Thrombophilias: an overview
Thrombophilias are inherited or acquired hypercoagulable states that predispose to venous, and in some acquired conditions arterial, thrombosis. Testing is selective and deferred until the patient is off anticoagulation and remote from acute clot, because acute thrombosis, heparin, warfarin, and estrogen all distort results, and most results do not change acute management except in antiphospholipid syndrome.
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What this article covers
- Overview
Definition: thrombophilias are inherited or acquired hemostatic abnormalities that shift the coagulation-fibrinolysis balance toward clotting, raising VTE risk and, for a smaller set of acquired conditions, arterial thrombosis risk.
- Epidemiology
Factor V Leiden is the most common inherited thrombophilia, present in about 5% of White individuals as heterozygotes and under 1% as homozygotes; rare in other ethnic groups.
- Risk factors
Prior VTE: the strongest predictor of a subsequent event, regardless of whether a thrombophilia is identified.
- Pathophysiology
Inherited thrombophilias impair the natural anticoagulant system: factor V Leiden makes factor V resistant to inactivation by activated protein C, so procoagulant activity continues unchecked…
- Clinical features
Unprovoked or recurrent VTE without a clear precipitant is the leading clue to underlying thrombophilia.
- Differential diagnosis
Malignancy-associated (Trousseau) thrombosis: VTE as the presenting feature of occult cancer, especially pancreatic, ovarian, or hepatobiliary; age-appropriate screening, not extensive workup, since…
- Diagnosis
There is no single confirmatory "thrombophilia" test; the diagnosis is made by identifying a specific defect through selective, targeted testing, not routine testing of every VTE patient.
- Management
Treat the acute VTE with anticoagulation regardless of thrombophilia status; an inherited thrombophilia does not change acute treatment.
- Complications
Recurrent VTE: the dominant risk, especially with antiphospholipid syndrome, antithrombin deficiency, and unprovoked or cancer-associated events.
- Prognosis
Most heterozygous carriers stay asymptomatic; factor V Leiden confers only a fourfold to eightfold increase in first VTE risk and does not clearly raise recurrence risk.
- Prevention
Risk-stratify hospitalized and surgical patients with a validated tool (Caprini score) and give pharmacologic prophylaxis, for example enoxaparin 40 mg SC once daily, unless contraindicated…
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Related articles
- Factor V Leiden
Factor V Leiden is the most common inherited thrombophilia, a point mutation that makes factor V resistant to inactivation by activated protein C and raises venous thromboembolism risk, most strongly when combined with estrogen, pregnancy, surgery, or immobility. Diagnosis is an activated protein C resistance assay followed by confirmatory factor V Leiden DNA testing, and management is standard anticoagulation for an actual thrombotic event, not for the mutation alone.
- Antiphospholipid syndrome
Antiphospholipid syndrome is an acquired autoimmune thrombophilia in which antiphospholipid antibodies cause recurrent venous and arterial thrombosis and pregnancy morbidity, paradoxically prolonging the aPTT in vitro while promoting clotting in vivo. Diagnosis requires a qualifying clinical event plus a laboratory antibody confirmed positive on two occasions at least 12 weeks apart, and thrombotic disease is treated with indefinite warfarin rather than a DOAC.
- Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria is an acquired clonal stem cell disorder caused by a somatic PIGA mutation that leaves blood cells unprotected from complement, producing intravascular hemolysis, unusual-site venous thrombosis, and cytopenias. Diagnosis rests on flow cytometry showing loss of the GPI-anchored proteins CD55 and CD59, and eculizumab or ravulizumab is used to block terminal complement and reduce both hemolysis and thrombotic risk, while allogeneic stem cell transplant remains the only cure.