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Protein C/protein S

Category Haematology >> Specialised Coagulation Services
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:

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Sample & container required 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.

Adult Reference Range:

Note: The reference ranges for use on patients over the age of 16 years, has been locally verified in accordance with CLSI Guideline EP28-A3c through evaluation on representative normal individuals across the sites to reflect our patient population.

Data sourced via Stago from:
Monagle P. et al. Thromb Haemost 2006; 95: 362-372.
Summerhayes R. et al. J Thromb Haemost, 2007; 5, Supp 2: P-M-105.
Summerhayes R. et al. J Thromb Haemost, 2007; 5, Supp 2: P-S-397.

Paediatric Reference Range

Note: Due to the complexity of collecting blood samples for analysis on normal neonates and paediatric patients, the reference ranges for use on patients up to 16 years of age have been taken from published data, from a research study using comparable methodology and equipment as that currently employed in our organisation. Please contact the laboratory for coagulation paediatric ranges.

Data sourced via Stago from:
Monagle P. et al. Thromb Haemost 2006; 95: 362-372.
Summerhayes R. et al. J Thromb Haemost, 2007; 5, Supp 2: P-M-105.
Summerhayes R. et al. J Thromb Haemost, 2007; 5, Supp 2: P-S-397.