Antithrombin III

Antithrombin (formerly called antithrombin III) is a protein from the liver that slows down clotting. It switches off thrombin and some other clotting factors, so that a clot does not grow larger than needed. Heparin, an anticoagulant, works by strengthening antithrombin. This test measures the activity of antithrombin in percent of normal: how well the antithrombin that is present does its inhibiting work.

• A hereditary shortage of antithrombin: a rare cause of thrombosis at a young age or of thrombosis in the family
• An acquired shortage due to liver disease, protein loss through the kidneys or consumption around a thrombosis, surgery or severe illness
• An explanation when heparin does not work well enough

With a low value, the GP repeats the test at a time without thrombosis, surgery or heparin use, and checks liver function and protein loss in the urine. If the activity stays low without an explanation, referral follows to an internist-hematologist for further testing, such as the amount of antithrombin, and testing of family members if needed. A confirmed hereditary shortage can affect how long anticoagulants are used after a thrombosis and the precautions around surgery and pregnancy.

A single low value is not a diagnosis. According to the Dutch Society for Clinical Chemistry (NVKC), a low value is repeated at a later time; a hereditary shortage is only diagnosed with repeated measurements, a measurement of the amount of antithrombin and preferably testing of family members. The Dutch medical specialists' guideline (FMS) on antithrombotic treatment advises against routine testing for hereditary thrombophilia (a hereditary increased clotting tendency), both after a thrombosis and when choosing the contraceptive pill, because the result usually does not change the treatment.

• During and shortly after a thrombosis, surgery or severe illness, the value is often temporarily low; a measurement in that period says little about a hereditary shortage.
• Heparin lowers antithrombin activity; estrogens, such as in the contraceptive pill, and pregnancy can also lower the value.
• Some DOACs can disturb the activity measurement, depending on the laboratory's method.
• Antithrombin is sensitive to the blood draw and transport: the plasma must be separated within a few hours and frozen.

A hereditary antithrombin shortage is rare: an estimated 1 in 2000 to 5000 people. An acquired shortage, for example with liver disease, protein loss or around a thrombosis or surgery, is more common. Thrombosis itself usually has another cause, such as surgery, long periods of bed rest, pregnancy or the contraceptive pill.

Useful at a doctor's request with a thrombosis at a young age or in an unusual place, with repeated thrombosis without a clear trigger, when heparin does not work well enough, and with a known hereditary antithrombin shortage in the family as part of family testing. According to the FMS guideline, testing for a hereditary clotting tendency is not useful for deciding whether you can use the contraceptive pill; with thrombosis in the family, the choice of contraception is weighed based on the family history. In people without thrombosis and without a known shortage in the family, a single value says little.

• A temporarily low value, for example around a thrombosis or surgery or with heparin use, can wrongly look like a hereditary shortage and lead to needless worry and follow-up testing.
• A normal value does not rule out other forms of hereditary clotting tendency, such as factor V Leiden or a shortage of protein C or S, and can be falsely reassuring.

• NVKC, allesovertesten.nl: Antitrombine
• FMS Richtlijn Antitrombotisch beleid: Vrouwen met een verhoogd risico op VTE (hormonale anticonceptie)
• FMS Richtlijn Antitrombotisch beleid: Continueren antistolling na acute veneuze trombo-embolie
• Thuisarts.nl: Ik denk dat ik een trombosebeen heb