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Risk Factors for Venous Thromboembolism (VTE)

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Risk Factors for Venous Thromboembolism (VTE)
Acquired Risk Factors Established Inherited Risk Factors
  1. Malignancy-associated

  2. Antiphospholipid antibody syndrome

  3. Pregnancy-associated

  4. Estrogen therapy

  5. Immobilization

  6. Trauma

  7. Nephrotic syndrome

  8. Heparin-induced thrombocytopenia

  9. Myeloproliferative neoplasms

  10. Paroxysmal nocturnal hemoglobinuria

  11. Prolonged air travel

  12. Major surgery

  1. Antithrombin deficiency

  2. Protein C deficiency

  3. Protein S deficiency

  4. Factor V Leiden mutation

  5. Prothrombin G20210A mutation

  6. Dysfibrinogenemia (rare)

Some acquired risk factors may be transient

Evaluation of a Patient After a VTE: Routine Evaluation

  1. History and examination to identify acquired risk factors (see above). This should include obstetric history in women because recurrent second- or third-trimester fetal loss may suggest antiphospholipid antibody syndrome or hereditary thrombophilia

  2. Detailed family history with inquiry regarding female family members who have taken oral contraceptives or suffered any venous thrombotic events during pregnancy

  3. CBC and peripheral smear to evaluate for underlying disease (eg, myeloproliferative disorder such as essential thrombocythemia, polycythemia vera or microangiopathic hemolysis)

  4. Other laboratory tests as indicated (eg, antibody testing to evaluate for heparin-induced thrombocytopenia if applicable)

  5. Extensive screening for malignancy not recommended. Perform age-appropriate screening as indicated. Lower threshold to search for malignancy based on symptoms or signs, especially in older patients with a smoking history, recurrent or bilateral VTE

  6. Thrombophilia screen as outlined below for idiopathic deep vein thrombosis

Who should be tested for hereditary thrombophilia?


  • VTE at age <50 years with positive family history (first-degree relatives)

  • Cerebral venous thrombosis

  • Portal/mesenteric vein thrombosis (rule out myeloproliferative neoplasms such as polycythemia vera, essential thrombocythemia, and paroxysmal nocturnal hemoglobinuria)

  • Pregnancy loss (second and third trimester)


  • VTE in association with oral contraceptives/hormone replacement therapy or pregnancy

  • Patients >50 years with first spontaneous VTE


  • Arterial thrombosis (except for paradoxical emboli)

  • Asymptomatic patients with no personal or familial history of VTE

  • Women using oral contraceptives with no familial history of VTE

  • Venous thromboembolism in patients with active cancer

  • Elderly patients with postoperative venous thromboembolism

  • Retinal vein thrombosis

Laboratory Evaluation for Recurrent Arterial Thrombosis

  1. Only the presence of a lupus anticoagulant/elevated cardiolipin antibody levels are risk factors for arterial thrombosis; the hereditary thrombophilias are not risk factors

  2. Consider other disease states, including paroxysmal nocturnal hemoglobinuria, heparin-induced thrombocytopenia, occult malignancy, myeloproliferative disorders, and cocaine abuse

Acquired Risk Factors

1. Malignancy-Associated Thrombosis


  1. Accounts for approximately 20% of all cases of VTE

  2. In some prospective studies, the incidence of malignancy in the first year after diagnosis of an idiopathic VTE is >7%. However, trials have not demonstrated improved patient outcomes and cost-effectiveness of extensive screening beyond age-appropriate or symptom-directed cancer screening


  1. Etiology not clearly established

  2. May be related to tissue factor elaborated by tumor cells

Management of thrombosis:

  1. Acute thrombosis: Heparin or low-molecular-weight heparin (LMWH)

  2. Long-term therapy: Patients with cancer have a higher risk of recurrence than individuals who suffer an unprovoked VTE in the absence of cancer. Anticoagulate a minimum of 6 months and as long as ...

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