AKT · Haematology/Bleeding & clottinglow yield

Thrombophilia & venous thrombosis

Hypercoagulable state — inherited (factor V Leiden, etc.) or acquired (antiphospholipid, malignancy)

Overview

An increased tendency to thrombosis from inherited or acquired hypercoagulability. Inherited: factor V Leiden (commonest — activated protein C resistance), prothrombin gene mutation, protein C/S and antithrombin deficiency. Acquired: antiphospholipid syndrome, malignancy, pregnancy/oestrogen, nephrotic syndrome, surgery/immobility. It matters when thrombosis is unprovoked, recurrent, at a young age, at an unusual site, or with recurrent miscarriage — prompting selective testing.

Recognise

Venous thromboembolism (DVT/PE), especially unprovoked, recurrent, young, with a family history, or at unusual sites (cerebral/splanchnic veins)
Antiphospholipid syndrome: arterial AND venous thrombosis + recurrent miscarriage; paradoxically a prolonged APTT (lupus anticoagulant); associated with SLE
Provoking factors to weigh: surgery, immobility, pregnancy/oestrogen, malignancy, nephrotic syndrome

Red flags

Unprovoked VTE → assess for occult malignancy; recurrent pregnancy loss/arterial+venous thrombosis → test for antiphospholipid syndrome
Massive/life-threatening thrombosis → treat as VTE emergency (cross-ref cardiovascular PE)

Differentials & how to tell them apart

Provoked VTEclear transient risk factor (surgery/immobility) — usually no thrombophilia testing needed

Antiphospholipid syndromearterial + venous thrombosis + miscarriage, prolonged APTT, SLE association — needs long-term anticoagulation (warfarin)

Malignancy-associated thrombosisunprovoked VTE may herald cancer — investigate

Investigations

Confirm the thrombosis (Doppler/CTPA — see cardiovascular). Thrombophilia testing is SELECTIVE (not routine): factor V Leiden/prothrombin gene, protein C/S, antithrombin (test off anticoagulation/away from acute event), and antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein); investigate for malignancy if unprovoked.

Management

Anticoagulate the thrombosis (DOAC; WARFARIN for antiphospholipid syndrome); selective thrombophilia testing

1Treat the thrombosis (anticoagulation; DOAC first-line for most VTE). Test for thrombophilia SELECTIVELY — unprovoked/recurrent/young/unusual-site thrombosis or recurrent miscarriage — not routinely, and not during the acute event/on anticoagulation.Gate: Antiphospholipid syndrome (arterial + venous thrombosis + miscarriage, lupus anticoagulant) needs WARFARIN, not a DOAC; unprovoked VTE warrants assessment for occult malignancy.
2Decide anticoagulation duration (provoked → 3 months; unprovoked/recurrent/high-risk → extended), address provoking factors and provide pregnancy thromboprophylaxis (LMWH).

Anticoagulation for the thrombosis — DOAC first-line for most VTE (see cardiovascular); duration depends on provoked vs unprovoked/recurrent

Antiphospholipid syndrome → WARFARIN (not a DOAC) — especially triple-positive/arterial APS; DOACs are less effective in APS

Extended/lifelong anticoagulation — for unprovoked/recurrent VTE or high-risk thrombophilia after weighing bleeding risk

Address provoking factors + thromboprophylaxis — oestrogen, pregnancy (LMWH), immobility, surgery

Key points

Unprovoked/recurrent/young/unusual-site thrombosis or recurrent miscarriage → think thrombophilia; test SELECTIVELY (off anticoagulation). Factor V Leiden is commonest (activated protein C resistance). Antiphospholipid syndrome = arterial + venous thrombosis + miscarriage + paradoxically prolonged APTT → WARFARIN, not a DOAC. Unprovoked VTE → look for cancer.

Monitor & prognosis

Anticoagulation/bleeding, recurrence; malignancy work-up for unprovoked VTE.

Good with appropriate anticoagulation; APS and high-risk thrombophilia need long-term therapy.

Source: BSH thrombophilia; cross-ref cardiovascular (DVT/PE), rheumatology (APS/SLE)