Protein C Deficiency

What is protein C deficiency?

Protein C deficiency is a rare disorder that causes abnormal clotting of your blood.

Protein C is one of many natural anticoagulants in blood that helps keep your clotting mechanism in check. An anticoagulant is a substance that prevents blood from clotting. Protein C deficiency means you don’t have enough of this substance (protein C) to protect you from excessive clotting. Your blood naturally needs to clot to stop internal bleeding. However, an excessive amount of clotting can lead to life-threatening problems including deep vein thrombosis and pulmonary embolism.

How common is protein C deficiency?

A mild form of protein C deficiency affects about one in every 200 to 500 people in the general population. A more severe form affects about one in every 500,000 to 750,000 people in the general population, although this is probably an underestimation. Males and females are equally affected.

What are the signs and symptoms of protein C deficiency?

If you have the mild form of protein C deficiency, you’re at risk for:

• Blood clots in your veins (also called venous thromboembolism). Blood clots usually form in your legs (deep vein thrombosis) but can also form in the veins of the large and small intestines, your brain, the main vein to your liver and in other areas. You may not have symptoms until adulthood or may not have symptoms at all. Blood clots are more likely to develop with increasing age.

If your baby has the severe form of protein C deficiency, symptoms may develop within hours to days of their birth. Symptoms include:

• Blood clots mainly in blood vessels in the arms and legs, but could appear anywhere. These blood clotting conditions are known as purpura fulminans and disseminated intravascular coagulation.
• Abnormal bleeding into the affected areas.
• Large purple patches or spots on the skin anywhere on the body.

What causes protein C deficiency?

Protein C deficiency can be caused by a mutation in a gene called PROC. The PROC gene provides the instructions for making protein C. People with the mild form of protein C deficiency have either low levels of protein C (Type I) or have a normal level but a protein C that doesn’t function normally (Type II).

A child of a couple in which one parent has a single PROC gene mutation has a 50% chance of inheriting the mutated gene. If that happens the child will be heterozygous, having one mutated PROC gene. The other will be normal and the child will be mildly affected. A child of a couple in which both parents have a mutated PROC gene has a 25% chance of getting both copies of the mutation. That child will have a much lower protein C level and will be severely affected at birth.

Are all forms of protein C deficiency inherited?

Protein C deficiency can also develop under certain conditions:

• Vitamin K deficiency.
• Warfarin therapy.
• Severe liver disease.
• Disseminated intravascular coagulation (DIC).
• Severe bacterial infection (sepsis).

How is protein C deficiency diagnosed?

Your healthcare provider will make the diagnosis based on the following information and laboratory tests:

• Personal history of having blood clots.
• Family history of having blood clots.
• Blood tests that determine the level of protein C activity and the level of protein C itself.
• Genetic testing to detect mutation in PROC gene (but not needed to confirm diagnosis).

How is protein C deficiency treated?

Treatment depends on the form of protein C deficiency and severity of your symptoms.

If you have a mild form of protein C deficiency, you may receive:

• No treatment: Most people don’t need treatment except during surgery or if they are pregnant, have experienced trauma (such as a car accident) or are physically inactive.
• Treatment with an anticoagulant: If you have had a blood-clotting (thrombotic) event.

If warfarin is used, heparin must be started first to prevent a complication in which there is widespread clotting, including in the skin and soft tissues. However, other anticoagulants are now available that don’t have this requirement. Whatever anticoagulant is used, your healthcare provider will monitor your therapy closely. Never stop any medication on your own. If you have a concern, call your provider, or if you have bleeding, seek emergency care.

In infants with the severe form of protein C deficiency who have purpura fulminans and other types of thrombosis, protein C concentrate (Ceprotin®) or fresh frozen plasma may be used.

What are the complications of protein C deficiency?

Complications of protein C deficiency include:

• Widespread thrombosis due to warfarin treatment. First, painful reddish or purple lesions form most commonly on your torso, arms or legs soon after starting warfarin. Without treatment, this can lead to the death of skin and other tissues.
• Blood clots (deep vein thrombus) that can break off and lodge in your lung (pulmonary embolism).
• Purpura fulminans (blood clotting problem throughout an infant’s body). This condition can be fatal without treatment.
• Fluid overload in infants who need to be treated with fresh frozen plasma.

Can protein C deficiency be prevented?

Because protein C deficiency is an inherited disorder, it can’t be prevented. However, parents and children may wish to meet with a hematologist to learn more about protein C deficiency and undergo laboratory testing.

Protein C deficiency can also develop as the result of other conditions, which may or may not be preventable. In women, the risk of clotting is increased by medications that contain estrogen, such as oral contraceptive pills. Smoking, obesity, pregnancy and inactivity further increase the clotting risk in protein C deficiency. In some cases, preventive doses of anticoagulants are given to decrease this risk.

What can I expect if I have been diagnosed with protein C deficiency?

Infants with severe protein C deficiency have a poor prognosis and may die soon after birth. Treatment with frequent infusions of plasma can cause a buildup of fluid, which contributes to the high rate of infant deaths. Not enough information is available about the long-term outcome of people with severe congenital protein C deficiency.

If you have mild protein C deficiency, you’re at increased risk of developing recurrent blood clots in your veins (venous thromboembolism) that can travel and lodge in your lungs (pulmonary embolism). To achieve the best outcome, be sure to keep all your follow-up appointments with your healthcare provider. They can closely monitor your condition and start or change treatments as needed.

Do blood clots develop in arteries in people with protein C deficiency?

Researchers don’t know for sure if blood clots develop in arteries. However, there are reports of an increased risk of stroke in people with protein C deficiency.

Are there risk factors that can trigger blood clots in people with protein C deficiency?

Possible risk factors are being inactive for long periods of time, being pregnant, experiencing a traumatic injury or having had recent surgery.

A note from Cleveland Clinic

Protein C deficiency is a rare condition that can increase your risk of developing blood clots. Many people with protein C deficiency don’t have symptoms and may not need treatment. If you do need treatment, follow your healthcare provider’s instructions and keep all of your follow-up appointments. You and your provider will work closely together to reduce your risk of developing blood clots.