Protein C
Protein C is a vitamin K dependent plasma protein that inhibits coagulation. For Protein C to serve as an anticoagulant, it must be converted to its active form by thrombin. After activation it potently inhibits coagulation by inactivating Factors V and VIII, and enhances fibrinolysis by neutralizing an inhibitor of plasminogen activator.
Most affected individuals are teenagers or young adults who are heterozygous for the deficiency. Homozygous individuals usually do not survive the neonatal period.
The clinical syndromes associated with hereditary deficiency of Protein C include:
- recurrent venous thromboembolism
- warfarin skin necrosis
- purpura fulminans in neonates.
Indications for Protein C assay include the investigation of any patient with unexplained thromboembolism, especially venous, particularly if thrombotic episodes:
- occur at a relatively young age
- are recurrent,
- are associated with a positive family history of thrombotic disease.
Over 60 families have been described with Protein C deficiency. Affected heterozygous family members have Protein C levels between 40 and 65% of normal, associated with an increased incidence of thromboembolic disease (predominantly venous). It appears, however, that most subjects with heterozygous Protein C deficiency are asymptomatic. Perhaps an additional as yet unidentified risk factor exists in those subjects who develop thrombosis.
Skin necrosis may develop in patients with reduced Protein C levels at the beginning of warfarin therapy. This is due to a transient hypercoagulable state following the rapid warfarin-induced fall in Protein C levels, before the levels of Factors II, IX, and X decrease.
Neonates with homozygous Protein C deficiency (Protein C levels close to zero) present with an often fatal syndrome of purpura fulminans with spreading skin necrosis, thrombosis and disseminated intravascular coagulation (DIC).
Acquired Protein C deficiency may be seen in a wide variety of clinical situations including DIC, extensive thrombosis, liver disease, after surgery, and malignancy. It is uncertain whether or not acquired deficiency contributes to a thrombotic tendency. Since acquired deficiencies of Protein C occur frequently in hospitalized patients, it is preferable to perform the assays at a time when the patient is in stable condition, and ideally in remission from thrombotic events.
Since Protein C is a vitamin K dependent protein, decreased levels may be expected if a patient is on oral anticoagulant drug therapy. Testing for protein C should be deferred until a patient has been off oral anticoagulants for at least 10 days. If it is not possible to discontinue oral anticoagulants and protein C assay is felt to be essential, consideration should be given to stopping the warfarin for 10 days prior to the assays while the patient is temporarily covered with heparin (standard or low molecular weight).
Reference range is 70 – 140% for the functional assay and 65 – 140% for the antigenic assay. A Protein C level of less than 55% is usually indicative of hereditary deficiency in a stable non-anticoagulated adult. A level of 55-65% may indicate either a low normal value or mild hereditary deficiency. In general, a diagnosis of hereditary deficiency of Protein C should only be made when a low value has been obtained after repeated testing (after a 4-6 week interval), and the possibility of acquired deficiency has been excluded. Testing of family members may be helpful in confirming the diagnosis.
Specimen requirement is one light blue top (sodium citrate) tube of blood.
