Genomics in general practice

Disease specific topics

Hereditary thrombophilia

Hereditary thrombophilia


Individuals who may benefit from genetic testing for hereditary thrombophilia include:

  • individuals with venous thromboembolism (VTE) <50 years of age without the following
    • major transient risk factor (eg surgery, immobility, trauma)
    • oestrogen provocation (eg pregnancy, prescribed oestrogens)
  • individuals with VTE <50 years of age in an unusual site (eg central nervous system, abdominal veins, upper limb)
  • pregnant women who have had a previous episode of VTE or who have a strong family history of VTE (≥2 family members). 

Routine genetic testing for hereditary thrombophilia in individuals without any of the above features is not recommended.

What do I need to know?

Individuals with hereditary thrombophilia have an increased tendency to develop blood clots.

There are a number of different types of hereditary thrombophilia conditions (Box 1). At least half of thrombotic episodes in individuals with hereditary thrombophilia occur during periods of increased risk, such as during pregnancy, immobilisation or surgery.

The risk of VTE in women taking a low-dose combined oral contraceptive (COC; <35 ug ethinyl oestradiol) is increased two to three times, compared with non-users. Despite this increase in risk, there is no indication for routine genetic screening of women prior to prescribing a COC.

Box 1. Major hereditary thrombophilia conditions

Group 1 conditions – Due to a defect or deficiency of an anticoagulant protein:

  • Antithrombin deficiency
  • Protein C deficiency
  • Protein S deficiency

Group 2 conditions – Due to genetic mutations that result in an increased tendency towards thrombosis:

  • Activated protein C resistance
  • Factor V Leiden
  • Prothrombin gene variant
  • Elevated levels of factors VIII, IX or XI

Other conditions:

  • Hyperhomocysteinaemia

The risk of thrombosis is higher for patients with Group 1 conditions than Group 2 conditions. Group 2 conditions occur approximately five times more frequently than Group 1 conditions.

Genetic testing

Testing practices for hereditary thrombophilia are variable across Australia, in part due a to lack of local evidence-based guidelines.

Factor V Leiden and prothrombin variant genetic testing is only available on the Medicare Benefits Schedule (MBS) if the patient has a:

  • personal history of VTE
  • family history of a diagnosed inherited thrombophilic condition

When should I refer?

Refer women with hereditary thrombophilia who are pregnant or thinking about pregnancy. Management of hereditary thrombophilia in pregnancy requires specialised risk assessment, and patients should be under the direction of a specialist haematologist, obstetric physician or obstetrician.

Other considerations

Patients diagnosed with hereditary thrombophilia should be encouraged to inform all first-degree relatives of increased risk; however, the benefit of cascade screening of relatives for group 2 genetic variants (see box) is uncertain.

Further reading

  • Ho WK, Hankey GJ, Eikelboom Should adult patients be routinely tested for heritable thrombophilia after an episode of venous thromboembolism? Med J Aust 2011;195(3):139–42.
  • Haematology Society of Australia and New Zealand and Choosing Wisely Tests, treatments and procedures clinicians and consumers should question. Sydney: NPS MedicineWise, 2016. [Accessed 6 September 2022].
  • National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. NICE guideline [NG158] March 2020. Accessed 10.3.22.
  • C Hotoleanu. Genetic Risk Factors in Venous Thromboembolism. Adv Exp Med Biol. 2017;906:253-272. doi: 10.1007/5584_2016_120. .
  • Bateson D, Butcher BE, Donovan C, et Risk of venous thromboembolism in women taking the combined oral contraceptive: A systematic review and meta-analysis. Aust Fam Physician 2016;45(1–2):59.
  • Department of Medicare benefits schedule book: Category 6. Canberra: DoH, 2017. [Accessed 6 September 2022].
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