Thrombophilia
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Definition
Thrombophilia refers to a predisposition to venous thromboembolism (VTE) due to inherited or acquired prothrombotic factors.Causes
| Inherited | Acquired |
|---|---|
| • Factor V Leiden (most common) • Prothrombin gene mutation (G20210A) • Protein C deficiency • Protein S deficiency • Antithrombin deficiency (highest risk, but rare) | • Antiphospholipid syndrome (APS) • Malignancy • Pregnancy, oestrogen use • Myeloproliferative disorders • Nephrotic syndrome |
Classification of inherited thrombophilia
Inherited thrombophilia may be classed as type 1 or type 2 where:
- Type 1 defects are the result of a deficiency of anticoagulant proteins. These are usually more serious and more rare e.g. antithrombin III and protein C and S deficiencies. These are usually the result of a deficiency of anticoagulants.
- Type 2 defects are the result of producing dysfunctional anticoagulant proteins, this results in normal levels of said protein but overall effect is reduced, with resulting overproduction of clotting factors. Type 2 defects are more common and relatively mild i.e Factor V Leiden (heterozyous) and Prothrombin G20210A mutations.
| Inherited thrombophilia | Prevalance % | Relative risk of VTE |
|---|---|---|
| Factor V Leiden | 4-5% | heterozygotes 3-8 / homozygotes 50-80 |
| Prothrombin G20210a | 2.0% | 3 |
| Protein C deficiency | 0.2% (estimated) | 10-15 |
| Protein S deficiency | 0.03-0.13% (estimated) | 10 |
| Antithrombin deficiency | 0.02-0.06% | 25-50 |
| Dysfibrinogenaemia | rare | variable |
Clinical Features
Inherited causes:
- Recurrent VTE
- VTE at young age (<50)
- Family history
- VTE in unusual sites (e.g., portal, cerebral veins)
- VTE ± arterial thrombosis (APS)
- Pregnancy morbidity (Antiphospholipid syndrome (APS) is a recognised cause of recurrent miscarriage, IUGR & pre-eclampsia)
- Thrombosis with cancer, surgery, immobility
Investigation & screening
- Universal screening is not currently recommended
- Selective testing based on history is more cost-effective than universal screening.
- Avoid testing during acute events or while on anticoagulants
- In pregnant women, APS testing should be done outside pregnancy
Screening
Asymptomatic relatives of patients with type 2 thrombophilia's do not need investigation.
Asymptomatic relatives of patients with type 2 thrombophilia's do not need investigation.
Management
Anticoagulation for acute episodes, possibly long-term depending on risk (In APS warfarin is favoured over DOACs)Prophylaxis during high-risk periods e.g. surgery, immobility or pregnancy.
Avoid triggers such as oestrogen-containing contraception and HRT when thrombophilia is present.
Prognosis
- VTE risk depends on thrombophilia type plus patient-specific and environmental factors.
- Many with heritable thrombophilia never develop thrombosis
- Testing may cause anxiety & counseling is advised
Key Points
- Factor V Leiden is the most prevalent cause of congenital thrombophilia and if the condition is homozygous carries the highest relative VTE risk (see table)
- Recurrent miscarriage is associated with Antiphospholipid syndrome (APS)
- Patients with blood group O have a 2-4 fold reduction in relative risk of VTE than those with non O blood groups. Lower factor VIII and vWF in these patients is protective.
- Of note two or more conditions can coexist and carry very high relative risks
- Congenital (inherited) thrombophilias can be type 1 or type 2.