Thrombophilia screen or screening

Thrombophilia screening for VENOUS thrombosis:

Appropriate indications:

• patients < 40 years old with spontaneous venous thromboembolism (VTE) (1)
  • note that some state age of < 50 years of age
    • first episode of thrombosis in patient under 50 years of age with no obvious risk factor (2)
• family history of VTE in young patients (<40 years old), with a known defect
• patients < 60 years old with a history of VTE + family history (1st degree relative, or known thrombophilia defect in family) of VTE or thrombophilia
• patients < 60 years with unusual site of VTE (includes sagittal sinus, axillary, mesenteric, subclavian (2))
• history of recurrent miscarriage, preeclampsia, placental abruption, IUGR; or history of unexplained stillbirth
• skin necrosis following use of warfarin (2)
• neonatal thrombosis (2)

There is no indication to screen women before they start OCP or HRT unless any of the above risk factors are also present

Thrombophilia screen to include (1,2,3):

• FBC and clotting screen - Activated Protein C resistance
• protein C - Factor V Leiden (if APCR positive)
• protein S - prothrombin gene mutation
• antithrombin
• lupus anticoagulant - anticardiolipin antibodies

Timing of Screening:

• if related to thrombosis should be 4 weeks after completion of anticoagulation
• should not be on Heparin or Warfarin. Avoid testing in the acute phase of thrombosis as acute phase changes may be present
• pregnancy, oral contraceptives, HRT and cancer chemotherapy may also affect some tests
• avoid intercurrent severe illness
• factor V Leiden and Prothrombin mutation are PCR tests so can be carried out in patients on anticoagulants and in acute phase. However, other tests will also be required later to exclude dual pathology

Thrombophilia screening for ARTERIAL thrombosis:

Appropriate indications:

• arterial thrombosis (e.g. TIA. cerebral thrombosis, MI) in patient < 40 years
• severe migraine (limited to anticardiolipin antibodies and lupus anticoagulant)

Thrombophilia screen to include:

• lupus anticoagulant
• anticardiolipin antibodies
• homocysteine
• lipoprotein A (clinicians not to forget other risk factors: smoking, BP, lipids, diabetes etc)

Notes:

• NICE suggest with respect to thrombophilia screening (4):
  • do not offer thrombophilia testing to patients who are continuing anticoagulation treatment
  • consider testing for antiphospholipid antibodies in patients who have had unprovoked DVT or PE if it is planned to stop anticoagulation treatment
  • consider testing for hereditary thrombophilia in patients who have had unprovoked DVT or PE and who have a first-degree relative who has had DVT or PE if it is planned to stop anticoagulation treatment
  • do not offer thrombophilia testing to patients who have had provoked DVT or PE
  • do not routinely offer thrombophilia testing to first-degree relatives of people with a history of DVT or PE and thrombophilia

References:

1. University Hospitals Coventry and Warwickshire NHS Trust (2004). Thrombophilia screening guideline.
2. Frimley Park NHS Foundation Trust (2012). Thrombophilia Screening
3. Investigation and management of heritable thrombophilia, Britsh Committee for Standards in Haematology. British Journal of Haematology 2001; 114(3): 512-28
4. NICE. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. NICE guideline NG158. Published: 26 March 2020. Last updated: 02 August 2023