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]
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
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]
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]
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]
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)
There is a High (6.3%) Risk of Venous Thromboembolism in Hospitalized Liver Disease Patients, Despite Abnormal Coagulation Parameters (Chest, 2010) [MEDLINE]
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]
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%)
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
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
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)
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]
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]
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]
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]
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]
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]
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]
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]
