Imperial Collage Healthcare

Protein C/protein S

Test Background
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 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 fulminars 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.

Reference Range

Protein C 70-140 IU/dL
Protein S free (F) 50-110 IU/dL
Protein S free (M) 70-120 IU/dL

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

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 underfilled, 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.

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