National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Protein C deficiency

Not a rare disease Not a rare disease
Other Names:
Autosomal recessive thrombophilia due to congenital protein C deficiency; Autosomal recessive thrombophilia due to PC deficiency; Severe hereditary thrombophilia due to congenital protein C deficiency
Categories:
Subtypes:
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.[1][2] 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.[3] [2] 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.[1][3]
Last updated: 6/7/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 10 |
Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormality of the eye
Abnormal eye
0000478
Abnormality of the nervous system
Neurologic abnormalities
Neurological abnormality
[ more ] 		0000707
Autosomal dominant inheritance 0000006
Cerebral venous thrombosis
Blood clot in cerebral vein
0005305
Deep venous thrombosis
Blood clot in a deep vein
0002625
Hypercoagulability 0100724
Pulmonary embolism
Blood clot in artery of lung
0002204
Reduced protein C activity 0005543
Superficial thrombophlebitis 0002638
Warfarin-induced skin necrosis 0001038
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Last updated: 7/1/2020
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.[4] 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.[3]
Last updated: 8/6/2015
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.[4][11633] 

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.[11633] These few cases are inherited in an autosomal recessive way. 
Last updated: 8/6/2015
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.[5]

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.[5]
Last updated: 9/20/2011

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.
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.[6] 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.[3]

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.[7]
Last updated: 9/20/2011

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Protein C deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Protein C deficiency. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • LabTests Online provides information on testing protein C levels in general. Click on LabTests Online to view the information page.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Protein C deficiency. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I have protein C deficiency. My physician recently recommended I start using Pradaxa. Might Pradaxa be useful for anticoagulation therapy with protein C deficiency? See answer

  • I have had protein C deficiency for 20+ years. I have been taking warfarin after initial coumadin treatment. I have had DVT and PE clots but they have not been present since my INR stabilized years ago. What are the long term effects of being on warfarin? I have been told about long term effects of being on other medications but they tell me there are no long term effects of warfarin. Is that correct? See answer

  • Is protein C deficiency inherited from your mother or father? See answer


  1. Congenital protein C or S deficiency. MedlinePlus. February 8, 2012; http://www.nlm.nih.gov/medlineplus/ency/article/000559.htm.
  2. Bauer KA. Protein C deficiency. UpToDate. May 11, 2016; http://www.uptodate.com/contents/protein-c-deficiency.
  3. Cuker A, Pollak ES. Protein C Deficiency. Medscape Reference. January 21, 2016; http://emedicine.medscape.com/article/205470-overview#showall.
  4. Protein C deficiency. Genetics Home Reference. May, 2013; http://ghr.nlm.nih.gov/condition/protein-c-deficiency.
  5. Protein C and Protein S. Lab Tests Online. March 2011; http://labtestsonline.org/understanding/analytes/protein-c-and-s/tab/test. Accessed 9/20/2011.
  6. Congenital protein C or S deficiency. MedlinePlus. March 2010; http://www.nlm.nih.gov/medlineplus/ency/article/000559.htm. Accessed 9/20/2011.
  7. Protein C Deficiency. Clot Connect. June 2011; http://clotconnect.wordpress.com/2011/06/15/protein-c-deficiency/. Accessed 9/20/2011.