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# Inherited thrombophilia

Inherited gene changes that make blood clot too easily, raising the risk of deep vein thrombosis and pulmonary embolism, often at a young age.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Femoral vein](https://durgical.com/en/anatomy/femoral-vein/)
- [Great saphenous vein](https://durgical.com/en/anatomy/great-saphenous-vein/)
- [Popliteal vein](https://durgical.com/en/anatomy/popliteal-vein/)
- [Deep femoral vein](https://durgical.com/en/anatomy/deep-femoral-vein/)
- [Small saphenous vein](https://durgical.com/en/anatomy/small-saphenous-vein/)
- [Pulmonary arteries](https://durgical.com/en/anatomy/right-pulmonary-artery/)
- [Portal vein](https://durgical.com/en/anatomy/hepatic-portal-vein/)

## In the clinical exam

- [Signs of deep vein thrombosis: Homans and the Wells score](https://durgical.com/en/clinical-exam/signs-of-deep-vein-thrombosis-homans-and-the-wells-score/)

## Why it happens

- [Thrombosis and Virchow's triad](https://durgical.com/en/general-pathology/thrombosis-and-virchow-s-triad/)
- [Hypercoagulable states: inherited and acquired](https://durgical.com/en/general-pathology/hypercoagulable-states-inherited-and-acquired/)
- [Fibrinolysis and natural anticoagulants](https://durgical.com/en/physiology/fibrinolysis-and-natural-anticoagulants/)
- [The coagulation cascade](https://durgical.com/en/physiology/the-coagulation-cascade/)

## What it is

A group of inherited conditions that increase the tendency to form venous blood clots, either by making procoagulant factors resistant or more abundant (factor V Leiden, prothrombin G20210A) or by reducing natural anticoagulants (antithrombin, protein C, protein S). Antiphospholipid syndrome is an acquired thrombophilia and is covered separately.

## Who gets it

Factor V Leiden is the most common inherited thrombophilia in people of European ancestry (heterozygous in about 3 to 8%) and the prothrombin G20210A variant is second. Both are less frequent in Indigenous and African-descended populations; Latin American studies show intermediate frequencies reflecting mixed ancestry. Antithrombin, protein C and protein S deficiencies are rare but carry a higher risk.

## Causes

- Factor V Leiden: a point mutation (R506Q) that makes factor V resistant to activated protein C
- Prothrombin G20210A: a variant that raises prothrombin levels
- Antithrombin deficiency
- Protein C deficiency
- Protein S deficiency
- Usually autosomal dominant; homozygous or combined defects carry a much higher risk

## Risk factors

- Family history of venous thrombosis, especially in young relatives
- Added acquired triggers: surgery, trauma, immobility, cancer, long travel
- Oestrogen-containing contraceptives and hormone therapy
- Pregnancy and the postpartum period
- Obesity and older age

## Pathophysiology

Normal clotting is balanced by natural anticoagulants. Activated protein C, with its cofactor protein S, inactivates factors Va and VIIIa; antithrombin neutralises thrombin and factor Xa. Factor V Leiden resists this inactivation (activated protein C resistance), the prothrombin variant increases thrombin generation, and deficiencies of antithrombin, protein C or S remove brakes. Clots form mainly in the deep veins of the legs, but also in unusual sites (cerebral, portal, mesenteric or [hepatic veins](https://durgical.com/en/anatomy/hepatic-veins/)). Protein C deficiency explains warfarin-induced skin necrosis, and antithrombin deficiency can cause resistance to heparin.

## Classification

- Gain of function: factor V Leiden, prothrombin G20210A (common, milder risk)
- Loss of function: antithrombin, protein C and protein S deficiencies (rare, higher risk)
- Heterozygous versus homozygous or combined defects
- Distinguish from acquired thrombophilias: antiphospholipid syndrome, cancer, nephrotic syndrome, PNH, myeloproliferative neoplasms

## Symptoms and signs

- Many carriers never have a clot
- Painful, swollen, warm leg from deep vein thrombosis
- Sudden breathlessness, chest pain or haemoptysis from pulmonary embolism
- Severe headache or seizures from cerebral venous thrombosis
- Recurrent pregnancy loss or placental complications in some women
- Purpura fulminans in newborns with homozygous protein C deficiency

## Red flags

- Signs of pulmonary embolism: sudden dyspnoea, chest pain, syncope, hypotension
- Thrombosis at unusual sites or before age 50 without a clear trigger
- Recurrent thrombosis despite anticoagulation
- Painful dark skin lesions after starting warfarin (skin necrosis)

## Diagnosis

**Clinical**
Suspect it with venous thrombosis at a young age, a weak or absent trigger, unusual sites, recurrence or a strong family history. Testing does not change acute treatment, and routine testing after a first provoked clot is not recommended.

**Tests**
Genetic tests for factor V Leiden (or activated protein C resistance assay) and prothrombin G20210A, which are reliable at any time; functional levels of antithrombin, protein C and protein S, which are best measured away from the acute clot and off anticoagulants (heparin lowers antithrombin; warfarin lowers protein C and S; pregnancy and oestrogens lower protein S). Antiphospholipid antibodies to exclude the acquired form.

**Imaging**
Compression Doppler ultrasound for deep vein thrombosis; CT pulmonary angiography for pulmonary embolism; brain MR venography or CT venography for cerebral venous thrombosis.

## Differential diagnosis

- Antiphospholipid syndrome
- Cancer-associated thrombosis
- Myeloproliferative neoplasms (polycythaemia vera, essential thrombocythaemia)
- Paroxysmal nocturnal haemoglobinuria
- Heparin-induced thrombocytopenia
- Nephrotic syndrome and oestrogen-related thrombosis

## Goal of treatment

Treat each clot with standard anticoagulation, decide the duration by weighing recurrence against bleeding risk, and prevent clots in high-risk situations.

## Treatment

**Medical**
Acute venous thrombosis is treated as in anyone else: parenteral anticoagulation (low molecular weight heparin) followed by an oral anticoagulant (a direct oral anticoagulant or warfarin overlapped with heparin).

**Medical**
Long-term or indefinite anticoagulation is considered after unprovoked or recurrent clots and in high-risk defects (antithrombin deficiency, homozygous or combined defects); antithrombin concentrate in selected situations.

**Conservative**
Thromboprophylaxis during surgery, immobility, pregnancy and the postpartum period in affected carriers according to risk; avoid oestrogen-containing contraceptives in favour of non-oestrogen methods.

**Lifestyle**
Keep active, stay hydrated and move the legs on long trips, maintain a healthy weight and stop smoking.

**Follow-up**
Nursing priorities: monitor for bleeding on anticoagulation, INR when warfarin is used, platelet count on heparin, and teach recognition of leg and [chest](https://durgical.com/en/anatomy/region/chest/) symptoms; check [skin](https://durgical.com/en/anatomy/skin/) after starting warfarin in protein C deficiency.

## Complications

- Recurrent deep vein thrombosis
- Pulmonary embolism and chronic thromboembolic pulmonary hypertension
- Post-thrombotic syndrome
- Pregnancy complications (pregnancy loss, preeclampsia, placental abruption) in some women
- Warfarin-induced skin necrosis
- Bleeding from long-term anticoagulation

## Prognosis

Most heterozygous carriers of factor V Leiden or the prothrombin variant never develop a clot. Risk rises sharply with combined defects, homozygosity, antithrombin deficiency and added triggers such as pregnancy or oestrogen.

## Prevention

- Prophylaxis in high-risk situations, informed choice of contraception, and family counselling
- Screening of relatives only when the result would change management

## Test yourself

Think of the answer, then tap the question to see it.

## What is the most common inherited thrombophilia in people of European ancestry?

Factor V Leiden, which causes resistance to activated protein C.

## Which deficiency causes resistance to heparin?

Antithrombin deficiency, because heparin works by enhancing antithrombin.

## Which deficiency predisposes to skin necrosis when warfarin is started without heparin overlap?

Protein C deficiency.

## Why are protein C, protein S and antithrombin levels not measured during acute thrombosis and anticoagulation?

The clot and the anticoagulants lower their levels, giving falsely low results.

## Which contraceptive type should carriers of inherited thrombophilia avoid?

Combined oestrogen-containing contraceptives.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/inherited-thrombophilia/)

## Related conditions

- [Deep vein thrombosis](https://durgical.com/en/conditions/deep-vein-thrombosis/)
- [Pulmonary embolism](https://durgical.com/en/conditions/pulmonary-embolism/)
- [Cerebral venous sinus thrombosis](https://durgical.com/en/conditions/cerebral-venous-sinus-thrombosis/)
- [Portal vein thrombosis](https://durgical.com/en/conditions/portal-vein-thrombosis/)
- [Budd-Chiari syndrome](https://durgical.com/en/conditions/budd-chiari-syndrome/)
- [Miscarriage (early pregnancy loss)](https://durgical.com/en/conditions/miscarriage/)
- [Preeclampsia](https://durgical.com/en/conditions/preeclampsia/)
- [Heparin-induced thrombocytopenia](https://durgical.com/en/conditions/heparin-induced-thrombocytopenia/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Factor V Leiden thrombophilia](https://medlineplus.gov/genetics/condition/factor-v-leiden-thrombophilia/) (MedlinePlus (U.S. National Library of Medicine), 2023); [Prothrombin thrombophilia](https://medlineplus.gov/genetics/condition/prothrombin-thrombophilia/) (MedlinePlus (U.S. National Library of Medicine), 2025).

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Source: https://durgical.com/en/conditions/inherited-thrombophilia/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/inherited-thrombophilia/