A hypercoagulable state, i.e., thrombophilia, is characterized by an increased predisposition to form blood clots. Depending on the etiology, one or more factors from endothelial damage) may be involved. Hypercoagulability may be acquired or inherited and can affect veins and/or arteries. The most common presentation is recurrent of the lower extremities and . Arterial involvement increases the risk of , , and spontaneous . Evaluation for hypercoagulability includes assessment of potential risk factors (e.g., immobilization, smoking, oral contraceptive use, and malignancy) and laboratory tests to assess anomalies of the clotting cascade (e.g., , ). Treatment is based on the underlying condition and typically includes a reduction of risk factors and/or the administration of anticoagulants.(stasis, hypercoagulability,
The etiology of thrombophilia can be classified into two categories:
Thrombophilia is characterized by recurrent thromboembolism.
- Venous thromboembolism (most common)
- Arterial thromboembolism
- The hereditary thrombophilias below follow an autosomal dominant inheritance pattern, with the exception of hyperhomocysteinemia.
- Very rare: hereditary plasminogen deficiency, dysfibrinogenemia
|Pathophysiology of hereditary thrombophilia |
|Defect||Pathophysiology||Prevalence in general population|
Activated protein C resistance (APC-R)
Factor V Leiden
| || |
|Elevated factor VIII|| |
|Prothrombin mutation|| |
Protein S deficiency
| || |
|Protein C deficiency|| |
|Antithrombin III deficiency|| || |
| || |
|Pathophysiology of acquired thrombophilia |
( or (
|Advanced age |
- antiphospholipid antibody syndrome): (prolonged in
- malignancy or lupus : elevated in
- Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin, beta2-glycoprotein I antibody)
- complete blood count (thrombocytopenia with heparin use), serotonin release assay (positive), antiplatelet factor 4 antibody (positive) tests:
- Hypercoagulability panel: gene molecular analysis, and S levels, antithrombin-heparin cofactor assay/ assay,
- Imaging: consider scan if a malignancy is suspected
Anticoagulant administration (therapeutic bridged to ): for pulmonary embolism or deep vein thrombosis
- 1st episode: 3 months
- 2nd episode: minimum of 6 months
- > 3 events: lifetime anticoagulation
- Consider an if anticoagulant therapy is contraindicated.
- Reduce risk factors
- Avoid anticoagulation in trauma, hemorrhage, and severe hypertension.
- Heparin is contraindicated in patients with . Argatroban or lepirudin should be prescribed instead.
- Heparin is less effective in and may require also antithrombin concentrate to be effective
- Administering warfarin to a person with protein C and S deficiencies can precipitate warfarin-induced skin necrosis.
Consider prophylaxis in the following high-risk groups:
- Postoperative patients
- Prolonged immobilization or hospitalization
- Orthopedic conditions