)
• Malignancy
• Blood disorders
• Obesity/Obstetrics
• Surgery/Smoking
• Immobilization
• Sickness ( 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) [HF]/ 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 [ MI MI 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], inflammatory bowel disease [IBD], 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, vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus)

Pathophysiology

Site of origin^[4,5]

• 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 begins at the site of endothelial damage, often near the venous valves.
• Clots usually begin in the deep vessels of the calf and extend proximally into the larger veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology.
• Veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology affected the most:
  • Popliteal, femoral, and iliac veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
  • During 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: pelvic veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology

Composition of thrombus^[4,5]

• Red blood cells Red blood cells Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology
• Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
• Fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis

Three pathophysiologic mechanisms (Virchow’s triad)^[1,4,5]

1. Blood hypercoagulability Hypercoagulability Hypercoagulable States:
   • Increased clotting factor synthesis Synthesis Polymerase Chain Reaction (PCR) 
   • Increased platelet activation Platelet activation A series of progressive, overlapping events, triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. Hemostasis and adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies
   • Decreased 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
2. Endothelial damage: 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/trauma →
   • Exposure of von Willebrand factor von Willebrand factor A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in von Willebrand diseases is due to the deficiency of this factor. Hemostasis (vWF) → results in platelet activation Platelet activation A series of progressive, overlapping events, triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. Hemostasis and formation of the platelet plug Platelet plug Hemostasis
   • Exposure of tissue factor → activates the extrinsic pathway Extrinsic pathway The extrinsic pathway is the primary physiological mechanism by which clotting is initiated Hemostasis in the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis → results in fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis clot formation
3. Abnormal 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/stasis: immobilization Immobilization Delirium, venous valve incompetence → stasis of blood → more time for clot formation

Complications 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^[3,4]

• 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:
  • A condition in which 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 is obstructed by a portion of thrombus that has broken off of a 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 traveled to the lung
  • Potentially fatal
  • Has both cardiovascular and respiratory effects ( 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 hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage)
• Post-thrombotic syndrome Post-thrombotic syndrome A condition caused by one or more episodes of deep vein thrombosis, usually the blood clots are lodged in the legs. Clinical features include edema; pain; aching; heaviness; and muscle cramp in the leg. When severe leg swelling leads to skin breakdown, it is called venous stasis ulcer. Deep Vein Thrombosis (most common complication of proximal 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)
  • Symptoms include pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and swelling Swelling Inflammation.
  • Chronic venous insufficiency Chronic venous insufficiency Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. “Chronic venous insufficiency” refers to the more severe forms of chronic venous disease. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease. Chronic Venous Insufficiency: Venous wall and valve dysfunction can occur as a result of fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans due to 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 around the thrombus.
  • Ulcers develop on lower extremities.
  • Mobility can be reduced.
  • Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experience paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome.
  • Occurs in 25%–50% of all 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

Clinical Presentation

• A majority of cases are asymptomatic.^[2,4,5]
• Symptoms/manifestations are usually unilateral.
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Warmth
  • 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
  • Intact distal pulses
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever (due to cytokine release)
  • Palpable cords representing the thrombotic vein (rare but significant finding)
  • Homan sign Homan sign 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 on dorsiflexion of the foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy (neither sensitive nor specific)
  • The 1st manifestation can be 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 (which presents with chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, 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)
  • Chronic 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 can be asymptomatic and cause chronic venous insufficiency Chronic venous insufficiency Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. “Chronic venous insufficiency” refers to the more severe forms of chronic venous disease. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease. Chronic Venous Insufficiency.
• Phlegmasia alba dolens (“painful white inflammation”):
  • Occurs with a massive occlusion of the major deep vessels, but with patent collateral vessels and without 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
  • Presents with 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, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and blanching Blanching Dermatologic Examination without cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination
  • Can progress to phlegmasia cerulea dolens Phlegmasia cerulea dolens Near-total occlusion of the deep venous system resulting in venous gangrene. Acute Limb Ischemia and compartment syndrome Compartment Syndrome Compartment syndrome is a surgical emergency usually occurring secondary to trauma. The condition is marked by increased pressure within a compartment that compromises the circulation and function of the tissues within that space. Compartment Syndrome 
• Phlegmasia cerulea dolens Phlegmasia cerulea dolens Near-total occlusion of the deep venous system resulting in venous gangrene. Acute Limb Ischemia (“ painful blue inflammation Painful blue inflammation Near-total occlusion of the deep venous system resulting in venous gangrene. Acute Limb Ischemia”):
  • Obstruction of all veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology of an extremity → severe venous congestion → limited arterial 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 → 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 → tissue death
  • Presents with 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, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, pulselessness Pulselessness Cardiac Arrest, and cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination

Diagnosis

The following is based on US medical society guidelines.

• Details of the recommendations of the American Society of Hematology
• Diagnostic approach based on UK recommendations

First test, depending on degree of suspicion^[2,9‒11]

• Wells criteria are used to assess risk of a 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 based on the presentation of the individual (see table):
  • 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: 0
  • Moderate 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: 1 to 2 points
  • 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 to 8 points
• Modified Wells criteria: 
  • Adds a clinical feature (previously documented 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) which is given a score of 1.
  • Given this modification, the 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 is either likely or unlikely based on the scoring.
    • 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 likely: ≥ 2
    • 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 unlikely: < 2
• If the suspicion 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 is high ( Wells score Wells score Deep Vein Thrombosis ≥ 2), the test of choice is ultrasonography with 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). Diagnostic imaging findings include:
  • Lumen is noncompressible
  • Hyperechoic Hyperechoic A structure that produces a high-amplitude echo (lighter grays and white) Ultrasound (Sonography) mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
  • Decreased/absent 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
• If the suspicion 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 is low ( Wells score Wells score Deep Vein Thrombosis < 2), the first test should be D-dimer D-dimer Deep Vein Thrombosis.
  • High sensitivity but low specificity
  • D-dimer D-dimer Deep Vein Thrombosis should not be obtained if it is expected to be positive (e.g., recent surgery).
  • Negative test (normal/low D-dimer D-dimer Deep Vein Thrombosis levels) rules out 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
  • Positive test (elevated D-dimer D-dimer Deep Vein Thrombosis levels) warrants ultrasonography for confirmation
• Wells criteria calculator

Further tests^[2,9,11]

• Baseline laboratory studies to obtain:
  • CBC (assess hemoglobin and platelet count)
  • Chemistries (assess renal and 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 function)
  • Coagulation panel (PT/INR, aPTT)
• Age-appropriate cancer screening Screening Preoperative Care (e.g., digital rectal exam [ DRE DRE A physical examination in which the qualified health care worker inserts a lubricated, gloved finger of one hand into the rectum and may use the other hand to press on the lower abdomen or pelvic area to palpate for abnormalities in the lower rectum, and nearby organs or tissues. The method is commonly used to check the lower rectum, the prostate gland in men, and the uterus and ovaries in women. Prostate Cancer Screening], mammography Mammography Radiographic examination of the breast. Breast Cancer Screening, colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening)
• Hypercoagulability Hypercoagulability Hypercoagulable States studies are indicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with:
  • Family history Family History Adult Health Maintenance of coagulation disorders
  • Young age
  • Unusual localization of thrombus
  • Recurrence 
• Hemodynamically stable individuals with a 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 signs of PE (e.g., chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, 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): contrast-enhanced CT scan of the chest 
• Hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma with a 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 signs of PE: bedside echocardiogram Echocardiogram Transposition of the Great Vessels to visualize right ventricular dilation
• Venography Venography Budd-Chiari Syndrome:
  • Previously the gold standard
  • Dye is injected into a dorsal foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy vein and images are taken to look for obstructing thrombi.
  • Invasive and rarely done anymore
• Contrast-enhanced computed tomographic venography Venography Budd-Chiari Syndrome (CTV) or magnetic resonance venography Venography Budd-Chiari Syndrome (MRV)
  • Alternative imaging options if US is inconclusive
  • More costly with risk of contrast exposure and radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma (in CTV)
  • Thrombus seen as an intraluminal filling defect

Management

Anticoagulation Anticoagulation Pulmonary Hypertension Drugs is the mainstay of therapy for DVTs. Depending on the situation, some individuals may require thrombolysis, an invasive procedure, and/or lifelong anticoagulation Anticoagulation Pulmonary Hypertension Drugs. The following is based on US and UK recommendations, but management may vary based on location.

Initial treatment considerations

Setting^{[6, 7]}:

• Outpatient treatment is appropriate for acute, uncomplicated 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.
• Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium is indicated for:
  • Limb-threatening 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
  • Bleeding risk
  • Poor social support
  • Inability to afford or administer medications reliably
  • Inability to return to the hospital if clinical deterioration occurs

Proximal vs distal 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^[8]:

• Proximal 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:
  • Thrombus in the popliteal, femoral, or iliac veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
  • Anticoagulation Anticoagulation Pulmonary Hypertension Drugs is indicated.
• Distal 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:
  • Thrombus below the knee
  • Carries lower risk of embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding
  • Anticoagulation Anticoagulation Pulmonary Hypertension Drugs is recommended for symptomatic distal 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.
  • Anticoagulation Anticoagulation Pulmonary Hypertension Drugs is recommended for asymptomatic distal 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 but with risk factors for extension Extension Examination of the Upper Limbs:
    • Elevated D-dimer D-dimer Deep Vein Thrombosis
    • Unprovoked 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
    • Large thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus (> 5 cm length, > 7 mm in diameter)
    • Multiple veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology involved
    • Persistent risk factors (e.g., cancer)
    • Prior history 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 or PE
    • Inpatient status
    • Limited mobility
    • COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems).
  • Serial US (once a week for 2 weeks) is an option for an isolated 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 with low risk of extension Extension Examination of the Upper Limbs or with high risk of bleeding.
    • If clot resolves, there is no need for anticoagulation Anticoagulation Pulmonary Hypertension Drugs.
    • If clot extends towards the proximal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology, start anticoagulation Anticoagulation Pulmonary Hypertension Drugs.
    • If clot is stable or extension Extension Examination of the Upper Limbs is limited to distal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology, consider anticoagulation Anticoagulation Pulmonary Hypertension Drugs.

Anticoagulation Anticoagulation Pulmonary Hypertension Drugs

Anticoagulation Anticoagulation Pulmonary Hypertension Drugs recommendations vary slightly depending on location. For UK recommendations, click here.

US anticoagulation Anticoagulation Pulmonary Hypertension Drugs guidelines:^{[6, 8]}

• Options:
  • Low molecular weight heparin (LMWH)
    • 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 every 12 hours or 1.5 mg/kg 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)
    • Follow hospital protocol
  • 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
    • < 50 kg: 5 mg daily
    • 50–100 kg: 7.5 mg daily
    • > 100 kg: 10 mg daily
  • 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
    • 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 2 times daily (with food) for 21 days, followed by 20 mg daily (with food)
    • Apixaban Apixaban Anticoagulants: 10 mg 2 times daily for 7 days, followed by 5 mg 2 times daily
  • 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
    • Can be administered after 5–10 days of initial treatment with LMWH or 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
    • 150 mg 2 times daily
• 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. DOACs DOACs Anticoagulants are currently preferred as first-line therapy for most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, except:
  • Severe renal insufficiency
  • Moderate-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
  • Antiphospholipid antibody syndrome
• 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
• Notes:
  • 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 due to the brief period of hypercoagulability Hypercoagulability Hypercoagulable States that occurs when starting it.
  • 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 is preferred in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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.

UK anticoagulation Anticoagulation Pulmonary Hypertension Drugs guidelines:^[9]

• Duration of anticoagulation Anticoagulation Pulmonary Hypertension Drugs:
  • 3 months:
    • Consider discontinuation if provoking factor is no longer present
    • When anticoagulation Anticoagulation Pulmonary Hypertension Drugs is stopped, education about recurrence is given to the individual.
  • Longer anticoagulation Anticoagulation Pulmonary Hypertension Drugs:
    • > 3 months for unprovoked 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 (3–6 months for active malignancy Malignancy Hemothorax)
    • Then, reassess the risks and benefits of continuing, changing, or discontinuing anticoagulation Anticoagulation Pulmonary Hypertension Drugs
• Options:
  • For individuals without malignancy Malignancy Hemothorax, renal impairment, 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, or hemodynamic instability:
    • 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
    • LMWH, either:
      • 5-day course, followed by 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
      • 5-day bridge with 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, followed by 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 monotherapy to maintain INR ≥ 2.0
  • For individuals with an active malignancy Malignancy Hemothorax, options include:
    • Direct factor Xa inhibitors or direct thrombin Thrombin An enzyme formed from prothrombin that converts fibrinogen to fibrin. Hemostasis inhibitors
    • LMWH
    • LMWH bridge to 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
  • For individuals with renal impairment:
    • If creatinine clearance Creatinine clearance Kidney Function Tests (CrCl) is 15–50 mL/min:
      • Apixaban Apixaban Anticoagulants or 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
      • LMWH for 5 days, followed by 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 (if CrCl ≥ 30 mL/min)
      • LMWH bridge to 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
  • For individuals with 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: LMWH bridge to 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

Secondary prevention 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^[6]

• Administered for 3‒6 months to prevent recurrence (some individuals may require lifelong therapy)
• Duration of therapy depends on risk factors for recurrence and bleeding (risk calculator).
  • Anticoagulation Anticoagulation Pulmonary Hypertension Drugs for a minimum of 3 months
  • Longer or indefinite therapy is suggested for:
    • Unprovoked 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
    • 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 associated with a chronic or persistent risk factor
• 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:
    • Often used in individuals 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).

Other management options^{[6, 8]}

• Thrombolysis:
  • Medications that cause thrombolysis (as opposed to simply preventing further coagulation and letting natural thrombolytic processes occur)
  • Primary drug: 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)
  • Catheter-directed therapy is generally preferred over systemic thrombolysis.
  • Indications for thrombolysis:
    • Large proximal 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/or phlegmasia cerulea dolens Phlegmasia cerulea dolens Near-total occlusion of the deep venous system resulting in venous gangrene. Acute Limb Ischemia (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 causing occlusion of venous 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)
    • 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 with hemodynamic instability (systolic blood pressure < 90)
    • Refractory to anticoagulation Anticoagulation Pulmonary Hypertension Drugs
• Thrombectomy Thrombectomy Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. Vascular Surgery:
  • Surgical removal of a thrombus
  • Indications for thrombectomy Thrombectomy Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. Vascular Surgery:
    • Phlegmasia cerulea dolens Phlegmasia cerulea dolens Near-total occlusion of the deep venous system resulting in venous gangrene. Acute Limb Ischemia
    • Large thrombus refractory to fibrinolysis
    • Large thrombus + 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/ thrombolytics Thrombolytics Thrombolytics, also known as fibrinolytics, include recombinant tissue plasminogen activator (TPa) (i.e., alteplase, reteplase, and tenecteplase), urokinase, and streptokinase. The agents promote the breakdown of a blood clot by converting plasminogen to plasmin, which then degrades fibrin. Thrombolytics
• 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 of a filter in 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 catch any thrombotic emboli that may break off from the 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 an effort to prevent PE
  • Indications for an 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
    • 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/ thrombolytics Thrombolytics Thrombolytics, also known as fibrinolytics, include recombinant tissue plasminogen activator (TPa) (i.e., alteplase, reteplase, and tenecteplase), urokinase, and streptokinase. The agents promote the breakdown of a blood clot by converting plasminogen to plasmin, which then degrades fibrin. Thrombolytics/ thrombectomy Thrombectomy Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. Vascular Surgery (e.g., major bleeding)
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have 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 PE while on appropriate anticoagulation Anticoagulation Pulmonary Hypertension Drugs
  • It is not recommended to use an 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 in addition to anticoagulation Anticoagulation Pulmonary Hypertension Drugs.
• Treatment of phlegmasia cerulea dolens Phlegmasia cerulea dolens Near-total occlusion of the deep venous system resulting in venous gangrene. Acute Limb Ischemia:
  • Initiation of adequate anticoagulation Anticoagulation Pulmonary Hypertension Drugs
  • Thrombectomy Thrombectomy Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. Vascular Surgery
  • Fasciotomy Fasciotomy Surgical incision on the fascia. It is used to decompress compartment pressure (e.g. in compartment syndromes; circumferential burns and extremity injuries) or to release contractures (e.g. in dupuytren’s contracture). Compartment Syndrome if compartment syndrome Compartment Syndrome Compartment syndrome is a surgical emergency usually occurring secondary to trauma. The condition is marked by increased pressure within a compartment that compromises the circulation and function of the tissues within that space. Compartment Syndrome present
  • Fibrinolysis if thrombectomy Thrombectomy Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. Vascular Surgery fails
  • Amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation: if both thrombectomy Thrombectomy Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. Vascular Surgery and fibrinolysis fail, leading to critical limb 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 and limb loss

Prophylaxis Prophylaxis Cephalosporins

• Early mobilization after surgery 
• Postoperative prophylactic anticoagulation Anticoagulation Pulmonary Hypertension Drugs
• 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 (OCPs)) 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

Differential Diagnosis

The following conditions can present similarly to 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:

• Peripheral vascular disease: a chronic disease involving 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 in the extremities, and the main cause of intermittent claudication Intermittent claudication A symptom complex characterized by pain and weakness in skeletal muscle group associated with exercise, such as leg pain and weakness brought on by walking. Such muscle limpness disappears after a brief rest and is often relates to arterial stenosis; muscle ischemia; and accumulation of lactate. Thromboangiitis Obliterans (Buerger’s Disease). The chronic atherosclerotic process leads to arterial stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) and, at a later stage, to the complete occlusion of the 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 (either from embolism or thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus).
• Baker cyst: a synovial swelling Swelling Inflammation in the popliteal space (space behind the knee). The pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways worsens if the patient fully flexes or extends the knee. Baker cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are commonly associated with rheumatoid or osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis. A ruptured Baker cyst can mimic an acute 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.
• Lymphedema Lymphedema Edema due to obstruction of lymph vessels or disorders of the lymph nodes. Lymphatic Filariasis (Elephantiasis): localized fluid retention and tissue swelling Swelling Inflammation caused by a compromised lymphatic system Lymphatic system A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs. Lymphedema Lymphedema Edema due to obstruction of lymph vessels or disorders of the lymph nodes. Lymphatic Filariasis (Elephantiasis) can be caused by surgery, parasitic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, or hereditary conditions. The condition is often bilateral, unlike a 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, which is unilateral. Additionally, a D-dimer D-dimer Deep Vein Thrombosis may be negative with lymphedema Lymphedema Edema due to obstruction of lymph vessels or disorders of the lymph nodes. Lymphatic Filariasis (Elephantiasis), but is almost always positive when a 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 is present.
• Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis: an infection of the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions and subcutaneous fat Subcutaneous fat Fatty tissue under the skin throughout the body. Erythema Nodosum. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with localized swelling Swelling Inflammation, warmth, redness Redness Inflammation, and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in an area. An abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease may form. A D-dimer D-dimer Deep Vein Thrombosis may be negative, and ultrasound will fail to show a 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.