Protein S deficiency: what it is, symptoms, testing and treatment in the UK

Blood has to clot to stop bleeding, but it also needs to stop clotting once the job is done. Several natural proteins act as brakes on the clotting system. Protein S is one of them. Patient.info describes it as a vitamin K-dependent anticoagulant protein that works as a helper to protein C, another natural anticoagulant, and explains that much of the protein S in the blood is bound to a carrier protein and therefore inactive.

When there is too little working protein S, the brakes are weaker and clots can form more easily. This sits within the wider group of conditions called thrombophilia, which the NHS defines as a condition where the blood clots more easily. Protein S deficiency is one of the less common causes, and it is usually found because someone has had a clot or because a close relative has.

Patient.info describes three types. In type I, the body makes too little structurally normal protein, so both total and free protein S are low. Type II is a problem with how the protein works. In type III, free protein S is low while the total level looks normal. These distinctions matter mainly to the haematology team interpreting the results.

The NHS explains that inherited thrombophilia comes from altered genes you are born with, and that there is a chance of passing an inherited form to any children. Patient.info states that protein S deficiency is inherited in an autosomal dominant pattern, meaning one altered copy of the gene can be enough to lower the level.

A deficiency can also be acquired. Patient.info lists acute thrombosis, vitamin K deficiency, warfarin, nephrotic syndrome, liver disease, antiphospholipid antibodies and disseminated intravascular coagulation among the causes, and notes that protein S levels fall progressively during pregnancy and are lowered to a lesser extent by oestrogen-containing contraceptives or hormone replacement therapy. This is why testing is usually done when someone is well and not at a time that could give a misleading low result.

The same article gives a prevalence of 0.03 to 0.13 per cent in the general population and about 3 per cent among people who have had a venous thromboembolism. It also says the effect of the deficiency is thought to result in part from interaction with other defects, so family history and other risk factors both count.

There are no symptoms of the low protein S level itself. The NHS says most people do not realise they have thrombophilia until it causes a blood clot, and that repeated miscarriages can also be a sign. What people notice is the clot.

• Throbbing or cramping pain in one leg, usually in the calf or thigh.

• Swelling in one leg, sometimes with red, darkened or warm skin.

• Sudden difficulty breathing, chest pain or coughing up blood, which can mean the clot has travelled to the lungs (pulmonary embolism).

• Pain and swelling in an arm or the tummy if that is where the clot is.

The NHS says to ask for an urgent GP appointment or get help from NHS 111 if you have throbbing or cramping pain in one leg, swelling in one leg, red, darkened or warm skin on the leg, sudden difficulty breathing or if you are coughing up blood.

Call 999 or go to A&E if you have severe difficulty breathing, pain in the chest or upper back, a very fast heartbeat or someone has passed out. These can be signs of a pulmonary embolism. The NHS adds that you should not drive yourself to A&E.

For a suspected deep vein thrombosis, NHS guidance on DVT says you should be referred to hospital within 24 hours for an ultrasound scan, and that DVT is treated with blood-thinning medicines such as rivaroxaban for at least 3 months.

The NHS says you may be offered a blood test for thrombophilia if you have had a blood clot with no obvious reason, if a close family member has inherited thrombophilia, or if you have had 3 or more miscarriages. Scans such as ultrasound or CT may be used to look at the blood vessels.

Patient.info explains that a family history is essential in judging how much a deficiency matters for an individual. The laboratory measures protein S antigen, and the free protein S level is the one that should be tested when a deficiency is suspected. Because other things can interfere, over-diagnosis is a recognised risk, and a functional assay is considered if other results are normal and a reliable test can be performed.

Because a clot, pregnancy, warfarin and liver disease can all lower protein S, a single low result is not always the end of the story. A haematologist may repeat the test and look at other thrombophilia tests such as antithrombin, activated protein C resistance, factor V Leiden and antiphospholipid antibodies before concluding that the deficiency is inherited.

The NHS says there is currently no cure for thrombophilia caused by inherited altered genes, whereas acquired thrombophilia can sometimes get better if the underlying cause is treated. If a doctor thinks your overall risk of a blood clot is low, you may not need treatment. If you do, you will usually be offered anticoagulant medicine, which makes the blood less sticky so it is less likely to clot.

Patient.info stresses that bleeding risks must be assessed individually and that no single prescription fits all cases. It advises avoiding drugs that predispose to thrombosis, for example combined oral contraceptives, and refers to separate guidance for acute clots and for pregnancy.

The NHS lists everyday steps: stay active, try to lose weight if you are overweight, drink enough water, wear flight socks on long flights if a pharmacist advises it, and avoid smoking, heavy alcohol use and sitting for long periods without moving.

The NHS says that if you are pregnant or planning a pregnancy and have thrombophilia, you should contact your GP, because you may need additional treatment and monitoring. For anyone with the deficiency, it is worth saying so before surgery, long hospital stays or starting hormone-containing medicines, as the NHS recommends.

Patient.info notes that the outlook depends on early diagnosis, effective measures to prevent thrombosis and good management of any clot that does occur. It also notes that a severe form, with two altered copies of the gene, causes life-threatening problems in newborn babies, which is far rarer and is managed by specialist teams.

For many people the condition has little effect on daily life, as the NHS observes. The practical aim is to know your risk, recognise the signs of a clot quickly and make sure that clinicians looking after you know about it.

On the NHS, testing and follow-up are usually arranged through a GP and a haematology clinic, particularly after an unexplained clot or when a relative has a known deficiency. Treatment of a clot and any long-term anticoagulant plan are provided through the same route.

Some people also see a private haematologist for a faster appointment or a second opinion. Tests and treatments are the same in either setting, and the main differences are waiting time and choice of clinician. Whichever route you use, a clear written summary of your results and your plan is useful to carry to future appointments.