General pathology · Hemodynamic disorders
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
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 | Inherited | Factor V resistant to activated protein C | DVT in a young person with a family history |
| Prothrombin G20210A variant | 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 | Acquired | Antibodies to phospholipid-binding proteins | Arterial and venous thrombosis, recurrent miscarriage |
| 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 | Acquired | Urinary loss of antithrombin | Renal vein thrombosis |
| Myeloproliferative neoplasms | 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.
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.
Related
- Thrombosis and Virchow's triad
- Disseminated intravascular coagulation: how consumption causes both clots and bleeding
- Paraneoplastic syndromes: the table to know
- Pulmonary thromboembolism: where it comes from and what it does
Related conditions
- Inherited thrombophilia
- Antiphospholipid syndrome
- Heparin-induced thrombocytopenia
- Nephrotic syndrome
- Polycythaemia vera
- Essential thrombocythaemia and primary myelofibrosis
- Sickle cell disease
- Deep vein thrombosis
- Pulmonary embolism
- Cerebral venous sinus thrombosis
Elsewhere in DurgiPedia
- Fibrinolysis and natural anticoagulants
- The coagulation cascade
- Coagulation tests: PT/INR, aPTT and platelets
In Pharmacology
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 (MedlinePlus, US National Library of Medicine, 2023); Factor V Leiden thrombophilia (MedlinePlus Genetics, US National Library of Medicine, 2023); Antiphospholipid syndrome: MedlinePlus Genetics (MedlinePlus Genetics, US National Library of Medicine, 2022).
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Representative model, for educational purposes only.