Venous thromboembolism is a recognised complication of treatment for childhood acute lymphoblastic leukaemia, driven substantially by asparaginase and by central venous access, and practice around prophylaxis and screening has varied widely. The French Society for Childhood Cancer's leukaemia committee has harmonised it.
Routine screening for inherited thrombophilia is not recommended. Testing is restricted to children with an unexplained personal history of venous thromboembolism or a first-degree family history of inherited thrombophilia — and when it is done, it should be targeted (protein C, protein S, antithrombin, factor V Leiden, prothrombin G20210A) and performed away from asparaginase exposure, because asparaginase depletes antithrombin and will produce a result that means nothing.
Primary prophylaxis is likewise not routine. It may be considered during induction in higher-risk subgroups — T-cell disease, adolescents over 10, overweight patients — particularly where several risk factors coincide, with prophylactic-dose low-molecular-weight heparin first line. For established thromboembolism, heparin is first line, with transition to a direct oral anticoagulant possible in a stable patient after at least five days. Direct oral anticoagulant use here remains off-label, and the recommendations say so.
- Do not send a thrombophilia screen on a child starting ALL treatment unless there is a personal or first-degree family history.
- If testing is indicated, time it away from asparaginase — antithrombin will be low regardless.
- Consider induction prophylaxis only where risk factors stack: T-cell disease, age over 10, overweight.
- Use low-molecular-weight heparin first line for both prophylaxis and treatment; a direct oral anticoagulant is a second-line option and off-label.
- Tailor treatment duration to the thrombosis site, its radiological course and whether asparaginase is continuing — there is no fixed course.
Why it matters
A thrombophilia screen sent during asparaginase produces an abnormal result that has nothing to do with inherited thrombophilia.
Don't overread it
These are national harmonisation recommendations based on literature review and expert consensus, not on new trial evidence.
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