Hypercoagulable State

Lawrence L. K. Leung, M.D. Stanford University School of Medicine

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References


Key Clinical Features

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Differential Diagnosis

Inherited Hypercoagulable States

Acquired Hypercoagulable States

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Best Tests

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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Best Therapy

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

    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