Thromboembolism Risk Factors

Aka: Thromboembolism Risk Factors, Pulmonary Embolism Risk Factors, Deep Vein Thrombosis Risk Factors, VTE Risk, DVT Risk, PE Risk, Venous Thromboembolism Risk, Recurrent Thromboembolism Risk

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II. Epidemiology

  1. Patients with VTE and no risk Factors under age 40 years: 28%

III. Pathophysiology: Virchow's Triad

  1. VTE is caused by at least one of three dysfunctions
    1. Hypercoagulability
    2. Blood Flow alterations
    3. Endothelial injury or dysfunction

IV. Risk Factors: Venous Thromboembolism By Strength of Risk

  1. Strong Risk Factors (Odds Ratio >10)
    1. Hip Fracture (or leg Fracture)
    2. Total Hip Arthroplasty (THA)
    3. Total Knee Arthroplasty (TKA)
    4. Major general surgery (within last 3 months)
    5. Major Trauma (within last 3 months)
    6. Spinal Cord Injury
  2. Intermediate Risk Factors (Odds Ratio 2-9)
    1. Arthroscopic knee surgery
    2. Central venous catheters (e.g. femoral line)
    3. Active Cancer
    4. Chemotherapy
    5. Chronic Heart Failure
    6. Respiratory Failure
    7. Hormone Replacement Therapy
    8. Oral Contraceptives with Estrogen
    9. Malignancy
    10. Cerebrovascular Accident with Hemiplegia
    11. Pregnancy or postpartum
    12. Thrombophilia
    13. Prior Venous Thromboembolism
  3. Weak Risk Factors(Odds Ratio <2)
    1. Bed rest >3 days
    2. Car or air travel >8 hours (or other prolonged sitting)
    3. Advanced age
    4. Laparoscopic surgery
    5. Morbid Obesity (BMI >40)
    6. Varicose Veins
    7. Testosterone Replacement (esp. first 3 months of use)
    8. Male Gender
  4. References
    1. Anderson (2003) Circulation 107(23 suppl 1): 19-116 [PubMed]

V. Risk Factors: Initial Venous Thromboembolism by chronicity

  1. Major transient risks
    1. Hospitalization >3 days with limited mobility
    2. Hospitalization for COVID-19 Management
    3. Immobilization for >3 days
      1. Plaster cast immobilization
      2. Bed rest
    4. Surgery under general Anesthesia >30 minutes
    5. Trauma
  2. Minor transient risks
    1. Hospitalization <3 days
    2. Prolonged travel >2 hours (risk increases 18% for every 2 hours traveled)
      1. Highest risk with air travel >4 hours or car travel >12 hours within a 24 hours period
    3. Pregnancy
    4. Estrogen in Oral Contraceptives or other hormonal products or Testosterone Replacement
    5. Major risk factor preceding VTE by 1 to 3 months
  3. Chronic or Persistent Risks
    1. Collagen vascular disease (e.g. Systemic Lupus Erythematosus, Rheumatoid Arthritis)
    2. Antiphospholipid Antibody Syndrome
    3. Adult low body weight <110 pounds or <50 kg
    4. Adult high body weight > 264 lb (120 kg) or BMI >= 30 kg/m2
    5. Chronic immobilization
    6. Chronic infectious disease
    7. Inflammatory Bowel Disease
    8. Male gender
    9. Heart Failure
    10. Cancer
    11. Myeloproliferative disorders
    12. Nephrotic Syndrome
    13. Recurrent Pregnancy Loss

VI. Risk Factors: Recurrent Thromboembolism after stopping Anticoagulants (Relative Risk)

  1. Metastatic cancer (6-9)
    1. Stage 4 Prostate Cancer has the highest recurrence rates
  2. Factor VIII >200 IU/dl (6)
  3. Non-metastatic Cancer (3)
    1. Brain Cancer
    2. Myeloproliferative Disorders
    3. Ovarian Cancer
    4. Lung Cancer
    5. Non-rectal Gastrointestinal cancer
  4. Antiphospholipid Antibody Syndrome (2.5)
  5. D-Dimer increase after acute therapy completed (2.2)
  6. Persistent risk factors - see above (2)
  7. Idiopathic VTE (2)
  8. Protein C,Protein S and Antithrombin deficiency (1.8)
  9. Prothrombin mutation - G20210A (1.7)
  10. Homozygous for Factor V Leiden (1.6)
  11. Second VTE (1.5)
    1. Proximal DVT has a 4 fold higher risk of recurrence than distal DVT
    2. Central Pulmonary Embolism has higher risk of recurrence than peripheral PE
  12. Mild Hyperhomocysteinemia (0.9)
  13. Transient risk factors (0.5)
  14. Kearon (2008) Chest 133(6 suppl):454S [PubMed]

VII. Risk Factors: Venous Stasis

  1. Hospitalization (Relative Risk: 100)
  2. Prolonged immobility
  3. Long leg Fracture or other limb immobilization
  4. Paralysis
    1. Cerebrovascular Accident (CVA)
    2. Spinal Cord Injury
  5. Varicose Veins
    1. High risk for DVT in surgery without DVT Prophylaxis
  6. Obesity
  7. Cardiac Disease
    1. Congestive Heart Failure
    2. Atrial Fibrillation
    3. Myocardial Infarction
  8. May-Thurner Syndrome
    1. Compressed right iliac common artery (RICA) results in ileofemoral DVT
    2. Arterial variants of RICA predispose to compression
    3. Resulting RICA pressure against lumbar bony Vertebrae resulting in bony spur formation
    4. Spurs and RICA compress iliac veins, resulting in DVT (esp. Left ileofemoral DVT)
    5. More common in women (RR 2)
    6. Responsible for 2 to 5% of DVTs (esp. females in their teens and twenties)

VIII. Risk Factors: Hypercoagulable

  1. Hypercoagulable state
    1. See Thrombophilia
    2. Inherited cause found in up to one third of DVT cases
      1. Mateo (1997) Thromb Haemost 77:444-51 [PubMed]
  2. Prior Deep Vein Thrombosis (DVT)
  3. Medications
    1. Increased Estrogen
      1. Oral Contraceptive or Estrogen Replacement
      2. Pregnancy
      3. Tamoxifen (Nolvadex)
    2. Hydralazine
    3. Phenothiazines
    4. Procainamide
  4. Major Trauma
  5. Recent Surgery
  6. Systemic Lupus Erythematosus
    1. Associated with Antiphospholipid Antibody Syndrome
    2. Venous Thromboembolism is a major cause of mortality in SLE
  7. Cancer (responsible for 20% of pulmonary emboli, and PE may be the cancer's presenting finding)
    1. Colon Cancer
    2. Ovarian Cancer
    3. Multiple Myeloma
    4. Consider evaluation for occult cancer in DVT
  8. Chemotherapy
  9. Inflammatory Bowel Disease
  10. HIV Infection
    1. Associated with a 7% annual Incidence of DVT
    2. Primary Thrombophilia mechanism is via affects on Protein C and Protein S
    3. Opportunistic infection with associated endothelial damage also contributes to thrombosis risk
  11. Polycythemia
  12. Sickle Cell Anemia
  13. Nephrotic Syndrome
  14. History of thromboembolic disease
    1. Deep Venous Thrombosis
    2. Pulmonary Embolus
  15. Type A Blood

IX. Risk Factors: Intimal damage

  1. Local Trauma
  2. Surgery (Especially General and Orthopedic Surgery)
    1. General Anesthesia is an independent risk factor
    2. Consider DVT Prophylaxis
  3. Penetrating vessel injury
    1. Intravenous Drug Abuse
    2. Central Line Placement
      1. Especially femoral Central Line

X. References

  1. Heit (2002) Arch Intern Med 162:1245-8 [PubMed]
  2. Mount (2022) Am Fam Physician 105(4): 377-85 [PubMed]
  3. Wilbur (2012) Am Fam Physician 86(10):913-9 [PubMed]

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