Imperial Collage Healthcare

Protein C/protein S

Lab Code : PROC/PRSF

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 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.

Reference Range

Protein C
                                         Protein C Antigen
Adult > 6 months               0.70 - 1.40 IU/ml
Paediatric (<6 Months)       0.70 - 1.40 IU/mL

The following reference ranges are for Protein C activity and Free Protein S antigen:

Sample Required
4 x 2.7 mL sodium citrate (pale blue top) adults 4 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 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.

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