Protein C deficiency

What causes protein C deficiency?

Protein C deficiency can be inherited or acquired later in life.

Inherited protein C deficiency is caused by mutations in the gene that provides instructions for making protein C, called the PROC gene. These mutations disrupt the protein's ability to control blood clotting. If protein C cannot control blood clotting, abnormal blood clots may form. The mutations are divided into 2 types — type I and type II — on the basis of whether they cause to have lower levels of protein C in the blood (type I) or a functional (type II) deficiency of protein C.

  • Type I deficiency: When people in the family have only one mutated copy of the gene (heterozygous) they typically have levels that are about one half that of normal patient plasma. Some families have a severe form of the disease and some do not have any symptoms even when they have the same mutation.
  • Type II deficiency: Type II protein C deficiency is less common than type I disease, and is associated with decreased function of protein C.

When people have two copies of the altered gene (homozygous) or have two different mutations in each copy of the gene (heterozygous) the disease is very severe and protein C deficiency is classically associated with neonatal purpura fulminans (NPF); intracranial thromboembolism may also occur in babies. Some patients present with venous thromboembolism (VTE) in childhood or adolescence.

Acquired protein C deficiency may be caused by large blood clots, liver disease, disseminated intravascular coagulation (DIC), infection (sepsis), and vitamin K deficiency. Treatment with warfarin or certain types of chemotherapy can also cause acquired protein C deficiency.

Last updated on 05-01-20

How is protein C deficiency diagnosed?

A diagnosis of protein C deficiency might be suspected in someone with a deep venous thrombosis (DVT) or a pulmonary embolism, especially if it occurs in a relatively young person (less than 50 years old) or has formed in an unusual location, such as the veins leading to the liver or kidney or the blood vessels of the brain.

Laboratory tests are usually be done to look at the function or quantity of protein C in the blood. Functional tests are usually ordered, along with other tests for abnormal blood clotting, to screen for normal activity of protein C. Based on those results, concentrations of protein C may be measured to look for decreased production due to an acquired or inherited condition and to classify the type of deficiency. If the shortage of protein C is due to an inherited genetic change, the quantity of protein C available and the degree of activity can be used to help determine whether a person is heterozygous or homozygous for the mutation. Genetic testing is not necessary to make a diagnosis.

Last updated on 05-01-20

How is protein C deficiency inherited?

Protein C deficiency can be hereditary or acquired. Most cases of hereditary protein C deficiency are inherited in an autosomal dominant manner. This means that having only one mutated copy of the responsible gene in each cell (allele) is enough to cause mild protein C deficiency, although some may not have any symptoms. A mutated copy of the gene can be inherited from a person's mother or father.

People who inherit two mutated copies of the gene, one copy from each parent (autosomal recessive protein C deficiency) may have severe protein C deficiency. These few cases are inherited in an autosomal recessive way.

Last updated on 05-01-20

Might Pradaxa be useful for anticoagulation therapy with protein C deficiency?

While we cannot make recommendations for your medical care and recommend you discuss any concerns regarding medication use with your physician, we have found the following resources we hope you find helpful.

The listed uses of Pradaxa (dabigatran) currently include: treatment of thromboembolism (such as deep vein thrombosis or pulmonary embolism), prevention of recurrent thromboembolism in patients who have had a previous event, and prevention of strokes or serious blood clots in people who have atrial fibrillation.

More information on Pradaxa can be found at the following link from MedlinePlus, the National Library of Medicine Web site designed to help you research your health questions. dabigatran-342135#0

While there are limited studies available regarding the use of Pradaxa in individuals who have protein C deficiency, we identified one case report described in the medical literature that you might find helpful. Case reports document clinical findings associated with individual cases. It is important to keep in mind that the clinical findings documented in these case reports are based on specific individuals and may differ from one affected person to another. In this case report, an individual with protein C deficiency was prescribed Pradaxa as an alternative medication to Warfarin to alleviate medication associated side effects. The authors report that the patient had no new episodes of superficial or deep vein thrombosis after six months of therapy.

We additionally located an abstract for a study comparing the use of Pradaxa to Warfarin. The study population included both patients with a history of thrombophilia (either congenital or acquired) and without. A small subset of the studied population had either protein S or protein C deficiency. The researchers found a similar frequency of thrombotic events in patients taking both medications. They did not find a difference in treatment efficacy in the population with thrombophilia.

In reviewing both studies, it is important to note that Coumadin is the brand name for Warfarin.

Last updated on 05-01-20

Are there long-term effects of warfarin?

Coumadin and warfarin are the same medication. Bleeding is the primary adverse effect associated with warfarin. The risk of bleeding may depend on the length of therapy, as well as the intensity of anticoagulation, underlying patient characteristics, and concurrent use of other drugs that impact bleeding or clotting. One study reported that for people on long-term warfarin, there was a 32% increase in all forms of bleeding (minor and major), and a 46% increase in major bleeds for every 10 years of age over 40 years. However, some studies have suggested that bleeding problems are more likely to occur during the first month of taking warfarin rather than later in treatment. The risk of bleeding in people on warfarin is also increased by high blood pressure (hypertension), a history of stroke, kidney problems, cancer, alcoholism, and liver disease.

A number of studies have suggested that the chronic use of warfarin may lead to calcium build-up in the arteries (arterial calcification). However, it has also been suggested that there is no evidence that warfarin increases the risk of complications that are expected in people with increased calcification (such as stroke, myocardial infarction, or peripheral vascular disease).

Other adverse reactions that may occur infrequently with chronic warfarin therapy may include agranulocytosis, hair loss, elevated liver enzyme levels, hepatitis and various other reactions. A more complete list of reactions that may occur with chronic warfarin therapy can be viewed on Medscape's Web site.

You can also visit MedlinePlus to view information about the side effects of warfarin in general.

Last updated on 05-01-20

What is protein C deficiency?

Protein C deficiency is a disorder that increases a person's risk to develop abnormal blood clots due to a deficiency of the Protein C, a protein in the body that prevents blood clotting. It may be inherited or acquired. Inherited deficiency of protein C can lead to familial thrombophilia (increased tendency toward thrombosis). It is caused by mutations in the PROC gene, and in most cases is transmitted in an autosomal dominant way; a few people inherit an abnormal allele from both parents and may have a more severe disease (please see autosomal recessive protein C deficiency) because they have very low levels of active protein C. Acquired protein C deficiency may be caused by large blood clots, liver disease, disseminated intravascular coagulation (DIC), infection (sepsis), vitamin K deficiency, use of warfarin or certain types of chemotherapy. While most people with protein C deficiency do not have problems, some are at risk for a type of clot called deep vein thrombosis (DVT), which can travel through the bloodstream and become stuck in the lung, causing pulmonary embolism. Also, abnormal bleeding can occur in various parts of the body causing purple patches on the skin. Treatment depend on the symptoms severity. Most people do not need any treatment. However, in situations of clot risk such as pregnancy, surgery or trauma, prevention treatment may be indicated.

Last updated on 05-01-20

How might protein C deficiency be treated?

Most people with mild protein C deficiency never develop abnormal blood clots and thus do not require treatment. However, people who have experienced a deep venous thrombosis (DVT) or a pulmonary embolism are usually treated with blood-thinning drugs such as heparin or warfarin, which help to prevent another blood clot from developing in the future. Preventative treatment with these blood-thinning drugs may also be considered in those with a family history of blood clotting, as well as in higher risk situations such as pregnancy.

A protein C concentrate (Ceprotin®) was approved by the Food and Drug Administration in 2007 for the treatment of protein C deficiency. High doses of intravenous protein C concentrates can help thin the blood and protect from blood clots. It can also be used a preventative treatment against blood clots during surgery, pregnancy delivery, prolonged immobility, or overwhelming infection in the blood stream (sepsis). Currently, no guidelines exist as to which patients should receive protein C concentrate. It is typically given only at times of increased risk for clotting, or when the blood thinner heparin by itself cannot be safely given because it would lead to an increased risk for bleeding. However, in those with severe protein C who have had severe bleeding complications on long-term blood thinning therapy, protein C concentrate has been used on a regular basis.

Last updated on 05-01-20

Where To Start

Protein C deficiency - LabTests Online

LabTests Online provides information on testing protein C levels in general. Click on LabTests Online to view the information page.

Last updated on 04-27-20

Clot Connect

Clot Connect, an education and outreach project lead by health care providers at the University of North Carolina at Chapel Hill, has information for patients and healthcare professionals.

Last updated on 04-27-20

Name: National Blood Clot Alliance 8321 Old Courthouse Road Suite 255
Vienna, VA, 22182, United States
Phone: +1-703-935-8845 Toll Free: 1-877-466-2568 (877-4NO-CLOT) Email: Url:
Name: Clot Connect UNC Hemophilia and Thrombosis Center 6340 Quadrangle Drive, Suite 50
Chapel Hill, NC, 27517, United States
Email: Url:

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