Synonym

• PC Antigen
• Protein C antigen
• Protein C functional

Tubes

• Blue top (sodium citrate) tube
• 5 mL venous blood

Additional information

• Avoid warfarin therapy for 2 weeks and heparin therapy for 2 days prior to this test
• Do not draw from an arm with a heparin lock or heparinized catheter
• Avoid venous stasis due to placement of tourniquet for longer than 1 minute
• Draw the blood sample avoiding excessive probing
• Completely fill collection tube and invert it several times to mix sample, gently
• Cap the specimen and place on ice slurry
• Send sample to lab immediately

Info

• Protein C is one of the body’s natural anticoagulant proteins
• Synthesized in the liver in an inactive form
• Circulates in plasma
• Vitamin K dependent
• Protein C test is a qualitative and quantitative estimation of Protein C proenzyme in the blood.
• Thrombin bound to thrombomodulin receptors activates inactive Protein C. The activated Protein C (APC) along with cofactor Protein S, inactivates factors Va and VIIIa, thus preventing extension of intravascular thrombi
• Apart from antithrombotic activity, it exhibits profibrinolytic, anti-inflammatory, and anti-ischemic roles
• Deficiency of Protein C either hereditary or acquired, reduces the anticoagulant effect and can result in a hypercoagulable state

Clinical

• The Protein C assay is indicated in the following conditions:
• To evaluate unexplained venous thrombosis or thromboembolism, especially at younger ages (<50 yrs)
• To aid in the diagnosis of inherited or acquired deficiency of Protein C
• To evaluate clotting disorders in newborns such as disseminated intravascular coagulation or purpura fulminans
• To evaluate women with recurrent midtrimester fetal loss or other adverse pregnancy outcomes
• To evaluate persons at increased risk or having family history of thrombosis
• To determine the cause of thrombosis in unusual sites or massive venous thrombosis
• Deficiency of Protein C may be caused by inherited (congenital) or acquired conditions. Inherited Protein C deficiency is an autosomal dominant disorder. Heterozygous individuals have Protein C levels of 30-60% of normal, while homozygotes have little or no Protein C
• There are two types of congenital Protein C deficiency:
• Type I: Decreased levels of Protein C due to decreased synthesis of a normal protein, detected by functional and antigenic assays
• Type II: Normal levels of Protein C, but decreased functional activity due to production of an abnormally functioning protein, detected only by a functional assay
• Protein C deficiency may clinically present as:
• Most common presentation is deep or superficial venous thrombosis and/or pulmonary embolism
• Apart from thrombosis of deep veins of the lower extremities, it can occur at unusual sites such as:
• Cerebral veins
• Retinal veins
• Mesenteric veins
• Renal veins
• Inferior vena cava
• Hepatic portal veins
• DVT may present as:
• Calf pain
• Edema
• Pain on dorsiflexion of the foot (Homan’s sign)
• Swelling
• Discomfort
• Redness or discoloration at the site
• Cellulitis (uncommon)
• Pulmonary embolism (PE) may present as:
• Dyspnea
• Chest pain
• Syncope
• Cardiac palpitations
• Tachypnea
• Cyanosis
• Arterial thrombotic events are uncommon
• Heterozygous individuals often present with thrombotic episodes before the age of 30 and continue throughout life. They may present as either type I or type II form of deficiency
• Homozygous persons is characterized by rapidly fatal thrombosis in perinatal period, a condition known as purpura fulminans neonatalis
• When treating patients with symptomatic protein C deficiency, heparin or heparinoid therapy is typically indicated while warfarin (Coumadin®) therapy is initiated as warfarin may induce a hypercoagulable state when initiated and result in additional thrombosis and sometimes skin necrosis (characterized by skin and fat necrosis) which can be life threatening
• Thrombosis may be precipitated by:
• Pregnancy
• Surgery
• Trauma
• Use of oral contraceptives
• Neonatal purpura fulminans
• Commonly seen in homozygotes and double heterozygotes for type I and II
• The neonate develops tender ecchymoses (subcutaneous thrombosis) on the head, trunk and extremities. These skin lesions coalesce and then slowly ulcerate leading to necrosis, often accompanied with cerebral infarction and DIC
• It rapidly progresses to gangrene and shock followed by coma and death

Additional information

• Thrombosis as a result of Protein C deficiency occurs in 0.5% of the general population
• Protein C levels decreases with age
• Interpretation of an abnormally low protein C must be correlated with the clinical setting, anticoagulant therapy, DIC, and liver disease. There is overlap between lower limits of normal values and values found in heterozygotes
• Functional assays are recommended for initial evaluation because of their greater sensitivity
• Women with prior thromboembolism or with a strong family history of thromboembolism should be evaluated for thrombophilia before oral contraceptives are administered
• Factors interfering with test results include:
• Recent acute thrombotic event or administration of warfarin or heparin anticoagulant therapy within 2 weeks of test
• Use of oral contraceptives
• Hemolysis due to excessive probing at venipuncture site or rough handling of sample
• Vascular injury during phlebotomy (activates platelets and coagulation factors)
• Venous stasis
• Lipemic or icteric serum
• Incompletely filled tubes, contamination with heparin, or clotted specimens
• Related laboratory tests include
• Anticardiolipin antibody
• Antithrombin III
• Complete blood count
• Fibrin degradation products (FDP)
• Fibrinogen
• Homocysteine
• Lupus anticoagulant
• Protein C resistance test
• Protein S

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

*Qualitative units are in % or U/mL as compared to "normal activity"

**Quantitative is in % or U/mL of normal protein C antigen

-Normals for pediatrics increase progressively with age

High Result

Conditions associated with elevated protein C levels include:

• Diabetes
• Nephrotic syndrome
• Drugs
• Desmopressin
• Heparin
• Oral contraceptives

Low Result

Conditions associated with decreased protein C levels include:

• Acquired
• Acute respiratory distress syndrome (ARDS)
• Disseminated intravascular coagulation (DIC)
• Deep vein thrombosis (DVT)
• Hemolytic-uremic syndrome
• Infection
• Liver disease (13-25%)
• Malignancy
• Pulmonary embolism (PE)
• Post-operative state
• Pregnancy
• Vitamin K deficiency
• Drugs
• Fluorouracil
• L-Asparaginase therapy
• Warfarin
• Congenital
• Homozygous
• Heterozygous

References

• ARUP's Laboratories®. Protein C, Functional. [Homepage on the Internet] ©2007. Last accessed on March 27, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0030113.jsp
• Dhainaut JF et al. Soluble thrombomodulin, plasma-derived unactivated protein C, and recombinant human activated protein C in sepsis. Crit Care Med. 2002 May;30(5 Suppl):S318-24.
• eMedicine from WebMD®. Protein C Deficiency. [Homepage on the Internet] ©1996-2006. Last updated on June 30, 2006. Last accessed on March 27, 2007. Available at URL: http://www.emedicine.com/med/topic1923.htm
• Lab Lines. Warfarin-Induced Skin Necrosis. Last accessed on May 8, 2007. Available at URL: http://pathology.uc.edu/LABLINES/V7I6.pdf
• Laboratory Corporation of America. Protein C Deficiency Profile. [Homepage on the internet]©2007. Last accessed on March 27, 2007. Available at URL: http://www.labcorp.com/datasets/labcorp/html/chapter/mono/cf004100.htm
• LabTestsOnline®. Protein C and Protein S. [Homepage on the Internet]©2001-2007. Last reviewed on July 18, 2005. Last accessed on March 27, 2007. Available at URL: http://www.labtestsonline.org/understanding/analytes/protein_c_and_s/glance.html
• Macias WL et al. New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). Crit Care. 2005;9 Suppl 4:S38-45. Epub 2005 Aug 25
• Molina AMA et al. [Hypercoagulable state due to acquired protein C resistance, harbinger of colonic neoplasm?] [Article in Spanish]. An Med Interna. 2006 Dec;23(12):591-2.
• Sen K et al. Management of neonatal purpura fulminans with severe protein C deficiency. Indian Pediatr. 2006 Jun;43(6):542-5.
• Steinkamp M et al. Chronic disseminated intravascular coagulation and childhood-onset skin necrosis resulting from homozygosity for a protein C Gla domain mutation, Arg15Trp. J Pediatr Hematol Oncol. 2002 Nov;24(8):685-8.
• van Vlijmen EF et al. Oral contraceptives and the absolute risk of venous thromboembolism in women with single or multiple thrombophilic defects: results from a retrospective family cohort study. Arch Intern Med. 2007 Feb 12;167(3):282-9.