Thrombophilia
Definition
A predisposition to thrombosis (abnormal blood clot formation) due to inherited and/or acquired abnormalities of the coagulation system.
Aetiology
Inherited causes: [Ref]
- Factor V Leiden mutation (→ resistance to activated protein C) – most common
- Prothrombin gene mutation – 2nd most common
- Deficiencies in other coagulation inhibitors
- Antithrombin
- Protein C
- Protein S
Acquired causes: [Ref]
- Antiphospholipid syndrome – most common (see the Antiphospholipid Syndrome (APS) article for more information)
- Other acquired causes
- Acquired deficiency of coagulation inhibitors (e.g. hepatic impairment, sepsis)
- Myeloproliferative syndromes
- Triggering factors
- Malignancy
- Hormonal factors (e.g. COCP, HRT, pregnancy, puerperium)
- Surgery, trauma, immobilisation
Factor V Leiden mutation is the most common inherited cause of thrombophilia, while antiphospholipid syndrome is the most common acquired cause of thrombophilia.
Clinical Manifestation
The most frequent clinical presentation across most types of thrombophilia is VTE, which primarily manifests as: [Ref]
- DVT
- PE
Also see the Antiphospholipid Syndrome (APS) article.
When to Suspect Thrombophilia
Thrombophilia should be suspected in patients who exhibit a predisposition to VTE or an increased risk of recurrence.
One should suspect an underlying thrombophilic disorder in the following scenarios: [Ref]
- Young age with VTE
- First episode <40 y/o
- Unprovoked VTE in <60 y/o
- Recurrent VTE (regardless of whether other risk factors are present)
- VTE with minor triggers (e.g. pregnancy or oestrogen therapy being the sole identified risk factor)
- Unusual site VTE (e.g. mesenteric, hepatic, renal, portal, cerebral venous sinuses)
- Recurrent superficial thrombophlebitis (esp. in the absence of varicose veins)
Investigation and Diagnosis
Before screening for underlying thrombophilia, confirm the thrombotic event with objective tests (e.g. ultrasound, CTPA).
See the Venous Thromboembolism (DVT and PE) article for more information.
Main tests for a thrombophilia screen: [Ref]
| General coagulation profile |
|
| Natural coagulation inhibitors | Functional assays for:
|
| Hereditary genetic testing | Genetic testing for:
|
| Antiphospholipid syndrome screening | Test for:
See the Antiphospholipid Syndrome (APS) article for details on diagnosing antiphospholipid syndrome |
Management Principles
Key management principles: [Ref]
- Duration of anticoagulation after a thrombotic event depends on the risk profile and severity of the thrombophilia
- Low-risk profiles → typically 3–6 months anticoagulation
- High-risk profiles (e.g. homozygous Factor V Leiden, combined genetic defects) → may require prolonged / indefinite anticoagulation
- Thromboprophylaxis (high-risk settings)
- High-risk patients (e.g. surgery, hospitalisation, immobilisation) may require combined prophylaxis
- Pharmacological (e.g. heparin) – to reduce hypercoagulability
- Mechanical (e.g. intermittent pneumatic compression) – to reduce venous stasis
- High-risk patients (e.g. surgery, hospitalisation, immobilisation) may require combined prophylaxis
Note the following:
- Management of thrombophilia is specialist-led
- Treatment is individualised and depends on the underlying cause
- Antiphospholipid syndrome has specific management considerations and is important for exams — see the Antiphospholipid Syndrome (APS) article for further details