Protein C deficiency: causes, blood clot risk, testing and management

Blood is designed to clot when we are injured, and also to stop clotting when it is no longer needed. Protein C is one of the natural proteins that keeps the clotting process in check. MedlinePlus Genetics explains that protein C blocks the activity of certain proteins that promote clotting. People with protein C deficiency do not have enough working protein C to do this, so the blood has a greater tendency to form abnormal clots.

The deficiency is caused by changes (mutations) in a gene called PROC. MedlinePlus Genetics describes two types: type I, where less protein C is made, and type II, where an altered protein C with reduced activity is made. Both can be associated with a mild or severe form of the condition, depending on how many altered gene copies a person has.

Protein C deficiency belongs to a wider group called inherited thrombophilias. Patient.info lists factor V Leiden, prothrombin 20210G>A, and deficiencies of antithrombin, protein C and protein S as the main inherited causes that increase the risk of a first venous thromboembolism (VTE). It adds that a person's risk is the product of genetic, acquired and circumstantial factors together, rather than the gene change alone.

Patient.info estimates that moderate protein C deficiency affects about 1 in 500 people, and MedlinePlus Genetics gives a similar figure for the mild form. Most of those people never know they have it. The severe form is far rarer, at around 1 in 4 million newborns according to both sources.

Because inheritance is autosomal dominant, a parent with one altered gene copy has a chance of passing it to each child. The NHS thrombophilia page notes that if you have inherited thrombophilia there is a chance you could pass the condition on to any children you have, and that your doctor can tell you more.

The NHS says most people do not realise they have thrombophilia until it causes a blood clot. Having the deficiency does not cause symptoms by itself. The signs are the signs of a clot or, in the severe form, of the clotting problem in newborn babies.

• Throbbing or cramping pain, swelling and warm or discoloured skin in one leg, which the NHS lists as possible signs of a deep vein thrombosis (DVT).

• Sudden difficulty breathing, chest pain or coughing up blood, which can be signs of a clot in the lungs (pulmonary embolism).

• Repeated miscarriages, which the NHS names as a possible sign of thrombophilia.

• In newborns with severe deficiency, purpura fulminans, described by MedlinePlus Genetics as widespread small clots with large purple patches on the skin.

The NHS advises asking for an urgent GP appointment or getting 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, difficulty breathing or are coughing up blood. These could be signs of a clot in a leg or lung.

It says to call 999 or go to A&E if you have severe difficulty breathing, pain in your chest or upper back, a very fast heartbeat, or someone has passed out. The NHS also advises not to drive yourself to A&E.

The NHS says you may be offered a blood test for thrombophilia if you have had a blood clot that is not obviously explained, if a close family member (parent, brother or sister) has inherited thrombophilia, or if you have had 3 or more miscarriages. Blood tests can check for altered genes or changes in blood cells linked to thrombophilia, and scans may be used to look at blood vessels.

Patient.info's professional article makes clear that testing is not routine. It states that testing after a venous clot is not recommended as a routine to guide management, and that routine testing of first-degree relatives is not recommended. It does say that selective testing of relatives of people with protein C, protein S or antithrombin deficiency may be considered where it could influence management and life choices. It also advises that testing should not be carried out during an acute clot or during the initial three-month period of anticoagulation.

Neonates and children with purpura fulminans are the exception. The same article says they should be tested urgently for protein C and protein S deficiency.

There is currently no cure for thrombophilia caused by inherited gene changes, according to the NHS. If your doctor thinks your overall risk of a clot is low, you may not need any treatment. If you do, you will usually be offered an anticoagulant medicine, which makes the blood less likely to clot.

Patient.info's professional article describes how decisions are made in general terms. Short-term preventive treatment is considered at times of raised risk for people with known thrombophilia or a previous clot. After a first clot, long-term anticoagulation is generally not indicated for everyone, because the risks outweigh the benefits, while people with two or more spontaneous clots may be considered for indefinite treatment. It also notes that oestrogen-containing contraception and HRT increase clot risk and should generally be avoided in thrombophilia, whereas progestogen-only contraceptives can be used. These are general principles, and a haematologist applies them to the individual.

Severe protein C deficiency in a newborn is a medical emergency that is managed by specialist paediatric and haematology teams, and the sources used here do not set out a standard treatment for it in lay terms. Parents of an affected baby will be guided by that team.

The NHS says that for many people thrombophilia does not have a big impact on life. It suggests staying active, losing weight if overweight, drinking plenty of water, wearing flight socks on long flights, not smoking, limiting alcohol and not sitting still for long periods where possible.

It also advises telling your doctor or healthcare professional that you have thrombophilia before any medical procedure or before starting any new prescription medicine, including contraception, because some medicines may not be safe and extra treatment or monitoring may be needed. The NHS DVT page adds that if a hospital team thinks you are at higher risk of DVT they may give preventive medicine or compression stockings.

Pregnancy needs planning. The NHS says that if you have thrombophilia and are pregnant or planning a pregnancy you should contact your GP, because you may need additional treatment and monitoring to reduce complications. The NHS DVT page notes that pregnancy and the 6 weeks after having a baby are times of higher DVT risk in general.

In the NHS, protein C deficiency is usually investigated and followed up by a haematology team after a GP referral, often after a clot or because of a family history. Blood testing, anticoagulant treatment and pregnancy planning advice are provided through NHS haematology and, where relevant, obstetric services.

Some people choose private haematology consultations or private blood tests, usually to speed up access or obtain a second opinion. The tests and the treatment principles are the same, and the timing of testing matters more than the sector. Ask which team will interpret the results and which will take responsibility for treatment plans around surgery and pregnancy.