Deep Venous Thrombosis (DVT)


Risk Factors for Venous Thromboembolism

General Comments

  • Risk Factors are the Same for Both Deep Venous Thrombosis (DVT) and Acute Pulmonary Embolism (PE) (see Deep Venous Thrombosis and Acute Pulmonary Embolism)
    • Risk Factor Can Be Identified in >80% of Patients with Venous Thrombosis
      • More than One Factor May Often Be Present
      • 50% of Thrombotic Events in Patients with Inherited Hypercoagulable States are Associated with an Additional Risk Factor (Pregnancy, Surgery, Prolonged Immobilization, Oral Contraceptives)

Inherited Hypercoagulable States (see Hypercoagulable States)

  • General Comments
    • Factor V Leiden Gene Mutation and Prothrombin Gene Mutation Account for 50-60% of Inherited (Primary) Hypercoagulable States
  • Antithrombin Deficiency (see Antithrombin Deficiency)
  • Dysfibrinogenemia (see Dysfibrinogenemia)
    • Epidemiology
      • Rare
  • Factor V Leiden (see Factor V Leiden)
    • Epidemiology
      • Factor V Leiden is the Most Common Inherited Hypercoagulable State in Caucasian Populations
    • Diagnosis
      • Abnormal Activated Protein C (APC) Resistance Assay
  • Factor XII Deficiency (see Factor XII Deficiency)
    • Epidemiology
      • Rare
  • Family History of Venous Thromboembolism
    • Epidemiology
      • Strong Risk Factor
  • Heparin Cofactor II Deficiency
    • Epidemiology
      • Unclear Risk Factor for Venous Thromboembolism
      • Rare
  • Hereditary Hemorrhagic Telangiectasia (HHT) (Osler-Weber-Rendu Syndrome) (see Hereditary Hemorrhagic Telangiectasia)
    • Epidemiology
      • Associated with Decreased Serum Iron Levels and Increased Plasma Factor VIII Levels (Thorax, 2012) [MEDLINE]
    • Physiology
      • Associated with Decreased Serum Iron Levels (Due to Inadequate Replacement of Hemorrhagic Iron Loss) and Increased Plasma Factor VIII Levels (Thorax, 2012) [MEDLINE]
  • Homocystinuria
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Increased Factor VIII Coagulant Activity
    • Epidemiology
      • Rare
  • Plasminogen Deficiency
    • Epidemiology
      • Unclear Risk Factor for Venous Thromboembolism
  • Protein C Deficiency (see Protein C Deficiency)
  • Protein S Deficiency (see Protein S Deficiency)
  • Prothrombin G20210A Gene Mutation (see Prothrombin G20210A Gene Mutation)
    • Epidemiology
      • Second Most Common Inherited Hypercoagulable State (After Factor V Leiden)
    • Diagnosis
      • Abnormal Activated Protein C (APC) Resistance Assay
  • Race/Ethnicity
    • Epidemiology
      • Data from the California Patient Discharge Dataset Indicate that Race/Ethnicity are Associated with the Risk of Venous Thromboembolism (Thromb Res, 2009) [MEDLINE]
        • Asians/Pacific Islanders and Hispanics Have a Lower Incidence of Venous Thromboembolism, as Compared to Non-Hispanic Whites
        • Blacks/African Americans Have a Higher Incidence of Venous Thromboembolism of Venous Thromboembolism, as Compared to Non-Hispanic Whites
      • Multivariable Cox Proportional Hazards Regression Model Study of the Relationship Between Race/Ethnicity and Risk of Cancer-Associated Thrombosis (Data from the California Cancer Registry) (Blood Adv, 2022) [MEDLINE]: n = 942, 109 (with the 13 Most Common, First Primary Malignancies)
        • Blacks/African Americans Had a Higher Incidence of Cancer-Associated Thrombosis for All Tumor Types (Except Multiple Myeloma), as Compared with Non-Hispanic Whites, After Adjusting for Potential Confounders
        • Asians/Pacific Islanders Had a Lower Incidence of Cancer-Associated Thrombosis, as Compared with Non-Hispanic Whites, After Adjusting for Potential Confounders
        • The Main Driver for the Racial/Ethnic Differences was the Incidence of Acute Pulmonary Embolism
        • Authors Speculated the Association of Race/Ethnicity with Incidence of Cancer-Associated Thrombosis May Be Partially Because of Underlying Thrombotic Predisposition Which Varies by Ancestry, But They Also Considered the Potential Impact of Social Determinants of Health Which Might Impact the Findings

Acquired Hypercoagulable States (see Hypercoagulable States)

Cardiovascular Disease

  • Acute Myocardial Infarction (Within Prior 3 Months) (see Coronary Artery Disease)
    • Epidemiology
      • Myocardial Infarction (in Prior 3 Months) is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]
  • Atrial Fibrillation/Flutter (see Atrial Fibrillation and Atrial Flutter)
    • Epidemiology
      • Hospitalization for Atrial Fibrillation/Flutter (within Prior 3 Months) is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]
  • Congestive Heart Failure (CHF) (see Congestive Heart Failure)
    • Epidemiology
      • Congestive Heart Failure Itself is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
      • Hospitalization for Congestive Heart Failure (within Prior 3 Months) is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]
  • Hypertension (see Hypertension)
    • Epidemiology
      • Longitudinal Investigation of Thromboembolism Etiology (LITE) Study Indicated that Alcohol Use, Hypertension, Hyperlipidemia, Physical Inactivity, and Tobacco Abuse were Not Associated with an Increased Risk of Venous Thromboembolism (Arch Intern Med, 2002) [MEDLINE]
      • Meta-Analysis Indicated that Obesity (Risk 2.33), Hypertension (Risk 1.51), Diabetes Mellitus (Risk 1.42), Smoking (Risk 1.15), and Hypercholesterolemia (Risk 1.16) Increased the Risk of Venous Thromboembolism (Circulation, 2008) [MEDLINE]
      • Hypertension is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]

Central Venous Catheter/Lead/Device

  • Central Venous Catheter (CVC) (see Central Venous Catheter)
    • Epidemiology
      • Central Venous Catheters/Leads are a Moderate Risk for Venous Thromboembolism (Odds Ratio 2-9) (Eur Heart J, 2020) [MEDLINE]
  • Peripherally Inserted Central Catheter (PICC) (see Peripherally Inserted Central Catheter)
    • Epidemiology
      • Meta-Analysis Comparing PICC Line with Central Venous Catheter (Lancet, 2013) [MEDLINE]
        • PICC Lines Had a Higher Risk of Venous Thrombosis than Central Venous Catheters, Especially in Patients Who are Critically Ill or in Those with Cancer
        • PICC Lines Had No Increased Risk of Acute Pulmonary Embolism

Chronic Myeloproliferative Disease (see Chronic Myeloproliferative Diseases)

  • Essential Thrombocythemia (see Essential Thrombocythemia)
    • Diagnosis
      • Some Cases Manifest Abnormal Activated Protein C (APC) Resistance Assay
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Polycythemia Vera (see Polycythemia Vera)
    • Epidemiology
      • Venous Thrombosis Occurs in 7% of Polycythemia Vera Cases (Leukemia, 2013) [MEDLINE]
    • Physiology
      • Hyperviscosity and Qualitative Platelet Defects
    • Diagnosis
      • Some Cases Manifest Abnormal Activated Protein C (APC) Resistance Assay
    • Clinical
      • May Result in Both Venous and Arterial Thromboses

Endocrinologic Therapy/Disease

  • Diabetes Mellitus (DM) (see Diabetes Mellitus)
    • Epidemiology
      • Longitudinal Investigation of Thromboembolism Etiology (LITE) Study Demonstrated that Diabetes Mellitus Increased the Risk of Venous Thromboembolism (Adjusted Hazard Ratio 1.5) (Arch Intern Med, 2002) [MEDLINE]
      • Meta-Analysis Indicated that Obesity (Risk 2.33), Hypertension (Risk 1.51), Diabetes Mellitus (Risk 1.42), Smoking (Risk 1.15), and Hypercholesterolemia (Risk 1.16) Increased the Risk of Venous Thromboembolism (Circulation, 2008) [MEDLINE]
      • Diabetes Mellitus is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]
  • Hormonal Therapy: see Drug/Toxin below
  • In Vitro Fertilization
    • Epidemiology
      • In Vitro Fertilization is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
  • Ovarian Hyperstimulation Syndrome (see Ovarian Hyperstimulation Syndrome)
    • Physiology
      • Due to Capillary Leak Syndrome with Hemoconcentration
  • Polycystic Ovary Syndrome (see Polycystic Ovary Syndrome)
  • Pregnancy (see Pregnancy)
    • Epidemiology
      • Pregnancy Itself is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]
      • Postpartum Period is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
      • Incidence of Deep Venous Thrombosis is Roughly Equal Throughout Pregnancy
        • First Trimester: 22%
        • Second Trimester: 41%
        • Third Trimester: 37%
      • Incidence of Acute Pulmonary Embolism During Pregnancy
        • Prepartum: 34%
        • Postpartum: 66% (with 82% of these occurring following C-section)
      • Physiology
        • Increased Risk of Deep Venous Thrombosis in Left Leg During Pregnancy (Possibly Due to Left Common Iliac Vein Compression by the Overlying Right Iliac Artery)
    • Diagnosis
      • Some Cases Manifest Abnormal Activated Protein C (APC) Resistance Assay
    • Treatment
      • Aspirin Does Not Affect the Risk of Deep Venous Thrombosis in Pregnancy (Even in the Presence of Antiphospholipid Antibody Syndrome)

Gastrointestinal/Hepatic Disease

  • Inflammatory Bowel Disease (see Inflammatory Bowel Disease)
    • General Comments
      • Inflammatory Bowel Disease is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
    • Crohn’s Disease (see Crohn’s Disease)
    • Ulcerative Colitis (UC) (see Ulcerative Colitis)
  • Liver Disease (see Cirrhosis)
    • Epidemiology
      • There is a High (6.3%) Risk of Venous Thromboembolism in Hospitalized Liver Disease Patients, Despite Abnormal Coagulation Parameters (Chest, 2010) [MEDLINE]

Hyperviscosity Syndrome

Immobilization

  • Bedrest
    • Epidemiology
      • Bedrest >3 Days is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]
  • Critical Illness (Especially with Mechanical Ventilation)
    • Epidemiology
      • Risk of Deep Venous Thrombosis in Mechanically-Ventilated Patients is 5-10%, Despite Adequate DVT Prophylaxis (J Intensive Care Med, 2006) [MEDLINE] (Crit Care MED, 2005) [MEDLINE] (NEJM, 2011) [MEDLINE]
  • Extended Travel (“Travelers’ Thrombosis”)
    • Epidemiology
      • Travel (Air, Train, Auto) for >4 hrs is Associated with Increased Risk of Deep Venous Thrombosis (Aviat Space Environ Med, 2014) [MEDLINE]
      • Incidence of Pulmonary Embolism Following Air Travel is Correlated with the Distance Traveled (NEJM, 2001) [MEDLINE]
      • Extended Travel is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]
  • Lower Extremity Fracture/Injury
    • Epidemiology
      • Lower Extremity Fracture is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]

Infection

  • General Comments
    • Infection (Particularly Pneumonia, Urinary Tract Infection, and Human Immunodeficiency Virus Infection) is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus)
  • Sepsis (see Sepsis)
    • Epidemiology
      • Multicenter Prospective Study of Risk Factors for and Incidence of Venous Thromboembolism in Severe Sepsis/Septic Shock (Chest, 2015) [MEDLINE]
        • Despite Guideline-Recommended DVT Prophylaxis, the Incidence of Venous Thromboembolism was 37.2% in Patients with Severe Sepsis/Septic Shock
        • Most Venous Thromboembolism Events were Clinically Significant (Defined as Pulmonary Embolism, Proximal DVT, and/or Symptomatic Distal DVT) and were Associated with an Increased Length of Stay (18.2 ± 9.9 days vs 13.4 ± 11.5 days, P < 0.05)
        • Mortality was Higher in Patients with Acute Venous Thromboembolism, But this Did Not Reach Statistical Significance
        • Insertion of a CVC and Longer Mechanical Ventilation Duration were Significant Venous Thromboembolism Risk Factors
        • There was No Difference in the Incidence of Venous Thromboembolism Incidence Between Patients Receiving Pharmacologic Prophylaxis vs Sequential Compression Devices (37.3% vs 36.3%)
        • There was No Difference in the Incidence of Venous Thromboembolism Incidence Between Patients Receiving Low Molecular Weight Heparin Prophylaxis vs Unfractionated Heparin Prophylaxis (33.3% vs 41.3%)
  • Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) (see Severe Acute Respiratory Syndrome Coronavirus-2)
    • Epidemiology
      • In a Multicenter Prospective Cohort Study of Patients with Acute Respiratory Distress Syndrome (ARDS), Patients with SARS CoV-2-Associated ARDS Had a Significantly Higher Incidence of Acute Pulmonary Embolism, as Compared to Non-SARS CoV-2-Associated ARDS (11.7% vs 2.1%, p < 0.008) (Intensive Care Med, 2020) [MEDLINE]
      • High Relative Incidence of Vascular Thrombotic Events Soon After SARS CoV-2 Diagnosis Declines More Rapidly for Arterial Thromboses than for Venous Thromboembolism (Circulation, 2022) [MEDLINE]
        • However, Incidence of Vascular Thrombotic Events Remains Elevated Up to 49 wks After SARS CoV-2 Diagnosis
  • Tuberculosis (Active) (see Tuberculosis)
    • Epidemiology
      • There May Be an Association Between Tuberculosis and Venous Thromboembolism (Asian Cardiovasc Thorac Ann, 2014) [MEDLINE]
  • Varicella-Zoster Virus (VZV) (see Varicella-Zoster Virus)
    • Epidemiology
      • Varicella-Zoster Virus Infection-Associated Stroke and Deep Venous Thrombosis Have Been Rarely Reported in Children (Pediatr Infect Dis J, 2015) [MEDLINE]

Malignancy

  • General Comments
    • Malignancy Imparts a 4 to 7-Fold Increased Risk of Developing Venous Thromboembolism, as Compared to the General Population (Med Insights Oncol, 2014) [MEDLINE]
    • Cancer (Particularly Metastatic Cancer) is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
    • Incidence of Cancer-Associated Thrombosis Varies by Tumor Type, Stage at Diagnosis, Type of Therapy, and Patient Comorbidities (Blood Adv, 2022) [MEDLINE]
    • Risk of Venous Thrombembolism in Course of Cancer is Highest During the Initial Hospitalization, at the Onset of Chemotherapy, and at the Time of Disease Progression
    • Presence of a Central Venous Catheter Further Compounds the Risk of Malignancy-Associated Venous Thromboembolism
    • Most Cancers (78%) are Diagnosed Before the Diagnosis of the Deep Venous Thrombosis
  • Common Sites of Malignancies at Time of Venous Thromboembolism Diagnosis
    • Lung Cancer (see Lung Cancer): 17% of cases develop venous thromboembolism
    • Pancreatic Cancer (see Pancreatic Cancer): 10% of cases develop venous thromboembolism
    • Colorectal Cancer (see Colorectal Cancer): 8% of cases develop venous thromboembolism
    • Renal Cancer (Renal Cancer): 8% of cases develop venous thromboembolism
    • Prostate Cancer (Prostate Cancer): 7% of cases develop venous thromboembolism

Neurologic Disease

  • Ischemic Cerebrovascular Accident (CVA) (Within Prior 3 Months) (see Ischemic Cerebrovascular Accident)
    • Epidemiology
      • Stroke with Paralysis is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]

Obesity (see Obesity)

  • Epidemiology
    • Longitudinal Investigation of Thromboembolism Etiology (LITE) Study Demonstrated that Obesity Increased the Risk of Venous Thromboembolism Using Age/Race/Sex-Adjusted Hazard Ratios for BMI (BMI <25 = 1.0, BMI 25-30 = 1.5, BMI 30-35 = 2.2, BMI 35-40 = 1.5, and BMI ≥40 = 2.7) (Arch Intern Med, 2002) [MEDLINE]
    • Meta-Analysis Indicated that Obesity (Risk 2.33), Hypertension (Risk 1.51), Diabetes Mellitus (Risk 1.42), Smoking (Risk 1.15), and Hypercholesterolemia (Risk 1.16) Increased the Risk of Venous Thromboembolism (Circulation, 2008) [MEDLINE]
    • Obesity Increased the Risk of Pulmonary Embolism (Relative Risk 2.03), But Decreased the Mortality of Pulmonary Embolism in Hospitalized Patients (Thromb Res, 2011) [MEDLINE]
    • Obesity is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]

Renal Disease

Rheumatologic Disease/Autoimmune Disease/Vasculitis (see Vasculitis)

  • General Comments
    • Autoimmune Disease is a Moderate Risk for Venous Thromboembolism (Odds Ratio 2-9) (Eur Heart J, 2020) [MEDLINE]
  • Behcet’s Disease (see Behcet’s Disease)
    • Clinical
      • Arterial/Venous Thrombosis May Occur in Behcet’s Disease (Clin Exp Rheumatol, 2018) [MEDLINE]
  • Eosinophilic Granulomatosis with Polyangiitis (EGPA) (Churg-Strauss Syndrome) (see Eosinophilic Granulomatosis with Polyangiitis)
  • Giant Cell Arteritis (Temporal Arteritis, Horton Disease, Cranial Arteritis) (see Giant Cell Arteritis)
    • Epidemiology
      • Incidence of Venous Thromboembolism (DVT or PE) was 13.3 per 1000 Person-Years with Incidence Rate Ratio of 3.58 (2.33-5.34, CI 95%) (Ann Rheum Dis, 2016) [MEDLINE]
  • Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) (see Granulomatosis with Polyangiitis)
  • Microscopic Polyangiitis (see Microscopic Polyangiitis)
  • Psoriasis (Chronic) (see Psoriasis)
  • Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis)
  • Scleroderma (see Scleroderma)
    • Epidemiology
      • Scleroderma Increases the Risk of Venous Thromboembolism (Rheumatology-Oxford, 2014) [MEDLINE] (Arthritis Care Res-Hoboken, 2016) [MEDLINE]
      • Increased Risk Appears to Be the Highest in the First Year After the Diagnosis of Scleroderma
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
    • Physiology
      • Hypercoagulability is Believed to Be Related to Impaired Fibrinolysis (Semin Thromb Hemost, 2013) [MEDLINE]

Surgery

  • Cancer Surgery
  • Laparoscopic Surgery
    • Epidemiology
      • Laparoscopic Surgery is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]
  • Major Vascular Surgery
  • Neurosurgery
  • Orthopedic Surgery
    • Arthroscopic Knee Surgery
      • Arthroscopic Knee Surgery is a Moderate Risk for Venous Thromboembolism (Odds Ratio 2-9) (Eur Heart J, 2020) [MEDLINE]
    • Total Hip Arthroplasty (see Total Hip Arthroplasty)
      • 30-day Risk of Symptomatic Non-Fatal Venous Thromboembolism is 2.5% (NEJM, 2000) [MEDLINE] (Lancet, 2001) [MEDLINE]
      • Total Hip Replacement is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]
    • Total Knee Arthroplasty (see Total Knee Arthroplasty)
      • 30-Day Risk of Symptomatic Non-Fatal Venous Thromboembolism is 1.4% (NEJM, 2000) [MEDLINE] (Lancet, 20001) [MEDLINE]
      • Total Knee Replacement is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]

Trauma

  • Spinal Cord Injury (SCI) (see Spinal Cord Injury)
    • Epidemiology
      • Spinal Cord Injury is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]
  • Trauma of Any Etiology
    • Epidemiology
      • Major Trauma is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]
    • Physiology
      • Decreased Lower Extremity Venous Blood Flow, Decreased Fibrinolysis, and Immobilization

Vascular Disease

  • Congenital Venous Malformation of the Inferior Vena Cava
  • Lower Extremity Venous Insufficiency (see Lower Extremity Chronic Venous Disease)
  • May-Thurner Syndrome (May-Thurner Syndrome)
    • Physiology
      • Compression of the Left Common Iliac Vein Between the Overlying Right Common Iliac Artery and Underlying Vertebral Body
  • Paget-Schroetter Syndrome (see Paget-Schroetter Syndrome)
    • Physiology
      • Underlying Venous Compression at the Thoracic Outlet
  • Superficial Thrombophlebitis/Superficial Venous Thrombosis (SVT) (see Superficial Venous Thrombosis)
    • Epidemiology
      • Superficial Venous Thrombosis May Occur in Patients with Inherited/Acquired Hypercoagulable States
      • Superficial Venous Thrombosis a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
    • Clinical
      • Occult Deep Venous Thrombosis: occult deep venous thrombosis is present in 7-32% of superficial thrombophlebitis cases (suggests that screening of these patients with lower extremity dopplers may be warranted)
      • Recurrence of Superficial Venous Thrombosis: 24% of cases have recurrent superficial venous thrombosis (Thromb Haemost, 1999) [MEDLINE]
      • Later Development of Deep Venous Thrombosis: 32% of superficial venous thrombosis cases develop deep venous thrombosis at median interval of 4 years (Thromb Haemost, 1999) [MEDLINE]
  • Varicose Veins (see Varicose Veins)
    • Epidemiology
      • Varicose Veins are a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]

Drug/Toxin

  • Bevacizumab (Avastin) (see Bevacizumab)
    • Epidemiology
      • Two-Fold Increased Risk of Thromboembolic Disease
    • Physiology
      • MayBe Due to Vascular Injury
    • Clinical
      • May Result in Both Venous and Arterial Events
  • Blood Transfusion
    • Epidemiology
      • Blood Transfusion is a Moderate Risk for Venous Thromboembolism (Odds Ratio 2-9) (Eur Heart J, 2020) [MEDLINE]
  • Chemotherapy
    • Epidemiology
      • Chemotherapy is a Moderate Risk for Venous Thromboembolism (Odds Ratio 2-9) (Eur Heart J, 2020) [MEDLINE]
  • Corticosteroids (see Corticosteroids)
    • Epidemiology
      • Dutch Population-Based Case-Control Study of Danish Adults (Over 7 Year Period) [MEDLINE]: n= 38,765 Danish adults who developed venous thromboembolism (with n = 387,650 controls)
        • Systemic vs Non-Systemic Steroids: risk of venous thromboembolism was highest with use of systemic glucocorticoids, as compared to a relatively lower risk with inhaled or gastrointestinal glucocorticoids
        • Time of Onset-Related Effect: risk of venous thromboembolism was highest with new use of glucocorticoids (incidence ratio 3.06), as compared to continuing or past use
        • Dose-Effect: risk of venous thromboembolism increased with increasing cumulative doses of the glucocorticoids
        • Possible Study Flaws Include that the Study Did Not Fully Account for All of the Confounding Risks of Venous Thromboembolism Related to the Underlying Disease Itself (For Which the Glucocorticoids were Prescribed): consequently, the underlying disease may have increased the risk of venous thromboembolism or the increased risk of immobility (which could indirectly increase the risk of venous thromboembolism)
      • United States Population-Based Retrospective Cohort Study of the Risks of Short-Term Corticosteroid Use in Adults (BMJ, 2017) [MEDLINE]
        • One in Five American Adults in a Commercially-Insured Plan were Given at Least One Outpatient Short-Term Corticosteroid Course During the Three Year Study (2012-2014): mostly for upper respiratory tract infections, spinal conditions, and allergies
        • Within 30 Days of Initiation, Short-Term Use of Corticosteroids Increased the Risk of Sepsis (Incidence Rate Ratio 5.30, 95% CI: 3.80-7.41), Venous Thromboembolism (Incidence Rate Ratio 3.33, 95% CI: 2.78-3.99), and Fractures (Incidence Rate Ratio 1.87, 95% CI: 1.69-2.07): increased risk persisted at prednisone equivalent doses of <20 mg/day (incidence rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture)
  • Erythropoiesis-Stimulating Agents
    • Epidemiology
      • Erythropoiesis-Stimulating Agents are a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
    • Agents
  • Heparin-Induced Thrombocytopenia (HIT) (see Heparin)
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Hormone Replacement Therapy (see Estrogen)
    • Epidemiology
      • Hormone Replacement Therapy is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
    • Diagnosis
      • Some Cases Manifest Abnormal Activated Protein C (APC) Resistance Assay
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Injection Drug Abuse (see Injection Drug Abuse)
    • Physiology
      • Due to Femoral Injection of Drugs
  • Lenalidomide (Revlimid) (see Lenalidomide)
  • Nonsteroidal Anti-Inflammatory Drugs (NSAID’s) (see Nonsteroidal Anti-Inflammatory Drug)
    • Epidemiology
      • In a Systematic Review and Meta-Analysis, NSAID’s Increased the Risk of Venous Thromboembolism with Relative Risk of 1.80 (95% CI: 1.28-2.52) (Rheumatology, 2015) [MEDLINE]
  • Oral Contraceptives (OCP) (see Oral Contraceptives)
    • Epidemiology
      • Oral Contraceptives are a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]
    • Diagnosis
      • Some Cases Manifest Abnormal Activated Protein C (APC) Resistance Assay
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Prothrombin Complex Concentrate-3 Factor (Profilnine SD) (see Prothrombin Complex Concentrate-3 Factor)
  • Prothrombin Complex Concentrate-4 Factor (Kcentra, Beriplex, Confidex) (see Prothrombin Complex Concentrate-4 Factor)
  • Tamoxifen (see Tamoxifen)
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Testosterone (see Testosterone)
  • Thalidomide (see Thalidomide)
  • Tobacco Abuse (see Tobacco)
    • Epidemiology
      • Longitudinal Investigation of Thromboembolism Etiology (LITE) Study Indicated that Alcohol Use, Hypertension, Hyperlipidemia, Physical Inactivity, and Tobacco Abuse were Not Associated with an Increased Risk of Venous Thromboembolism (Arch Intern Med, 2002) [MEDLINE]
      • Meta-Analysis Indicated that Obesity (Risk 2.33), Hypertension (Risk 1.51), Diabetes Mellitus (Risk 1.42), Smoking (Risk 1.15), and Hypercholesterolemia (Risk 1.16) Increased the Risk of Venous Thromboembolism (Circulation, 2008) [MEDLINE]
  • Tofacitinib (Xeljanz) (see Tofacitinib)
    • Epidemiology
      • Increased Risk of Pulmonary Embolism Has Been Reported with Higher Tofacitinib Doses (10 mg BID) (JAMA, 2019) [MEDLINE]
        • The High Dose 10 mg BID Regimen is FDA-Approved Only for Ulcerative Colitis (see Ulcerative Colitis)

Other

  • Acquired Thrombotic Thrombocytopenic Purpura (TTP) (see Thrombotic Thrombocytopenic Purpura-Acquired)
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Activated Protein C (APC) Resistance (Non-Genetic)
  • Age
    • Epidemiology
      • Hazard Ratio of 1.7 (95% Confidence Interval: 1.5 to 2.0) for Every Decade of Life After Age 55 (Arch Intern Med, 2002) [MEDLINE]
      • Increased Age is a Weak Risk Factor for Venous Thromboembolism (with Odds Ratio <2) (Eur Heart J, 2020) [MEDLINE]
  • Antiphospholipid Antibody Syndrome (see Antiphospholipid Antibody Syndrome)
    • Diagnosis
      • Some Cases Manifest Abnormal Activated Protein C (APC) Resistance Assay
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Asthma (see Asthma)
  • Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Hyperhomocysteinemia (see Hyperhomocysteinemia)
  • Hyperlipidemia (see Hyperlipidemia)
    • Epidemiology
      • Longitudinal Investigation of Thromboembolism Etiology (LITE) Study Indicated that Alcohol Use, Hypertension, Hyperlipidemia, Physical Inactivity, and Tobacco Abuse were Not Associated with an Increased Risk of Venous Thromboembolism (Arch Intern Med, 2002) [MEDLINE]
      • Meta-Analysis Indicated that Obesity (Risk 2.33), Hypertension (Risk 1.51), Diabetes Mellitus (Risk 1.42), Smoking (Risk 1.15), and Hypercholesterolemia (Risk 1.16) Increased the Risk of Venous Thromboembolism (Circulation, 2008) [MEDLINE]
  • Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea)
  • Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria)
    • Clinical
      • May Result in Both Venous and Arterial Thromboses
  • Prior Thrombotic Event
    • Epidemiology
      • Prior Venous Thromboembolism is a Strong Risk Factor for Venous Thromboembolism (with Odds Ratio >10) (Eur Heart J, 2020) [MEDLINE]
  • Respiratory Failure (see Respiratory Failure)
    • Epidemiology
      • Respiratory Failure is a Moderate Risk Factor for Venous Thromboembolism (with Odds Ratio >2-9) (Eur Heart J, 2020) [MEDLINE]

Lower Extremity Venous Anatomy

Superficial Veins

  • Greater Saphenous Vein Above or Below the Knee
  • Non-Saphenous Veins
  • Small Saphenous Vein
  • Telangiectasias/Reticular Veins

Deep Veins

  • Inferior Vena Cava (IVC)
  • Iliac Veins
    • Common Iliac Vein
    • External Iliac Vein
    • Internal Iliac Vein
  • Pelvic Veins
    • Broad Ligament Vein
    • Gonadal Vein
    • Other Pelvic Veins
  • Femoral Veins
    • Common Femoral Vein
    • Deep Femoral Vein
  • Popliteal Vein
  • Crural Calf Veins
    • Anterior Tibial Vein: less common site of distal DVT
    • Posterior Tibial Vein: more common site of distal DVT
    • Peroneal Vein: more common site of distal DVT
  • Muscular Calf Veins: less common site of distal DVT
    • Gastrocnemius Vein
    • Soleal Vein
    • Other Muscular Calf Veins

Perforator Veins

  • Thigh Perforator Vein
  • Calf Perforator Vein

Upper Extremity Venous Anatomy

Superficial Veins

  • Basilic Vein
    • Common site of PICC placement
  • Cephalic Vein
  • Median Antebrachial Vein
  • Median Antecubital Vein
  • Accessory Cephalic Vein

Deep Veins

  • Radial Vein
  • Ulnar Vein
  • Interosseous Vein: in the forearm
  • Brachial Vein
    • Common site for PICC-related DVT
  • Axillary Vein
    • Common site for PICC-related DVT
  • Subclavian Vein
    • Common site for PICC-related DVT
  • Internal Jugular Vein
    • Most common site for CVC-related deep venous thrombosis

Physiology

Upper Extremity Deep Venous Thrombosis

Lower Extremity Deep Venous Thrombosis


Diagnosis

Plasma D-Dimer (see Plasma D-Dimer)

Assay

Interpretation

Clinical Efficacy

Recommendations (American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guidelines for the Evaluation of Suspected Pulmonary Embolism in Pregnancy) (Am J Respir Crit Care Med, 2011) [MEDLINE]

Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]

Lower Extremity Venogram (see Lower Extremity Venogram)

Lower Extremity Compression Venous Doppler Ultrasound (see Lower Extremity Compression Venous Doppler Ultrasound)

Clinical Efficacy-Occlusiveness of Deep Venous Thrombosis

Clinical Efficacy-Other

Recommendations (American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guidelines for the Evaluation of Suspected Pulmonary Embolism in Pregnancy) (Am J Respir Crit Care Med, 2011) [MEDLINE]

Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]

Upper Extremity Compression Venous Doppler Ultrasound (see Upper Extremity Compression Venous Doppler Ultrasound)

Clinical Efficacy

Recommendations

Computed Tomography (CT) Lower Extremity Venogram (see Computed Tomography Lower Extremity Venogram)

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]

Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]

Computed Tomography (CT) Upper Extremity Venogram (see Computed Tomography Upper Extremity Venogram)

Gadolinium-Enhanced Magnetic Resonance Venogram and Pulmonary Artery Angiogram (MRA) (see Magnetic Resonance Imaging)

Advantages

Disadvantages

Recommendations

Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]

Gadolinium-Enhanced Magnetic Resonance Upper Extremity Venogram (see Magnetic Resonance Upper Extremity Venogram)

Lower Extremity Impedance Plethysmography (IPG)

Lower Extremity Radiofibrinogen Study

Recommendations for Diagnostic Testing for Suspected Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]

Recommended Diagnostic Testing for Suspected First Lower Extremity Deep Venous Thrombosis if Risk Stratification is NOT USED to Classify Patient (By Pretest Probability)

Recommended Diagnostic Testing for Suspected First Lower Extremity Deep Venous Thrombosis if Risk Stratification is USED to Classify Patient (By Pretest Probability)

Recommended Diagnostic Testing for Suspected Recurrent Lower Extremity Deep Venous Thrombosis

Recommended Diagnostic Testing for Suspected Pregnancy-Associated Lower Extremity Deep Venous Thrombosis

Recommendations for Diagnostic Testing for Suspected Upper Extremity Deep Venous Thrombosis

Clinical Evaluation for Suspected Pulmonary Embolism in Pregnancy (see Pregnancy)

Clinical Efficacy

Recommendations (American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guidelines for the Evaluation of Suspected Pulmonary Embolism in Pregnancy) (Am J Respir Crit Care Med, 2011) [MEDLINE]


Clinical Manifestations of Lower Extremity Deep Venous Thrombosis

General Comments

Anatomic Site of Deep Venous Thrombosis (DVT)

  • Proximal Deep Venous Thrombosis (DVT)
    • Femoral Veins
    • Iliac Veins
    • Popliteal Veins
  • Distal (Calf) Deep Venous Thrombosis (DVT)
    • Crural Calf Veins
      • Anterior Tibial Veins
      • Posterior Tibial Veins
      • Peroneal Veins
    • Muscular Calf Veins
      • Gastrocnemius Veins
      • Soleal Veins
      • Other Muscular Calf Veins

Provoked vs Unprovoked Deep Venous Thrombosis (DVT)

  • Provoked Deep Venous Thrombosis: deep venous thrombosis attributable to an identifiable etiology or provoking event
  • Unprovoked Deep Venous Thrombosis: deep venous thrombosis with no identifiable etiology or provoking event

Symptomatic vs Asymptomatic Deep Venous Thrombosis (DVT)

  • Asymptomatic Deep Venous Thrombosis: DVT diagnosed with a lack of clinical symptoms (ie incidentally diagnosed on radiologic study performed in an asymptomatic patient)
  • Symptomatic Deep Venous Thrombosis: presence of clinical symptoms that would lead to the radiologic diagnosis of DVT

Cardiovascular Manifestations

Atrial Fibrillation (AF) (see Atrial Fibrillation)

  • Epidemiology
    • Norwegian Tromso Study of the Association Between Venous Thromboembolism and Atrial Fibrillation (J Am Heart Assoc, 2014) [MEDLINE]
      • Venous Thromboembolism was Associated with an Increased Future Risk of Atrial Fibrillation: 9.3% of patients with venous thromboembolism developed subsequent atrial fibrillation
      • Risk of Atrial Fibrillation was Particularly High in the First 6 Months After the Venous Thomboembolism Event (Hazard Ratio 4.00, 95% CI: 2.21-7.25) and in Those with Pulmonary Embolism (Hazard Ratio 1.78, 95% CI: 1.13-2.8)

Rheumatologic/Orthopedic/Vascular Manifestations

Lower Extremity Pain (see Lower Extremity Pain)

  • Epidemiology
    • Lower Extremity Pain is Common

Peripheral Edema (see Peripheral Edema)

  • Epidemiology
    • Peripheral Edema (Particularly Unilateral) is Common

Free-Floating Deep Venous Thrombosis

  • Clinical Data
    • Study of Clinical Significance of Free-Floating Thrombus (J Vasc Surg, 1990) [MEDLINE]
      • Free-Floating Thrombus Occurred in 10% of Cases of Acute Deep Venous Thrombosis
      • Only 13% of Free-Floating Thrombi were Associated with Clinically Significant Pulmonary Embolism (by Ventilation-Perfusion Scanning)
      • When Followed by Serial Lower Extremity Dopplers, Most Free-Floating Thrombi Do Not Embolize, But Rather They Become Attached to the Vein Wall or Resolve
    • French Prospective Trial Examining the Impact of Detecting Free-Floating Thrombus (on Lower Extremity Doppler Ultrasound) in Deep Venous Thrombosis (Arch Intern Med, 1997) [MEDLINE]
      • Doppler Ultrasound Had a Sensitivity of 68% and a Specificity of 86% for the Diagnosis of Free-Floating Thrombus on Doppler Ultrasound
      • In the Setting of Appropriate Anticoagulation Therapy (Almost All of the Subjects Received the Low Molecular Weight Heparin, Nadroparin, and Only One Subject Received Unfractionated Heparin Drip), the Presence of Free-Floating Thrombus on a Lower Extremity Doppler Study Did Not Increase the Risk of Acute Pulmonary Embolism (At Day 10, the Incidence of Pulmonary Embolism was 3% in Free-Floating Group vs 4% in the Occlusive Group; p = 0.92)
      • Importantly, the Trial was Performed in 1992-1993 (Using Only Unfractionated Heparin and Low Molecular Weight Heparin) and the Results Cannot Be Applied to Patients Who Receive Direct Oral Anticoagulants (DOAC’s), Which Were Not Available for Use at That Time

Phlegmasia Cerulea Dolens

  • Epidemiology
    • Age: peak in 5th-6th decade of life
    • Sex: F>M
  • Precipitating Factors
  • Physiology
    • Acute Massive Proximal (Iliofemoral) Venous Thrombosis with Obstructed Venous Drainage of Lower Extremity
    • Left Lower Extremity Involvement
      • Left Lower Extremity is Involved 3-4x as Often as the Right Lower Extremity
    • Upper Extremity Involvement
      • Upper Extremity Involvement Occurs in <5% of Cases
  • Clinical Manifestations
    • Blebs/Bullous Skin Lesions (see Vesicular-Bullous-Pustular Skin Lesions)
    • Peripheral Edema (see Peripheral Edema)
    • Cyanosis (Cerulea) (see Cyanosis)
      • Cyanosis is Usually a Characteristic Finding
      • Progresses from Distal to Proximal Lower Extremity
    • Phlegmasia Alba Dolens: blanching (alba) without cyanosis
    • Sudden Onset of Severe Lower Extremity Pain (see Lower Extremity Pain)
      • Pain is Usually Constant and Severe (Usually Starts at the Femoral Triangle and Progresses to Involve the Entire Lower Extremity)
      • Symptoms May be Gradual in Onset in Some Cases
    • Venous Gangrene
      • Venous Gangrene is a Late Finding
    • Extremity Compartment Syndrome (see Extremity Compartment Syndrome)

Post-Thrombotic (Post-Phlebitic) Syndrome

  • Epidemiology
    • XXXXX
  • Clinical
    • XXXX

Other Manifestations

Fever (see Fever)

  • Epidemiology
    • Study of Data from the RIETE Registry of Symptomatic Deep Venous Thrombosis Cases (J Thromb Thrombolysis, 2011) [MEDLINE]: n = 14,480
      • Fever was Present (at Presentation) in 4.9% of Symptomatic Deep Venous Thrombosis Cases
      • Patients Initially Presenting with Fever Had a Higher Mortality Rate, as Compared to Those without Fever (5.8% vs 2.9%; Odds Ratio 2.6; 95% CI: 1.9-3.5)
      • Among the Causes of Death, Pulmonary Embolism (0.7% vs 0.1%) and Infection (1.1% vs 0.3%) were Significantly More Common in Symptomatic Deep Venous Thrombosis Patients Presenting with Fever
      • Multivariate Analysis Confirmed that Deep Venous Thrombosis Patients with Fever Had an Increased Mortality (Hazard Ratio 2.00; 95% CI: 1.44-2.77), Irrespective of the Patient Age, Body Weight, and Risk Factors for Venous Thromboembolism

Clinical Manifestations of Upper Extremity Deep Venous Thrombosis

Rheumatologic/Orthopedic Manifestations

Upper Extremity Pain (see Upper Extremity Pain)

  • xxxxx

Upper Extremity Peripheral Edema (see Peripheral Edema)

  • xxxx

Prophylaxis

High-Risk Medical Patients

Rationale

  • Patients Remain at Increased Risk for Venous Thromboembolism for Up to 3 Months Following Hospital Discharge (Mayo Clin Proc, 2001) [MEDLINE]
    • Peak Risk for Venous Thromboembolism Appears to Be with the First 4 Weeks Following Hospital Discharge (Mayo Clin Proc, 2001) [MEDLINE]

Methods of Deep Venous Thrombosis Prophylaxis in High-Risk Medical Patients

Clinical Efficacy-General

  • Randomized EXCLAIM Trial of Extended-Duration Enoxaparin (28 +/- 4 Days, After Receiving Open Label Enoxaparin for an Initial 10 +/4 Days) in Acutely Ill Medical Patients with Decreased Mobility (Ann Intern Med, 2010) [MEDLINE]
    • Extended-Duration Enoxaparin Decreases VTE More than it Increases Major Bleeding Events in Acutely Ill Medical Patients with Level 1 Immobility, Tose >75 y/o, and Women
  • International Economic Evaluation of Pharmacologic Deep Venous Thrombosis Prophylaxis vs Weekly Ultrasound Screening in Intensive Care Unit Patients in Canada/US/Australia (Am J Resp Crit Care Med, 2011) [MEDLINE]
    • Study Used Markov Decision Analysis Comparing Weekly Ultrasound Screening (Case Finding) to Pharmacologic Prophylaxis (Limitation: There are No Randomized Trials Examining Screening for Deep Venous Thrombosis in Critically Ill Patients)
    • In ICU Patients Who Received Standard Deep Venous Thrombosis Prophylaxis, Weekly Doppler Compression Ultrasound Screening Cost >$200k/QALY (At >50-$100k/QALY, This is Not Considered Cost-Effective)
      • Although Increased Venous Thromboembolism Detection was Noted, Screening was Associated with More Bleeding Events (Due to a Greater Frequency of Anticoagulation and Higher Number of False-Positive Studies for Deep Venous Thrombosis)
      • Very Small Improvements in Quality-Adjusted Survival Did Not Justify the Additional Costs of Routine Weekly Screening
    • Appropriate Pharmacologic Prophylaxis Combined with Deep Venous Thrombosis Case Finding was at Least as Effective, Less Time-Consuming, and Less Expensive than Routine Weekly Ultrasound Screening
    • Agrees with Prior Study Which Failed to Demonstrate Benefit of Routine Ultrasound Deep Venous Thrombosis Screening in Critically Ill Patients (Although Weekly Ultrasound Screening was Found Effective in Subset with Femoral Central Venous Catheters) (Am J Resp Crit Care Med, 2003) [MEDLINE]
    • However, when the Risk of Proximal Deep Venous Thrombosis During Critical Illness was ≥16%, Ultrasound Screening Cost <$50k/QALY and was Cost-Effective
      • In Patients with Multiple Trauma, Acute Brain/Spinal Cord Injury, Cancer, and in Critically Ill Patients Who Do Not Receive Pharmacologic Prophylaxis, the Risk of Deep Venous Thrombosis May Approach the 16% Level (Arch Intern Med, 2001) [MEDLINE]
      • In a Study of Critically Injured Trauma Patients Who Did Not Receive Pharmacologic Prophylaxis, the Risk of Proximal DVT was 18% (NEJM, 1994) [MEDLINE]
    • Therefore, in Intensive Care Unit Patients, Pharmacologic Deep Venous Thrombosis Prophylaxis Should Be Provided (if Possible)
      • However, in Select High-Risk Patient Populations (as Noted Above), Weekly Ultrasound Screening May Be Cost-Effective
  • LIFENOX Trial of Enoxaparin with Elastic Graduated Compression Stockings vs Elastic Graduated Compression Stockings Alone Hospitalized Acutely Ill Medical Patients (NEJM, 2011) [MEDLINE]: RCT (n = 8307)
    • In Hospitalized Acutely Ill Medical Patients, Enoxaparin Plus Elastic Graduated Compression Stockings, as Compared with Elastic Graduated Compression Stockings Alone, was Not Associated with Decreased All-Cause Mortality Rate
  • PROTECT Trial of Dalteparin vs Unfractionated Heparin Deep Venous Thrombosis Prophylaxis (NEJM, 2011) [MEDLINE]: n = 1873
    • Dalteparin was Not Superior to Unfractionated Heparin Deep Venous Thrombosis Prophylaxis, in Terms of Incidence of Proximal Deep Venous Thrombosis
  • Economic Evaluation of Data Derived from the PROTECT Trial (JAMA, 2014) [MEDLINE]: n = 2,344 (23 centers in 5 countries)
    • In Critically Ill Medical-Surgical Patients Undergoing Pharmacologic Deep Venous Thrombosis Prophylaxis, Dalteparin Had a Lower Acute Pulmonary Embolism Rate, Lower Heparin-Induced Thrombocytopenia (HIT) Rate, and Similar or Lower Cost, as Compared to Unfractionated Heparin Deep Venous Thrombosis Prophylaxis
  • Systematic Review and Network Meta-Analysis of Deep Venous Thrombosis Prophylaxis in Acutely Ill Hospitalized Inpatients (BMJ, 2022) [MEDLINE]: n = 90,095 (44 randomized controlled trials)
    • Evidence of Low-Moderate Quality Indicated that None of the Interventions Decreased All-Cause Mortality, as Compared to Placebo
    • Low-Molecular Weight Heparin in an Intermediate Dose Conferred the Best Balance of Benefits/Harms for Prevention of Venous Thromboembolism
    • Unfractionated Heparin (in Particular the Intermediate Dose) and Direct Oral Anticoagulants Had the Least Favorable Profile
    • Main Limitations of This Study Include the Quality of Evidence (Which was Generally Low-Moderate Due to Imprecision and Within-Study Bias) and Statistical Inconsistency

Clinical Efficacy-Deep Venous Thrombosis Prophylaxis in the Setting of Critical Illness

  • Systematic Review and Meta-Analysis of Venous Thromboembolism Prophylaxis in Critically Ill Adults (Chest, 2022) [MEDLINE]: n = 9,619 (from 13 randomized controlled trials)
    • Low Molecular Weight Heparin Decreased the Incidence of Deep Venous Thrombosis (Odds Ratio 0.59; 95% Credible Interval: 0.33-0.90; High Certainty), as Compared to Control (Either No Prophylaxis, Placebo, or Compression Stockings Only)
    • Unfractionated Heparin May Have Decreased the Incidence of Deep Venous Thrombosis (Odds Ratio 0.82; 95% Credible Interval: 0.47-1.37; Low Certainty), as Compared to Control
    • Mechanical Compressive Devices May Have Decreased the Incidence of Deep Venous Thrombosis (Odds Ratio 0.85; Credible Interval: 0.50-1.50; Low Certainty), as Compared to Control
    • Low Molecular Weight Heparin was Probably More Effective than Unfractionated Heparin in Decreasing the Incidence of Deep Venous Thrombosis (Odds Ratio 0.72 [95% Credible Interval: 0.46-0.98; Moderate Certainty)
      • Low Molecular Weight Heparin Should Be Considered the Primary Pharmacologic Agent for Thromboprophylaxis
    • Combination Pharmacologic Therapy and Mechanical Compressive Devices Demonstrated an Unclear Effect on the Incidence of Deep Venous Thrombosis, as Compared with Either Therapy Alone (Very Low Certainty)

Clinical Efficacy-Deep Venous Thrombosis Prophylaxis in the Setting of Low Body Weight and Obesity

  • Study of High-Dose Heparin Deep Venous Thrombosis Prophylaxis in Hospitalized Morbidly Obese Patients (>100 kg and BMI ≥40) (Thromb Haemost, 2014) [MEDLINE]: n = 3,928
    • High-Dose Heparin Deep Venous Thrombosis (Unfractionated Heparin 7500 U TID or Enoxaparin 40 mg BID) Halved the Odds of Symptomatic Venous Thromboembolism (0.77%), as Compared to Standard Dose Heparin Deep Venous Thrombosis (Unfractionated Heparin 5000 U BID/TID or Enoxaparin 40 mg qday) (1.48%) (Odds Ratio 0.52; 95% Confidence Interval: 0.27-1.00; p = 0.050)
    • Bleeding Rates were Similar in Both Groups
  • Retrospective Study of High-Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis in Overweight Neurocritical Care Patients (>100 kg) (J Thromb Thrombolysis, 2015) [MEDLINE]
    • High-Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis Group (7500 U q8hrs) and Standard Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis Group (5000 U q8hrs) Had Similar Venous Thromboembolism Rates
    • Both Groups Had Similar Rates of Bleeding Complications
  • Single-Center Retrospective Studies of DVT Prophylaxis in Hospitalized Overweight/Obese Patients (>100 kg) (Pharmacotherapy, 2016) [MEDLINE]: n = 1,335
    • High-Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis (7500 U q8hrs), as Compared to Standard Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis (5000 U q8hrs) Had Similar Venous Thromboembolism Rates for All BMI Classes (BMI 25-29.9 kg/m2, BMI 30-34.9 kg/m2, BMI 35-39.9 kg/m2, and BMI ≥ 40 kg/m2)
    • Bleeding Rate was Higher in the High-Dose Group
  • Literature Review of Enoxaparin Dosing for Patients at Extremes of Weight (Ann Pharmacother, 2018) [MEDLINE]
    • Low Body Weight Patients May Benefit from Enoxaparin 30 mg SQ qday for Venous Thromboembolism Prophylaxis, and Standard Weight-Based Dosing for Venous Thromboembolism Treatment
    • In Patients with BMI ≥40 kg/m2, Enoxaparin 40 mg SQ BID is Recommended for Venous Thromboembolism Prophylaxis
    • In Patients with BMI ≥50 kg/m2, Consideration Should Be Given for Higher Doses for Venous Thromboembolism Prophylaxis

Clinical Efficacy-Apixaban (Eliquis) (see Apixaban)

  • ADOPT Trial Examining Prolonged Apixaban (For 30 Days) vs Enoxaparin (For ≥6 Days) for Deep Venous Thrombosis Prophylaxis After Hospital Discharge in Medical Patients (NEJM, 2011) [MEDLINE]: double-blind, double-dummy, placebo-controlled trial (n = 6528)
    • In Medically Ill Patients, an Extended Course of Apixaban Deep Venous Thrombosis Prophylaxis was not Superior to a Shorter Course with Enoxaparin
    • Apixaban was Associated with Significantly More Major Bleeding Events (0.47%) than Enoxaparin (0.19%) at Day 30

Clinical Efficacy-Betrixaban (see Betrixaban)

  • APEX Trial of Extended-Duration Betrixaban (35-42 Days) After Initial Enoxaparin (x 10 +/- 4 Days) for DVT Prophylaxis in Hospitalized, Acutely Ill Medical Patients (Am Heart J, 2017) [MEDLINE]: randomized, double-blind, double-dummy, active-controlled, multi-national
    • Betrixaban (Only at the Higher Dose of 80 mg) + Initial Enoxaparin (x 10 +/- 4 Days) was Superior to Initial Enoxaparin Alone (x 10 +/- 4 Days), in Terms of Venous Thromboembolism at Day 42, without an Increased Risk of Bleeding

Clinical Efficacy-Rivaroxaban (Xarelto) (see Rivaroxaban)

  • MAGELLAN Non-Inferiority Trial Comparing Rivaroxaban (x 35 +/- 4 Days) to Enoxaparin (x 10 +/- 4 Days) for DVT Prophylaxis in Acutely Ill Medical Patients (NEJM, 2013) [MEDLINE]: multi-center, randomized ( n = 8101)
    • At Day 10: Rivaroxaban was Equivalent (2.7%) to Enoxaparin (2.7%), in Terms of Venous Thromboembolism
    • At Day 35: Rivaroxaban was Superior (4.4%) to Enoxaparin (5.7%), in Terms of Venous Thromboembolism
    • At Day 10: Rivaroxaban Had Significantly Higher Bleeding Risk (2.8%) vs Enoxaparin (1.2%)
    • At Day 35: Rivaroxaban Had Significantly Higher Bleeding Risk (4.1%) vs Enoxaparin (1.7%)
  • MARINER Trial of Prophylactic Rivaroxaban Begun and Continuing After Hospital Discharge (x 45 Days) in High-Risk Medical Patients (Thromb Haemost, 2016) [MEDLINE]: randomized, double-blind, placebo-controlled
    • In Process: endpoints of symptomatic VTE and VTE-related death

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]

  • Asymptomatic Hypercoagulable State
    • Mechanical/Pharmacologic Prophylaxis is Not Recommended (Grade 1C Recommendation)
  • Chronically Immobilized Patients
    • Pharmacologic Prophylaxis is Not Recommended (Grade 2C Recommendation)
  • Critically Ill Patients
    • For Critically Ill Patients Routine Ultrasound Screening for Deep Venous Thrombosis is Not Recommended (Grade 2B Recommendation)
    • Low Molecular Weight Heparin or Low Dose Unfractionated Heparin Prophylaxis is Recommended (Grade 2C Recommendation)
    • For Critically Ill Patients with High Risk for Major Hemorrhage, Graduated Compression Stockings/Sequential Compression Devices are Recommended Until Bleeding Risk Decreases (at Which Time Pharmacologic Prophylaxis Should Be Substituted for Mechanical Prophylaxis) (Grade 2C Recommendation)
  • Hospitalized Acutely Ill Medical Patients
    • Hospitalized Acutely Ill Medical Patients with High Risk of Thrombosis, Low Molecular Weight Heparin, Low Dose Unfractionated Heparin Prophylaxis BID/TID, or Fondaparinux is Recommended (Grade 1B Recommendation)
    • For Hospitalized Acutely Ill Medical Patients with High Risk of Thrombosis and High Risk for Major Hemorrhage, Graduated Compression Stockings/Sequential Compression Devices are Recommended Until Bleeding Risk Decreases (at Which Time Pharmacologic Prophylaxis Should Be Substituted for Mechanical Prophylaxis) (Grade 2C Recommendation)
    • Hospitalized Acutely Ill Medical Patients with Low Risk of Thrombosis, No Pharmacologic or Mechanical Prophylaxis is Recommended
    • For Hospitalized Acutely Ill Medical Patients Who Receive an Initial Course of Prophylaxis, Extension of Duration Beyond the Period of Patient Immobilization or the Acute Hospital Stay is Not Recommended (Grade 2B Recommendation)
  • Persons Traveling Long Distance with Increased Risk of Venous Thrombembolism (Active Malignancy, Advanced Age, Estrogen Use, Known Hypercoagulable State, Limited Mobility, Pregnancy, Previous Venous Thromboembolism, Recent Surgery/Trauma, Severe Obesity)
    • Graduated Venous Compression Stockings (with 15-30 mm Hg of Pressure at the Ankle) are Recommended (Grade 2C Recommendation)

Other Recommendations

  • Deep Venous Thrombosis Prophylaxis in the Setting of Obesity
    • Unfractionated Heparin (Thromb Haemost, 2014) [MEDLINE] (J Thromb Thrombolysis, 2015) [MEDLINE] (Pharmacotherapy, 2016) [MEDLINE]
      • Heparin 5000-7500 U BID SQ is Probably Preferred (with Individualized Dosing Considered for Specific Patients)
    • Enoxaparin (Lovenox) (Obes Surg, 2002) [MEDLINE] (Surg Obes Relat Dis, 2008) [MEDLINE]
      • BMI 30-39 kg/m2: enoxaparin 30 mg q12hrs or 40 mg qday
      • BMI ≥40 kg/m2: enoxaparin 40 mg q12hrs
      • High Venous Thromboembolism-Risk Bariatric Surgery with BMI ≤50 kg/m2: enoxaparin 40 mg q12hrs
      • High Venous Thromboembolism-Risk Bariatric Surgery with BMI >50 kg/m2: enoxaparin 60 mg q12hrs

Abdominal-Pelvic Surgery Patients

Clinical Efficacy

  • Systematic Review of Risk of Heparin-Induced Thrombocytopenia in Post-Operative Patients Comparing Unfractionated Heparin vs Low Molecular Weight Heparin DVT Prophlaxis (Cochrane Database Syst Rev, 2012) [MEDLINE]
    • Lower incidence of HIT and HIT Complicated by Venous Thromboembolism in Postoperative Patients Undergoing Low Molecular Weight Heparin DVT Prophylaxis, as Compared to Unfractionated Heparin DVT Prophylaxis
  • Economic Evaluation Data Derived from PROTECT Trial (JAMA, 2014) [MEDLINE]: economic evaluation of dalteparin vs unfractionated heparin prophylaxis in medical and surgical critically ill patients (n = 2344 in 23 centers in 5 countries)
    • In Critically Ill Medical-Surgical Patients Undergoing Pharmacologic DVT Prophylaxis, Dalteparin Exhibited a Lower PE Rate, Lower Heparin-Induced Thromobcytopenia (HIT) Rate, and Similar or Lower Cost, as Compared to Unfractionated Heparin DVT Prophylaxis

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Low Risk General/Abdominal-Pelvic Surgery (Approximately 1.5%; Rogers Score: 7-10; Caprini Score: 1-2)
    • Mechanical Prophylaxis (Preferably Sequential Compression Devices) is Recommended (Grade 2C Recommendation)
  • Moderate Risk General/Abdominal-Pelvic Surgery (Approximately 3.0%; Rogers Score: >10; Caprini Score: 3-4) without High Risk for Major Bleeding
    • Low Molecular Weight Heparin (Grade 2B Recommendation), Low Dose Unfractionated Heparin (Grade 2B Recommendation), or mechanical prophylaxis (preferably sequential compression devices) (Grade 2C Recommendation) are recommended
  • Moderate Risk General/Abdominal-Pelvic Surgery (Approximately 3.0%; Rogers Score: >10; Caprini Score: 3-4) with High Risk for Major Bleeding
    • Mechanical Prophylaxis (Preferably Sequential Compression Devices) is Recommended (Grade 2C Recommendation)
  • High Risk General/Abdominal-Pelvic Surgery (Approximately 6.0%; Caprini Score: At Least 5) without High Risk for Major Bleeding
    • Low Molecular Weight Heparin (Grade 1B Recommendation) or Low Dose Unfractionated Heparin (Grade 1B Recommendation), AND mechanical prophylaxis (preferably sequential compression devices)
  • High Risk General/Abdominal-Pelvic Surgery (Approximately 6.0%; Caprini Score: At Least 5) with High Risk for Major Bleeding
    • Mechanical Prophylaxis (Preferably Sequential Compression Devices) is Recommended (Grade 2C Recommendation)

Cardiac Surgery Patients

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Cardiac Surgery with Uncomplicated Post-Operative Course: mechanical prophylaxis (preferably sequential compression devices) is recommended (Grade 2C Recommendation)
  • Cardiac Surgery with Hospital Course Complicated by One or More Non-Hemorrhagic Surgical Complications: mechanical prophylaxis (preferably sequential compression devices) AND either low-dose unfractionated heparin or low molecular weight heparin prophylaxis is recommended (Grade 2C Recommendation)

Thoracic Surgery Patients

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Thoracic Surgery with Moderate Risk of Venous Thromboembolism (Without Risk for Post-Operative Hemorrhage): sequential compression devices (Grade 2C Recommendation), low-dose unfractionated heparin (Grade 2B Recommendation), or low molecular weight heparin prophylaxis (Grade 2B Recommendation) is recommended

Craniotomy Patients

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Craniotomy: mechanical prophylaxis (preferably sequential compression devices) is recommended (Grade 2C Recommendation)
  • Craniotomy with Very High Risk for Venous Thromboembolism (Craniotomy Performed for Malignant Disease): mechanical prophylaxis (preferably sequential compression devices) is recommended with addition of pharmacologic prophylaxis once hemostasis is established and the risk of bleeding decreases (Grade 2C Recommendation)

Spinal Surgery Patients

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Spinal Surgery: sequential compression devices (Grade 2C Recommendation), low-dose unfractionated heparin (Grade 2C Recommendation), or low molecular weight heparin prophylaxis (Grade 2C Recommendation) is recommended
  • Spinal Surgery with Very High Risk for Venous Thromboembolism (Spinal Surgery Performed for Malignant Disease or Surgery with Combined Anterior-Posterior Approach): mechanical prophylaxis (preferably sequential compression devices) is recommended with addition of pharmacologic prophylaxis once hemostasis is established and the risk of bleeding decreases (Grade 2C Recommendation)

Major Trauma Patients (Traumatic Brain Injury, Traumatic Spinal Injury, Spine Surgery for Trauma)

Clinical Efficacy

  • Cost-Effectiveness Retrospective Analysis of DVT Surveillance in Trauma Patients (n = 4234) in the ICU (PLoS One, 2014) [MEDLINE]
    • Ultrasound Screening of Trauma Patients is Cost-Effective: cost is $29,102/QALY

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Major Trauma: sequential compression devices (Grade 2C Recommendation), low-dose unfractionated heparin (Grade 2C Recommendation), or low molecular weight heparin prophylaxis (Grade 2C Recommendation) is recommended
  • Major Trauma with Very High Risk for Venous Thromboembolism: mechanical prophylaxis (preferably sequential compression devices) should be added to pharmacologic prophylaxis if not contraindicated by lower extremity injury (Grade 2C Recommendation)
  • Major Trauma with Contraindications to Low-Dose Unfractionated Heparin/Low Molecular Weight Heparin: mechanical prophylaxis (preferably sequential compression devices) is recommended (when not contraindicated by presence of lower extremity injury) (Grade 2C Recommendation), with addition of low-dose unfractionated heparin/low molecular weight heparin when bleeding risk decreases or contraindication heparin resolves (Grade 2C)
  • IVC Filter Placement as Primary Prevention of Venous Thromboembolism in Major Trauma: not recommended (Grade 2C Recommendation)
  • Screening Lower Extremity Doppler Ultrasound in Major Trauma: not recommended (Grade 2C Recommendation)

Orthopedic Surgery Patients (Total Hip Arthroplasty, Total Knee Arthroplasty, Hip Fracture Surgery)

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Type of DVT Prophylaxis for Total Hip Arthroplasty/Total Knee Arthroplasty: one of the following is recommended for a minimum of 10-14 days
    • Apixaban (Eliquis) (see Apixaban) (Grade 1B Recommendation)
    • Aspirin (see Acetylsalicylic Acid) (Grade 1B Recommendation)
    • Coumadin (see Coumadin) (Grade 1B Recommendation)
    • Dabigatran (Pradaxa) (see Dabigatran) (Grade 1B Recommendation)
    • Low Molecular Weight Heparin (Grade 1B Recommendation): low molecular weight heparin (if started pre-operatively, started 12 hrs before surgery) is suggested as the preferred agent for DVT prophylaxis (in terms of bleeding risk, efficacy, and long-term safety data) for total hip arthroplasty/total knee arthroplasty (Grade 2C Recommendation vs apixaban/dabigatran/fondaparinux/low-dose unfractionated heparin/rivaroxaban; Grade 2C Recommendation vs aspirin/coumadin)
    • Fondaparinux (Arixtra) (see Fondaparinux) (Grade 1B Recommendation)
    • Low-Dose Unfractionated Heparin Prophylaxis (see Heparin) (Grade 1B Recommendation)
    • Rivaroxaban (Xarelto) (see Rivaroxaban) (Grade 1B Recommendation)
    • Sequential Compression Device (SCD) (see Sequential Compression Device) (Grade 1C Recommendation): suggested to be used alone if bleeding risk contraindicates use of an antithrombotic agent (Grade 2C Recommendation)
  • Type of DVT Prophylaxis Hip Fracture Surgery: one of the following is recommended for 10-14 days
    • Aspirin (see Acetylsalicylic Acid) (Grade 1B Recommendation)
    • Coumadin (see Coumadin) (Grade 1B Recommendation)
    • Low Molecular Weight Heparin (Grade 1B Recommendation): low molecular weight heparin (if started pre-operatively, started at least 12 hrs before surgery) is suggested as the preferred agent for DVT prophylaxis (in terms of bleeding risk, efficacy, and long-term safety data) for hip fracture surgery (Grade 2C Recommendation vs fondaparinux/low-dose unfractionated heparin; Grade 2C Recommendation vs aspirin/coumadin)
    • Fondaparinux (Arixtra) (see Fondaparinux) (Grade 1B Recommendation)
    • Low-Dose Unfractionated Heparin Prophylaxis (see Heparin) (Grade 1B Recommendation)
    • Sequential Compression Device (SCD) (see Sequential Compression Device) (Grade 1C Recommendation): suggested to be used alone if bleeding risk contraindicates use of an antithrombotic agent (Grade 2C Recommendation)
  • Dual DVT Prophylaxis with Antithrombotic Agent and Sequential Compression Device for Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery During the Hospital Stay: recommended (Grade 2C Recommendation)
  • Timing of Initiation of DVT Prophylaxis for Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery: starting DVT prophylaxis at least 12 hrs pre-operatively or 12 or more hrs post-operatively is recommended (Grade 1B Recommendation)
  • Duration of DVT Prophylaxis for Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery: duration of prophylaxis in the outpatient period for up to 35 days from the date of surgery is suggested (Grade 2B Recommendation)
  • IVC Filter Placement as Primary Prevention of Venous Thromboembolism in Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery: not recommended (Grade 2C Recommendation)
  • Screening Lower Extremity Doppler Ultrasound in Asymptomatic Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery Prior to Hospital Discharge: not recommended (Grade 1B Recommendation)

Isolated Lower Leg Injury (Distal to Knee) Patients

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Isolated Lower Leg Injury Requiring Immobilization: no prophylaxis is recommended (Grade 2C Recommendation)

Knee Arthroscopy Patients

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]

  • Knee Arthroscopy without Prior History of Venous Thromboembolism: no prophylaxis is recommended (Grade 2B Recommendation)

Treatment

General Comments

Strength of Clinical Indication for Anticoagulation in Lower Extremity Proximal vs Distal Deep Venous Thrombosis

General Goals of Anticoagulation in Venous Thromboembolism

Prevention of Early Complications of Venous Thromboembolism

Prevention of Late Complications of Venous Thromboembolism

Risk Stratification for Anticoagulation-Associated Hemorrhage (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) (Chest, 2016) [MEDLINE]

Risk Factors for Anticoagulation-Associated Hemorrhage

Absolute Risk of Major Hemorrhage

Clinical Features Which May Influence the Choice of Specific Initial/Long-Term Anticoagulants (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) (Chest, 2016) [MEDLINE]

Initial Treatment of Venous Thromboembolism

Parenteral Anticoagulation

Long-Term Treatment of Venous Thromboembolism without Cancer (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Recommended Agents

Long-Term Treatment of Venous Thromboembolism with Cancer (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Recommended Agents

Specific Duration of Anticoagulation (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Specific Treatment of Acute Pulmonary Embolism with Hypotension

Rationale

Agents

Absolute Contraindications to Systemic Thrombolytic Therapy (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]

Relative Contraindications to Systemic Thrombolytic Therapy (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]

Clinical Efficacy of Systemic Thrombolysis in Acute Pulmonary Embolism

Clinical Efficacy of Catheter-Directed Thrombolysis in Acute Pulmonary Embolism

Recommendations (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Specific Treatment of Acute Subsegmental Pulmonary Embolism

Rationale/Background

Recommendations (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Specific Treatment of Low-Risk Acute Pulmonary Embolism

Criteria

Recommendations (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Specific Treatment of Recurrent Venous Thromboembolism While on Anticoagulation (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) (Chest, 2016) [MEDLINE]

Rationale

Risk Factors for Recurrent Venous Thromboembolism

Recommendations (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Specific Use of Aspirin for Extended Treatment of Venous Thromboembolism

Recommendations (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Inferior Vena Cava (IVC) Filter Placement (see Inferior Vena Cava Filter)

Historical Perspective

Indications for Inferior Vena Cava (IVC) Filter

Technique

Clinical Efficacy

Recommendations (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) [MEDLINE]

Specific Treatment of Lower Extremity Deep Venous Thrombosis (DVT)

Outpatient vs Inpatient Therapy

Ambulation

Graduated Compression Stockings

Presence of Free-Floating Thrombus in Deep Venous Thrombosis

Catheter-Directed Thrombolysis of Acute Lower Extremity Deep Venous Thrombosis

Treatment of Isolated Distal (Calf) Deep Venous Thrombosis (Chest Antithrombotic Therapy for Thromboembolic Disease 2016 Guidelines) (Chest, 2016) [MEDLINE]

Specific Treatment of Upper Extremity Deep Venous Thrombosis

Anticoagulation

Catheter-Directed Thrombolysis of Upper Extremity Deep Venous Thrombosis Which Involves Axillary or More Proximal Veins


References

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines 2012

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines 2016

General

Risk Factors

Diagnosis

Clinical

Prophylaxis

Upper Extremity Deep Venous Thrombosis (DVT)

Treatment

General

Inferior Vena Cava Filter (see Inferior Vena Cava Filter)

Embolectomy

Thrombolytics

Catheter-Directed Thrombolysis