Hypercoagulable States

Etiology

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
Hyperlipidemia (see Hyperlipidemia)
- Epidemiology
  - 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]
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

Hyperfibrinogenemia
Leukostasis (See Leukostasis)
- Epidemiology
  - Occurs in Acute Leukemia (see Acute Myeloid Leukemia)
Multiple Myeloma (see Multiple Myeloma)
- Physiology
  - Due to Hypergammaglobulinemia
Sickle Cell Disease (see Sickle Cell Disease)
Waldenstrom’s Macroglobulinemia (see Waldenstrom’s Macroglobulinemia)
- Physiology
  - Due to Hypergammaglobulinemia

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

Chronic Kidney Disease (CKD) (Especially with Hemodialysis) (see Chronic Kidney Disease)
Nephrotic Syndrome (see Nephrotic Syndrome)
Renal Transplant (see Renal Transplant)

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
  - Erythropoietin (see Erythropoietin)
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)
- Epidemiology
  - Risk of Venous Thromboembolism is Higher in Multiple Myeloma Patients Who Receive Thalidomide or Lenalidomide (Especially in Combination with Dexamethasone or Chemotherapy) (Leukemia, 2008) [MEDLINE]
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)
- Epidemiology
  - Mixed Inherited and Acquired Hypercoagulable State
- Etiologic Factors
  - Genetic Factors: most commonly a thermolabile variant of methylene tetrahydrofolate reductase (MTHFR) with reduced enzymatic activity (T mutation) (see Methylenetetrahydrofolate Reductase (MTHFR) Gene Mutation)
  - Chronic Kidney Disease (CKD) (see Chronic Kidney Disease): due to decreased renal removal and impaired metabolism
  - Hypothyroidism (see Hypothyroidism)
  - Folate Deficiency (see Folate)
  - Vitamin B6 (Pyridoxine) Deficiency (see Vitamin B6)
  - Vitamin B12 Deficiency (see Vitamin B12)
  - Fibrates (see Fenofibrate)
  - Niacin (Nicotinic Acid) (see Niacin)
  - Metformin (see Metformin)
  - Methotrexate (see Methotrexate)
  - Tobacco Abuse (see Tobacco)
- Clinical
  - May Result in Both Venous and Arterial Thromboses
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]

Clinical Manifestations

Venous Thromboembolism

Deep Venous Thrombosis (DVT) (see Deep Venous Thrombosis)

xxxx

Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism)

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References

Etiology

Severe pulmonary embolism associated with air travel. N Engl J Med. 2001 Sep 13;345(11):779-83 [MEDLINE]
Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch Intern Med. 2002;162(10):1182 [MEDLINE]
Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation. 2008;117(1):93 [MEDLINE]
Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008 Feb;22(2):414-23. doi: 10.1038/sj.leu.2405062 [MEDLINE]
Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res. 2009;123(suppl 4):S11-S17 [MEDLINE]
APC resistance: biological basis and acquired influences. J Thromb Haemost. 2010 Mar;8(3):445-53 [MEDLINE]
Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax. 2012 Apr;67(4):328-33[MEDLINE]
Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874 [MEDLINE]
Thrombosis in systemic lupus erythematosus: role of impaired fibrinolysis. Semin Thromb Hemost. 2013 Jun;39(4):434-40. doi: 10.1055/s-0033-1334484 [MEDLINE]
Cancer-associated thrombosis: an overview. Clin Med Insights Oncol. 2014;8:129-137 [MEDLINE]
Systemic sclerosis increases the risks of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Rheumatology (Oxford). 2014;53(9):1639 [MEDLINE]
Travelers’ thrombosis. Aviat Space Environ Med. 2014 Feb;85(2):191-4 [MEDLINE]
A meta-analysis of the risk of venous thromboembolism in inflammatory rheumatic diseases. Arthritis Res Ther. 2014 Sep 25;16(5):435. doi: 10.1186/s13075-014-0435-y [MEDLINE]
Cancer-associated thrombosis: an overview. Clin Med Insights Oncol. 2014;8:129-137 [MEDLINE]
Pulmonary embolism and tuberculosis. Asian Cardiovasc Thorac Ann. 2014 May;22(4):487-90. doi: 10.1177/0218492313485071 [MEDLINE]
VTE incidence and risk factors in patients with severe sepsis and septic shock. Chest. 2015;148:1224–1230 [MEDLINE]
Vascular Complications of Varicella: Description of 4 Cases and a Review of Literature. Pediatr Infect Dis J. 2015 Nov;34(11):1256-9. doi: 10.1097/INF.0000000000000855 [MEDLINE]
Venous thromboembolic events in systemic vasculitis. Ann Rheum Dis. 2015 Mar;74(3):e27. doi: 10.1136/annrheumdis-2014-206849 [MEDLINE]
Microscopic polyangiitis: A little-known new risk factor of venous thrombosis. J Mal Vasc. 2015 Dec;40(6):406-7. doi: 10.1016/j.jmv.2015.07.106. Epub 2015 Aug 28 [MEDLINE]
The risk of deep venous thrombosis and pulmonary embolism in giant cell arteritis: a general population-based study. Ann Rheum Dis. 2016 Jan;75(1):148-54. doi: 10.1136/annrheumdis-2014-205665 [MEDLINE]
Risk of Pulmonary Embolism and Deep Venous Thrombosis in Systemic Sclerosis: A General Population-Based Study. Arthritis Care Res (Hoboken). 2016 Feb;68(2):246-53 [MEDLINE]
Deep Vein Thrombosis as Initial Manifestation of Whipple Disease. Case Rep Gastroenterol. 2016 Nov 7;10(3):640-645. eCollection 2016 Sep-Dec [MEDLINE]
Consider Behcet’s disease in young patients with deep vein thrombosis. Respir Med Case Rep. 2016 Apr 14;18:41-4. doi: 10.1016/j.rmcr.2016.04.002. eCollection 2016 [MEDLINE]
Portal Venous Thrombosis: Eosinophilic Vasculitis. J Clin Diagn Res. 2017 Mar;11(3):OD04-OD05. doi: 10.7860/JCDR/2017/25235.9575 [MEDLINE]
Cerebral venous sinus thrombosis in Behçet’s disease: a retrospective case-control study. Clin Rheumatol. 2017 Jun 14. doi: 10.1007/s10067-017-3718-2 [MEDLINE]
Behcet Disease Initially Presenting as Deep Venous Thrombosis: A Case Report. J Pediatr Hematol Oncol. 2017 Apr 21. doi: 10.1097/MPH.0000000000000830 [MEDLINE]
Clinical associations with venous thromboembolism in anti-neutrophil cytoplasm antibody-associated vasculitides. Rheumatology (Oxford). 2017 May 1;56(5):704-708. doi: 10.1093/rheumatology/kew465 [MEDLINE]
Venous thrombosis and relapses in patients with Behçet’s disease. Descriptive analysis from Spanish network of Behçet’s disease (REGEB cohort). Clin Exp Rheumatol. Nov-Dec 2018;36(6 Suppl 115):40-44 [MEDLINE]
Higher Dose of Tofacitinib for Rheumatoid Arthritis Poses Risks. JAMA. 2019 Apr 2;321(13):1245. doi: 10.1001/jama.2019.2986 [MEDLINE]
High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020 Jun;46(6):1089-1098. doi: 10.1007/s00134-020-06062-x [MEDLINE]
Racial disparities in cancer-associated thrombosis. Blood Adv. 2022;6(10):3167-3177. doi:10.1182/bloodadvances.2021006209 [MEDLINE]