Etiology
The etiology of thrombophilia can be classified into two categories:
Hereditary | Acquired |
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References:[1]
Clinical features
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
- Usually, an acute event that results in ischemic tissue damage (e.g., stroke, acute mesenteric ischemia, acute limb ischemia, acute coronary syndrome, pulmonary infarction)
References:[2][3]
Hereditary thrombophilia
- 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) Factor V Leiden |
| Heterozygosity: ∼ 5% |
Homozygosity: < 1% | ||
Elevated factor VIII |
| ∼ 5% |
Prothrombin mutation |
| ∼ 3% |
Protein S deficiency |
| ∼ 1% |
Protein C deficiency | < 1% | |
Antithrombin III deficiency |
| ∼ 0.1% |
Hyperhomocysteinemia |
| ∼ 5–7% |
References:[4][5][6][7][8]
Acquired thrombophilia
Etiology | Pathophysiology | |
---|---|---|
Surgery |
| |
Trauma |
| |
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Immobilization |
| |
Smoking |
| |
Obesity |
| |
| ||
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Oral contraceptive pills (OCPs) or hormone replacement therapy (HRT) |
| |
Heparin-induced thrombophilia |
| |
Pregnancy |
| |
Advanced age |
|
References:[3][9][10][11]
Diagnostics
-
History
- 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).
-
Laboratory tests
- Coagulation studies: active partial thromboplastin time (prolonged in antiphospholipid antibody syndrome)
- ESR: elevated in malignancy or lupus
- Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin, beta2-glycoprotein I antibody)
- Heparin-induced thrombocytopenia tests: complete blood count (thrombocytopenia with heparin use), serotonin release assay (positive), antiplatelet factor 4 antibody (positive)
- Hypercoagulability panel: APC resistance/factor V Leiden assay, prothrombin gene molecular analysis, protein C and S levels, antithrombin-heparin cofactor assay
- Imaging: consider CT scan if a malignancy is suspected
References:[2]
Treatment
Approach
-
Anticoagulant administration (therapeutic heparin bridged to warfarin): for pulmonary embolism or deep vein thrombosis
- 1st episode: 3 months
- 2nd episode: minimum of 6 months
- > 3 events: lifetime anticoagulation
- Consider an inferior vena cava filter if anticoagulant therapy is contraindicated.
-
Reduce risk factors
- Avoid oral contraceptive pills; : patients with factor V Leiden; women > 35 years old who smoke
- Smoking cessation
- Weight loss
Special considerations
- Avoid anticoagulation in trauma, hemorrhage, and severe hypertension.
- Heparin is contraindicated in patients with heparin-induced thrombocytopenia type II. Argatroban or lepirudin should be prescribed instead.
- Heparin is less effective in antithrombin III deficiency 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!
References:[1][12][13]
Prevention
Consider prophylaxis in the following high-risk groups:
- Postoperative patients
- Prolonged immobilization or hospitalization
- Malignancy
- Orthopedic conditions