Usually ordered as part of a thrombophilia screen. Protein C is a vitamin K-dependent protein that is synthesised in the liver. Hereditary and acquired protein C deficiencies are a known risk factor for venous thrombosis. Heterozygous deficiency of protein C has a prevalence of 1 in 300, the majority of whom are asymptomatic. Homozygous protein C deficiency presents with a form of disseminated intravascular coagulation in newborns (purpura fulminans). Protein C Antigen assay by ELISA is also available to distinguish between type I (quantitative) and type II (qualitative) deficiencies.
Protein S (PS) is a vitamin K-dependent plasma glycoprotein, synthesised in the liver and endothelial cells, that serves as the cofactor for the anticoagulant function of activated protein C (APC) in inactivating factors Va and Vllla. A hereditary or acquired deficiency of PS is associated with a thrombotic tendency. Protein S deficiency accounts for 2-3 % of thrombotic events. The age of onset of thrombosis is generally 10 to 50 years and rarely earlier than 10 years. Type I protein S deficiency (the most common deficiency) is a heterozygous state with a quantitative reduction in protein S levels. Protein S type II deficiencies have normal levels of protein S but a reduced activity – these are very rare. Type III deficiencies are more common than type II and have a normal total protein S level, but a reduced free protein S level.
Clinical Indications • Venous thromboembolism at a young age (including childhood) • Recurrent venous thromboembolism • Unusual site of thrombosis (eg. mesenteric, renal, portal veins, cerebral venous sinuses) • Thrombosis during pregnancy or puerperium • Recurrent superficial thrombophlebitis • Arterial thrombosis at a young age (<40 years) • A family history of any of the above • A first degree relative with diagnosed thrombophilia • Recurrent pregnancy loss (3 or more in the second trimester) • Severe or recurrent intrauterine growth retardation • Severe or recurrent pre-eclampsia • Other recurrent obstetric complications (abruptio placentae, pre-term delivery) • Neonatal purpura fulminans or massive thrombosis in newborn • Warfarin-induced skin necrosis
The link between inherited thrombophilias and adverse pregnancy outcomes is debatable as the evidence for this association is somewhat contradictory.
Protein C Protein C Activity Protein C Antigen Adult > 6 months 0.70 - 1.40 IU/mL 0.70 - 1.40 IU/ml Paediatric (<6 Months) 0.43 - 1.02 IU/mL 0.70 - 1.40 IU/mL
Protein S Free Protein S (Male) Free Protein S (Female) 0.70 - 1.20 IU/mL 0.50-1.10 IU/mL
Sample Required 4 x 4.5 mL sodium citrate (pale blue top) adults4 x 1.8 mL sodium citrate (pale blue top) paediatrics
Turnaround Time 14 days
Notes Special handling: avoid prolonged stasis during venepuncture. Sample must be received by lab within 2 hours of collection. Please note: samples will be rejected if under/over-filled, clotted, haemolysed or if patients are receiving anticoagulant therapy. Similarly, sampling is inappropriate within 4 weeks post-childbirth or during an acute phase inflammatory response.