HNY Policy and Pathway Repository - North Yorkshire

Individuals who have an increased risk of developing a pathological thrombosis are described as having a thrombophilia. There are both inherited and acquired causes of thrombophilia. Low-risk thrombophilias such as the factor V Leiden mutation or the prothrombin G20210A mutation are common in the population (each ~3-5% population) and are weak risk factors for thrombosis. Rarer thrombophilias such as deficiencies of antithrombin, protein C or protein S (~0.1-0.2% population) are stronger risk factors for thrombosis.

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Requests for thrombophilia testing are most commonly encountered following an episode of venous thrombosis or if there is a family history of thrombosis or thrombophilia. Thrombophilia testing should only be performed if it will influence clinical management and should not be performed indiscriminately in these situations. Inherited thrombophilia testing is also not recommended following unprovoked, early (<50yr) arterial thrombosis (consider anti-phospholipid syndrome +/- exclusion of a myeloproliferative disorder or PHN if clinical suspicion).

It should be noted that results are unlikely to influence the intensity or duration of anticoagulation following VTE and are only weakly related to the risk of recurrence. Even in the absence of an identifiable thrombophilia, NICE currently advise to consider continuing anticoagulation beyond 3 months (6 months for people with active cancer) after an unprovoked DVT or PE. Base this decision on the balance between the person's risk of venous thromboembolism recurrence (which is only weakly influenced by common, low risk thrombophilia) and their risk of bleeding. Discuss the risks and benefits of long-term anticoagulation with the person and take their preferences into account.

Indications for screening:

Venous thrombosis

• Patients with unprovoked (or provoked by minor risk factor) VTE test for antiphospholipid syndrome alone, unless meets further criteria below
• Patients with unprovoked VTE at an unusual site, especially intra-abdominal thrombosis - testing to exclude a myeloproliferative disorder, PNH or anti phospholipid syndrome
• Patients with an unprovoked (or provoked by minor risk factor) VTE where a first degree relative has also had VTE. This is the only patient group where NICE (NG158) suggest performing inherited thromobophilia testing, however opinions and guidelines vary.
• Also consider testing patients who develop unprovoked venous thromboembolism at <40 years old, especially if family history of VTE.

Patients who have recurrent unprovoked VTE will likely need long term anticoagulation regardless of the result. In this case testing will not influence management and anticoagulation should not be stopped so that testing can be performed.

Family screening (NOT recommended by NICE NG158)

• First degree family members of patients with a known high-risk thrombophilia (esp. AT, PC, PS), where knowledge of a thrombophilic defect may be useful (e.g. daughters of child-bearing age).

Family screening for low-risk inherited thrombophilia is not routinely recommended.

Family screening in the context of a family history of VTE, but without a known inherited thrombophilia, is not routinely recommended. It is important to recognise that thrombophilia testing is not comprehensive and only includes the most common and serious abnormalities. A negative screen does not exclude a familial predisposition to thrombosis unless there is a known identifiable thrombophilia in the symptomatic relatives.

Obstetrics / Neonates

• Testing before commencing COC/HRT is not recommended, as even if a first degree family member is known to have a thrombosis, a negative result does not exclude an increased risk of venous thrombosis. This is especially true where it is not known if a thrombophilia is present in the index case.
• Test for anti-phospholipid syndrome if history of previous unprovoked VTE or adverse pregnancy outcomes (e.g. recurrent or late pregnancy loss). Testing during pregnancy itself can be unreliable.
• Test for antithrombin deficiency if known family history of AT deficiency or evidence of heparin resistance.
• Test for protein S and protein C deficiency if neonatal / childhood purpura fulminans

Testing

Cannot be performed at the time of an acute thrombotic event or while a patient is on anticoagulation. The majority of patients will require samples to be taken 46 weeks after the completion of anticoagulation.

Referral:

• Consider haematology referral if patient meets criteria for testing as mentioned above. We would prefer to perform the counselling and testing ourselves rather than see patients following testing performed in the community (samples also need to arrive at the laboratory as soon as possible)

References:

Arachchillage D, Mackillop L, et al. Thrombophilia testing: a British Society for Haematology Guideline. Br J Haematol 2022. DOI: 10.1111/bjh.18239

NICE. NG158 Venous Thromboembolic diseases: diagnosis, management and thrombophilia testing. March 2020, update August 2023

• South Tees Hospitals