[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Hemodynamic disorders](https://durgical.com/en/general-pathology/#a-hemodynamics) › Hypercoagulable states: inherited and acquired

[General pathology](https://durgical.com/en/general-pathology/) · [Hemodynamic disorders](https://durgical.com/en/general-pathology/#a-hemodynamics)

# Hypercoagulable states: inherited and acquired

- Topic

Some people clot too easily because of an inherited gene or an acquired situation, such as cancer, pregnancy or certain antibodies.

Updated 2026-11-01

## Key points

- Factor V Leiden: factor V resists activated protein C; the commonest inherited thrombophilia in people of European ancestry.
- Protein C deficiency: risk of skin necrosis when warfarin is started.
- Antithrombin deficiency: heparin loses its effect; antithrombin is also lost in the urine in nephrotic syndrome.
- Antiphospholipid syndrome: arterial and venous thrombosis and pregnancy loss; the lupus anticoagulant prolongs the aPTT in vitro but causes thrombosis in vivo.
- Heparin-induced thrombocytopenia: antibodies to the heparin–platelet factor 4 complex activate platelets: falling platelets with thrombosis.
- Trousseau: migratory thrombophlebitis with mucin-producing adenocarcinomas, such as pancreatic cancer.

## What it is

Hypercoagulability (thrombophilia) is an increased tendency to form thrombi. The commonest inherited causes are factor V Leiden and the prothrombin G20210A variant; less common are antithrombin, protein C and protein S deficiencies. Acquired causes are far more common: immobility, surgery, cancer, pregnancy, estrogens, antiphospholipid syndrome and heparin-induced thrombocytopenia. Suspect an inherited cause in thrombosis that is young, recurrent, in unusual sites or runs in the family.

## Key facts

- Common acquired causes: immobilisation, surgery and trauma, cancer, pregnancy and the postpartum period, estrogen-containing contraceptives, smoking, obesity and older age.
- Pregnancy is prothrombotic: several clotting factors rise and the uterus compresses the pelvic veins.
- Antiphospholipid syndrome can give a falsely positive non-treponemal syphilis test.

## Causes of hypercoagulability to know

| Cause | Type | Mechanism | Clue |
| --- | --- | --- | --- |
| [Factor V Leiden](https://durgical.com/en/conditions/inherited-thrombophilia/) | Inherited | Factor V resistant to activated protein C | DVT in a young person with a family history |
| [Prothrombin G20210A variant](https://durgical.com/en/conditions/inherited-thrombophilia/) | Inherited | More circulating prothrombin | Venous thrombosis, also in unusual sites |
| Antithrombin deficiency | Inherited or acquired | Less inhibition of thrombin and factor Xa | Resistance to heparin |
| Protein C or S deficiency | Inherited or acquired | Factors Va and VIIIa are not inactivated | Skin necrosis with warfarin |
| Hyperhomocysteinemia | Inherited or acquired | Endothelial damage | Folate or B12 deficiency; homocystinuria |
| [Antiphospholipid syndrome](https://durgical.com/en/conditions/antiphospholipid-syndrome/) | Acquired | Antibodies to phospholipid-binding proteins | Arterial and venous thrombosis, recurrent miscarriage |
| [Heparin-induced thrombocytopenia](https://durgical.com/en/conditions/heparin-induced-thrombocytopenia/) | Acquired | Antibodies activate platelets | Platelets fall days after heparin is started |
| Cancer | Acquired | Tumour cells release tissue factor and mucins | Migratory thrombosis (Trousseau) |
| [Nephrotic syndrome](https://durgical.com/en/conditions/nephrotic-syndrome/) | Acquired | Urinary loss of antithrombin | Renal vein thrombosis |
| [Myeloproliferative neoplasms](https://durgical.com/en/conditions/polycythaemia-vera/) | Acquired | Hyperviscosity and abnormal platelets | Thrombosis in abdominal veins (Budd-Chiari) |

## In the lab

- Thrombophilia work-up: activated protein C resistance or genetic testing for factor V Leiden and prothrombin, antithrombin, protein C and S levels.
- Antiphospholipid syndrome: lupus anticoagulant, anticardiolipin and anti-β2 glycoprotein I antibodies, confirmed on two separate occasions.

## Memory aid

Leiden will not take the brake: factor V Leiden ignores protein C.

## Test yourself

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

## What is the defect in factor V Leiden?

A point mutation makes activated factor V resistant to inactivation by activated protein C.

## Why does nephrotic syndrome favour thrombosis?

Because antithrombin is lost in the urine and the liver makes more procoagulant factors.

## What laboratory paradox does the lupus anticoagulant show?

It prolongs the aPTT in the test tube, yet in the patient it causes thrombosis.

## What combination defines heparin-induced thrombocytopenia?

A falling platelet count together with arterial or venous thrombosis, days after heparin is started.

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## Related

- [Thrombosis and Virchow's triad](https://durgical.com/en/general-pathology/thrombosis-and-virchow-s-triad/)
- [Disseminated intravascular coagulation: how consumption causes both clots and bleeding](https://durgical.com/en/general-pathology/disseminated-intravascular-coagulation-how-consumption-causes-both-clots-and-ble/)
- [Paraneoplastic syndromes: the table to know](https://durgical.com/en/general-pathology/paraneoplastic-syndromes-the-table-to-know/)
- [Pulmonary thromboembolism: where it comes from and what it does](https://durgical.com/en/general-pathology/pulmonary-thromboembolism-where-it-comes-from-and-what-it-does/)

## Related conditions

- [Inherited thrombophilia](https://durgical.com/en/conditions/inherited-thrombophilia/)
- [Antiphospholipid syndrome](https://durgical.com/en/conditions/antiphospholipid-syndrome/)
- [Heparin-induced thrombocytopenia](https://durgical.com/en/conditions/heparin-induced-thrombocytopenia/)
- [Nephrotic syndrome](https://durgical.com/en/conditions/nephrotic-syndrome/)
- [Polycythaemia vera](https://durgical.com/en/conditions/polycythaemia-vera/)
- [Essential thrombocythaemia and primary myelofibrosis](https://durgical.com/en/conditions/essential-thrombocythaemia-and-primary-myelofibrosis/)
- [Sickle cell disease](https://durgical.com/en/conditions/sickle-cell-disease/)
- [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/)

## Elsewhere in DurgiPedia

- [Fibrinolysis and natural anticoagulants](https://durgical.com/en/physiology/fibrinolysis-and-natural-anticoagulants/)
- [The coagulation cascade](https://durgical.com/en/physiology/the-coagulation-cascade/)
- [Coagulation tests: PT/INR, aPTT and platelets](https://durgical.com/en/physiology/coagulation-tests-pt-inr-aptt-and-platelets/)

## In Pharmacology

- [Heparin](https://durgical.com/en/pharmacology/heparin/)
- [Warfarin](https://durgical.com/en/pharmacology/warfarin/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Blood Clots | Hypercoagulability | MedlinePlus](https://medlineplus.gov/bloodclots.html) (MedlinePlus, US National Library of Medicine, 2023); [Factor V Leiden thrombophilia](https://medlineplus.gov/genetics/condition/factor-v-leiden-thrombophilia/) (MedlinePlus Genetics, US National Library of Medicine, 2023); [Antiphospholipid syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/antiphospholipid-syndrome/) (MedlinePlus Genetics, US National Library of Medicine, 2022).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/hypercoagulable-states-inherited-and-acquired/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/hypercoagulable-states-inherited-and-acquired/