Synopsis
Select inherited thrombophilia testing only when it can change care, interpret assays at a valid time, and base anticoagulation, family and pregnancy decisions on the whole recurrence risk rather than a genetic label alone.
- Do not order hereditary thrombophilia testing after a clearly provoked VTE or while a patient will continue anticoagulation regardless of the result; test only when a defined result can change care.
- NICE advises considering hereditary testing after unprovoked VTE when a first-degree relative has DVT or PE and stopping anticoagulation is being considered; consider APS testing separately.
- Core inherited defects are factor V Leiden, prothrombin G20210A and antithrombin, protein C and protein S deficiency; MTHFR variants and homocysteine panels are not routine thrombophilia tests.
- Factor V Leiden and prothrombin genotype are stable, but acute thrombosis, heparin, warfarin, DOACs, liver disease, nephrotic syndrome, pregnancy and oestrogen distort functional assays.
- Confirm a low antithrombin, protein C or protein S result on a later well-state sample and exclude acquired causes before diagnosing an inherited deficiency or testing relatives.
- Treat acute VTE by ordinary site-specific guidance. A thrombophilia result rarely changes the initial drug or intensity and must never delay therapeutic anticoagulation.
- At three months, base continuation on provoked versus unprovoked status, recurrence, bleeding risk, sex, site, persistent factors and preference; a common heterozygous variant alone does not mandate lifelong treatment.
- Pregnancy prophylaxis is risk-combination based: previous VTE, antithrombin deficiency, homozygous or combined traits, family history, weight and obstetric factors require haematology-obstetric planning.
Key red flags
Shock, syncope, severe hypoxaemia, chest pain or cardiac arrest with suspected PE requires immediate resuscitation and reperfusion assessment rather than hereditary testing.
Widespread neonatal skin necrosis or purpura fulminans suggests homozygous severe protein C or protein S deficiency and needs urgent protein replacement and specialist anticoagulation.
Warfarin-associated skin necrosis soon after initiation can reflect rapid protein C depletion, especially in an underlying deficiency, and requires immediate anticoagulation and haematology review.
Painful retiform skin necrosis shortly after VKA initiation can reflect rapid protein C decline and needs urgent treatment review.
Investigation priorities
Establish whether a result will alter anticoagulant duration, pregnancy, oestrogen or relative counselling.
Management branches
DVT, PE or unusual venous thrombosis is suspected or confirmed.
- Start the site-specific diagnostic and therapeutic anticoagulation pathway; do not postpone treatment for thrombophilia blood sampling.
- Document provoking factors, family history, pregnancy, oestrogen, cancer and prior events and obtain routine organ and bleeding baseline.
- Ask which result could alter later care and defer functional testing until interference has resolved and a stopping decision is genuine.