Rare Cardiology News

Disease Profile

Protein C deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

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

Blood Diseases; Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

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]

Symptoms

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.

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

Cause

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]

Diagnosis

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]

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    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]

    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.

    Organizations

    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

      Organizations Providing General Support

        Learn more

        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

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • MedlinePlus Genetics contains information on Protein C deficiency. This website is maintained by the National Library of Medicine.
        • 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.

            References

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

            Rare Cardiology News