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
Definition
- Recurrent thrombosis due to either hereditary or acquired hypercoagulable risk factors
- Pathophysiology: excessive clotting in combination with vascular inflammation, involving one or more elements
- Endothelial injury
- Decreased blood flow
- Inherited or acquired imbalance between procoagulant and anticoagulant factors
Key Clinical Features
- 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
Differential Diagnosis
Inherited Hypercoagulable States
Acquired Hypercoagulable States
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
- 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
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
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