Venous thromboembolism (clots)

Venous thromboembolism is a blood clot in a vein, usually a deep-vein clot in the leg or one that travels to the lungs. This score adds up common clotting variants, including Factor V Leiden and prothrombin G20210A, into one inherited tendency.

What this clot risk score reads

This is PGS002235, built by Kolin and colleagues from UK Biobank data in 2021 using elastic net regression over genome-wide significant clotting variants. Venous thromboembolism means a clot forming in a vein, usually in a leg (deep vein thrombosis) and dangerous mainly when part of it travels to the lungs (pulmonary embolism).

Two of its variants stand out because they are well known in their own right and this site explains both separately: Factor V Leiden and the prothrombin G20210A variant. Between them they account for a large share of inherited clotting tendency in people of European ancestry.

How well it predicts clots

In 269,164 UK Biobank participants with 2,295 incident clots, the top 1% of this score carried 5.37 times the odds of the rest, and the top fifth carried about 3 times the risk of the remaining four fifths.

That is one of the sharper separations among these scores, which follows from clotting genetics having a few strong common variants rather than only tiny effects. Absolute risk still stays low for most people: venous thromboembolism affects on the order of 1 to 2 people per 1,000 per year in the general population, rising steeply with age.

How to read a high or low score

Clot risk is mostly about circumstances meeting a tendency. Surgery, hospital admission, immobility, long-haul travel, pregnancy and the weeks after birth, oestrogen-containing contraception or hormone therapy, active cancer and severe infection are the situations where an inherited tendency turns into an event.

That makes a high score a piece of context worth mentioning to a doctor before elective surgery, before starting oestrogen-containing contraception, or during pregnancy planning, rather than something to act on day to day. Sudden calf swelling and pain, or unexplained breathlessness and chest pain, are always urgent regardless of score.

What this score does not capture

Deficiencies of antithrombin, protein C and protein S are rare but carry much higher clotting risk than any common variant, and they are diagnosed by blood testing and sequencing, not by a chip. Antiphospholipid syndrome, an acquired autoimmune cause, is likewise invisible here.

The reconstruction from a consumer DNA file is also incomplete: several of the published score's variants cannot be read from one, including the single largest-weighted variant in it.

Ancestry and accuracy

This score was developed and validated entirely in European-ancestry UK Biobank participants, and its two flagship variants are strongly ancestry-patterned. Factor V Leiden and prothrombin G20210A are largely European in distribution and rare or absent in East Asian and African populations, so both the score and its percentile mean much less outside that group.

Variants in this score you can read on their own

This score includes variants that this site also explains individually, where you can see what each genotype means on its own: Factor V Leiden thrombophilia (rs6025) · Prothrombin clotting variant (rs1799963).

How much of this score your file covers

29 of the published score's 36 variants are present in a standard consumer DNA file (81%). The remaining 7 cannot be read from one, so a result computed here approximates the published score rather than reproducing it.

Common questions

Does a high clot score mean I should avoid the contraceptive pill or HRT? That is a conversation for a clinician, not a decision for a score. Oestrogen-containing contraception raises clot risk, and it raises it further in people with an inherited tendency, but the absolute risks, the alternatives and your own history all belong in that discussion.

Is this the same as being tested for Factor V Leiden? Not quite. This score includes Factor V Leiden as one of its variants, but a percentile blends it with many others. This site also reads Factor V Leiden and prothrombin G20210A on their own pages, which is the more direct answer if that is the question you have.

What should I do before surgery or a long flight? Mention any known clotting tendency and any family history of clots to the team looking after you, since preventive measures around surgery and hospital stays are standard and effective. General measures like moving regularly on long journeys apply to everyone.

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