- 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 (stasis, hypercoagulability, 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.
The etiology of thrombophilia can be classified into two categories:
Thrombophilia is characterized by recurrent thromboembolisms.
- Venous thromboembolism (most common): , .
- Arterial thromboembolism: spontaneous abortion, , and recurrent .
- The hereditary thrombophilias below follow an autosomal dominant inheritance pattern, with the exception of hyperhomocysteinemia.
- Very rare: hereditary plasminogen deficiency, dysfibrinogenemia
|Defect||Pathophysiology||Prevalence in general population||Risk of thromboembolism|
Activated protein C resistance (APC-R)
| ||Heterozygosity: ∼ 5%|| |
Heterozygosity: 8x higher
|Homozygosity: < 1%||Homozygosity: 80x higher|
|Elevated factor VIII|| ||∼ 5%||7x higher|
|Prothrombin mutation||∼ 3%|| Heterozygosity: 3x higher |
Homozygosity: 50x higher
|Protein S deficiency|| ||∼ 1%||10x higher|
|Protein C deficiency|| |
|Antithrombin III deficiency||∼ 0.1%||> 10x higher|
| || |
∼ 2x higher
|Etiology||Pathophysiology||Risk of thromboembolism|
|Surgery|| || |
Operative risk (OR):∼ 1.2x higher/hr of surgery
|Trauma|| || |
Lower extremity fracture OR: ∼ 1.9x higher
Head injury OR:∼ 1.2x higher
Ventilator days > 3OR: ∼ 8.08x higher
Major operative procedure OR: 1.5x higher
| || |
Cancer alone: ∼ 4.1x higher
Chemotherapy: ∼ 6.5x higher
| || |
∼ 1.9x higher
|Smoking|| || |
Only smoking: ∼ 1.3–3.3x higher
With OCPs: ∼ 8.8x higher
∼ 2.5x higher
| || |
Lupus anticoagulant OR: ∼ 5.6x higher
Anti-cardiolipin antibodies OR: ∼ 2.2x higher
∼ 1.7x higher
( or (
Combined OCP OR: ∼ 3.5x higher
HRT OR: ∼ 1.2x higher
∼ 30x higher
|Pregnancy|| || |
> 5x higher per hour of surgery
|Advanced Age|| || |
Increases exponentially with 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.
The risk of venous thromboembolism is reduced with administration of an anticoagulant (e.g., heparin) following surgery!
Consider prophylaxis in the following high-risk groups:
- Postoperative patients
- Prolonged immobilization or hospitalization
- Orthopedic conditions