- Clinical science
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 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, endothelial damage) may be involved. Hypercoagulability may be acquired or inherited and can affect
The etiology of thrombophilia can be classified into two categories:
Thrombophilia is characterized by recurrent thromboembolism.
- Venous thromboembolism (most common): blood clots that form within the venous vascular system, dislodge, and travel to a distant location
- Arterial thromboembolism: blood clots that form within the arterial vascular system, dislodge, and travel to a distant location
- The hereditary thrombophilias below follow an autosomal dominant inheritance pattern, with the exception of hyperhomocysteinemia.
|Defect||Pathophysiology||Prevalence in general population|
Activated protein C resistance (APC-R)
| ||Heterozygosity: ∼ 5%|
|Homozygosity: < 1%|
|Elevated factor VIII||∼ 5%|
|Prothrombin mutation||∼ 3%|
|Protein S deficiency|| ||∼ 1%|
|Protein C deficiency|| |
|Antithrombin III deficiency||∼ 0.1%|
| || |
( or (
|Advanced Age|| |
- A family history of thromboembolism should raise suspicion of a hereditary etiology.
- Inquire about acquired causes and risk factors (e.g., medications, obstetric history, trauma).
- : antiphospholipid antibody syndrome) (prolonged in
- : elevated in malignancy or lupus
- Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin, beta2-glycoprotein I antibody)
- : testscomplete blood count (thrombocytopenia with heparin use), serotonin release assay (positive), antiplatelet factor 4 antibody (positive)
- 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 embolus 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