Haematology & Oncology

Thrombophilia

Thrombophilia is an inherited or acquired tendency to thrombosis. Testing is selective because most heritable results do not change anticoagulation decisions, whereas antiphospholipid syndrome can alter the choice of anticoagulant, pregnancy management and long-term follow-up.

In a nutshell

Thrombophilia is a predisposition to thrombosis, but a positive heritable result rarely determines anticoagulation alone. Test selectively. Antiphospholipid syndrome is the key acquired form: it requires a clinical event plus persistent antibodies and often needs a VKA-based long-term pathway, particularly when triple-positive or arterial disease is present.

Classic presentation

A person with an unprovoked or recurrent VTE and a strong family history, or a person with arterial thrombosis or recurrent pregnancy morbidity in whom APS is being considered.

Key points

Treat the acute VTE on its clinical merits; do not delay anticoagulation for a thrombophilia screen.
NICE advises against routine hereditary testing after provoked VTE, during continuing anticoagulation or in asymptomatic relatives.
APS requires a qualifying clinical event plus persistent relevant antibodies on repeat testing.
Triple-positive APS is a VKA pathway: NICE recommends LMWH with a VKA initially for confirmed proximal DVT or PE, and BSH recommends against starting a DOAC for venous thrombosis or secondary prevention.
Anticoagulants and acute thrombosis can distort thrombophilia assays; involve the specialist laboratory.
Pregnancy, puerperium, surgery and immobility need situation-specific prophylaxis and an obstetric-haematology plan.

First-line investigation

Review the VTE context and indication for testing; if APS is clinically relevant, request lupus anticoagulant, anticardiolipin and anti-beta-2-glycoprotein I with specialist interpretation.

Management

Treat the event and identify danger

Stabilise and anticoagulate suspected or confirmed DVT or PE through the NICE VTE pathway; escalate massive PE, limb-threatening thrombosis, recurrent thrombosis or suspected catastrophic APS urgently.^2,3,5

Decide whether testing can change management

Record provocation, recurrence, unusual site, family history, pregnancy or oestrogen exposure and bleeding risk before ordering a screen. Do not offer hereditary thrombophilia testing after provoked VTE or while continuing anticoagulation when the result cannot alter management.^2,1
Consider antiphospholipid antibodies after unprovoked VTE if stopping anticoagulation is being considered, or when arterial, obstetric or unusual clinical features make APS plausible; arrange specialist interpretation because anticoagulants can interfere.^2,3

Confirm or exclude clinically important APS

APS requires an objectively confirmed thrombotic or qualifying pregnancy event plus lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein I antibodies on at least two occasions at least 12 weeks apart; do not diagnose it from a single positive result.³
When a heritable screen is justified, test factor V Leiden, the prothrombin gene variant and natural anticoagulant activity with specialist timing and interpretation; a negative screen does not remove the clinical VTE risk.¹

Choose anticoagulation for APS, not just for the word thrombophilia

For confirmed triple-positive APS with proximal DVT or PE, use LMWH with a VKA for at least 5 days or until the INR is at least 2.0 on 2 consecutive readings, then continue the VKA; avoid initiating a DOAC for venous thrombosis or secondary prevention in triple-positive APS.^2,3,5
Manage arterial APS, recurrent thrombosis, catastrophic APS and pregnancy morbidity through specialist haematology, rheumatology and obstetric teams; do not extrapolate the uncomplicated VTE pathway.^3,6,7,8

Review recurrence, bleeding and high-risk periods

Review anticoagulation at least annually, including recurrence risk, bleeding, renal and hepatic function, adherence, interactions and patient preference. Use the appropriate NICE prophylaxis pathway for admission, surgery, immobility, pregnancy and puerperium.^2,7,5
Offer clear advice about pregnancy planning, contraception, travel, warning symptoms and family testing. Do not screen asymptomatic relatives routinely; offer testing only when a specialist can explain how the result would change care.^2,1,3

Exam traps

A prolonged APTT can occur with lupus anticoagulant and thrombosis; it does not imply protection from clotting.
Do not interpret low protein C, protein S or antithrombin during acute thrombosis or under interfering anticoagulation without specialist input.
A positive antiphospholipid antibody test is not APS without a compatible clinical event and persistent positivity.
Do not use a low-risk heritable result as a reason for indefinite anticoagulation after a provoked event.
Do not use a DOAC as the default in triple-positive or arterial APS.

Illustrations

Deep vein thrombosis of the right legClinical photograph showing unilateral swelling and erythema of the right lower leg from deep vein thrombosis, an important presentation in patients with inherited or acquired thrombophilia.James Heilman, MD, Wikimedia Commons · CC-BY-SA-3.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.