• Deep vein thrombosis of lower extremities with or without pulmonary embolism most common presentation
  • Atypical site increases likelihood of underlying hypercoagulable state
• Common triggers of thrombosis
  • Surgery
  • Trauma
  • Pregnancy
  • Malignancy
  • Prolonged immobilization
  • Infection
• Mean age at first thrombosis 35–40 yr in inherited hypercoagulable states
• Recurrent thrombosis suggests hypercoagulable state (inherited or acquired)
• Thrombosis in patient who has had previous pregnancies or surgeries (especially orthopedic procedures) without thrombotic complications suggests acquired hypercoagulable state
• Documented venous thromboembolism before 50 yr of age in a first-degree relative strongly suggests hereditary thrombotic disorder
• Spontaneous, idiopathic thrombosis, especially in a younger person, strongly suggests hereditary hypercoagulable state
• Relative risk of venous thrombosis and frequency of hypercoagulable states
  • High risk
    • Antithrombin deficiency (1%–2%)
    • Protein C deficiency (3%–4%)
    • Protein S deficiency (2%–3%)
  • Modest risk
    • Factor V Leiden (20%–25%)
    • Prothrombin mutation 20210A (10%)
    • Hyperhomocysteinemia (10%)
    • Oral contraceptive use (NA)
  • Combination of risk factors may have synergistic effect in increasing thrombosis risk

For mild to moderate DVT of the lower extremities with an obvious provoking factor, a limited workup is appropriate. An extensive workup is generally warranted if the likelihood of a hypercoagulable state is high.

Venous Thrombosis

• Resistance to protein C/factor V Leiden
  • Factor V Leiden (genetic test)
  • Clotting assay (unnecessary if factor V Leiden test is positive)
• Prothrombin mutation 20210A (genetic test)
• Antithrombin deficiency (functional assay)
• Protein C deficiency (functional assay)
• Protein S deficiency
  • Functional assay
  • Antigenic assay for free protein S
• Postpone measurement of antithrombin, protein C, and protein S until resolution of acute thrombotic episode (e.g., ≥ 4 wk after termination of oral anticoagulation therapy)

Arterial Thrombosis

• Antibodies associated with heparin-induced thrombocytopenia (in appropriate clinical settings)
• Chronic disseminated intravascular coagulation (in appropriate clinical settings)
• Lipoprotein(a)

Venous and/or Arterial Thrombosis

• Homocysteine
  • Fasting level
• Antiphospholipid antibody
  • Clotting assays for lupuslike anticoagulant
  • ELISA for anticardiolipin antibodies IgG and IgM
• Dysfibrinogenemia (if inherited hypercoagulable state is strongly suspected)
  • Functional assay for fibrinogen level
  • Thrombin time, reptilase time

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Prophylaxis for Venous Thromboembolism with Underlying Risk Factors

• Warfarin: INR 2.0–3.0
  • Cost/mo: $13.99–$23.55 (based on 1–10 mg q.d.)

High Risk

Lifelong oral anticoagulation therapy

• Recurrent idiopathic thrombosis
• One life-threatening thrombosis
• One spontaneous thrombosis at an unusual site (e.g., mesenteric or cerebral thrombosis)
• One spontaneous thrombosis associated with antiphospholipid antibody syndrome
• One thrombosis with two permanent risk factors
• One thrombosis with Trousseau factor

Medium Risk

6 mo of oral anticoagulation therapy after first episode of thrombosis; vigorous prophylaxis in high-risk situations

• One thrombosis with one permanent risk factor (except Trousseau syndrome and antiphospholipid antibody syndrome)
• Idiopathic thrombosis with no identifiable risk factor

Low Risk

3 mo of oral anticoagulation therapy after first episode of thrombosis; vigorous prophylaxis in high-risk situations

• One thrombosis with reversible risk factor

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Best References

Bauer KA: J Thromb Haemost 1:1429, 2003

Euro-Phospholipid Project Group: Arthritis Rheum 46:1019, 2002

Kearon C, et al: N Engl J Med 349:631, 2003

The author has no commercial relationships with manufacturers of products or providers of services discussed in this module.

November 2005