Protein S Antigen

Hormone/ Element

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No Fasting Required

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Anticoagulant protein assay.

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Protein S Antigen Test Information Guide

Why is it done?
- Measures the level of Protein S, a natural anticoagulant produced by the liver that works with Protein C to prevent blood clots
- Evaluates bleeding and clotting disorders, particularly to identify deficiency states that increase thrombosis risk
- Investigates unexplained venous thromboembolism (DVT or PE) or arterial thrombosis, especially in young patients or recurrent cases
- Screens for inherited thrombophilia, particularly when family history of clotting disorders is present
- Monitors anticoagulation therapy effectiveness in patients on warfarin or other anticoagulants
- Assesses risk before surgery, pregnancy, or hormone therapy in patients with known or suspected deficiency
- Performed when patient has symptoms suggestive of thrombophilia or following a documented thrombotic event
Normal Range
- Reference Values: 60-130% of normal activity (or 0.60-1.30 IU/mL) Approximately 24 μg/mL or higher in antigen assays Values vary by laboratory; consult specific reference range provided with test results
- Interpretation Guidelines: Normal Result: Level within laboratory reference range indicates adequate Protein S activity and reduced thrombotic risk
- Low Result (<60%): Indicates Protein S deficiency; may be inherited (Type I, II, or III) or acquired
- High Result (>130%): Unusual; typically not clinically significant; may indicate acute inflammation or other conditions
- Units: Reported as percentage (%) of normal activity or as absolute concentration (IU/mL or μg/mL)
- Critical Values: Generally <20% requires clinical attention and possible intervention
Interpretation
- Low Protein S Levels (<60%): Type I Deficiency: Reduced synthesis of Protein S; both antigen and activity levels are low Type II Deficiency: Dysfunctional Protein S; antigen present but activity reduced Type III Deficiency: Reduced free Protein S; total antigen normal but free fraction decreased Indicates substantially increased risk of thromboembolism, approximately 3-10 times higher than general population
- Acquired Protein S Deficiency: Associated with vitamin K deficiency, liver disease, DIC, nephrotic syndrome, or warfarin therapy May be temporary or permanent depending on underlying cause Often accompanies other coagulation abnormalities
- Normal Protein S Levels (60-130%): Suggests adequate anticoagulant reserve and normal coagulation regulation Reduces likelihood of hereditary thrombophilia related to Protein S deficiency Does not exclude other thrombophilic conditions or acquired thrombotic disorders
- Factors Affecting Results: Anticoagulation therapy (warfarin, heparin) decreases Protein S levels Acute thrombosis or inflammation elevates acute phase reactants and may affect levels Pregnancy and oral contraceptives reduce free Protein S concentration Liver disease impairs synthesis and reduces circulating levels Nephrotic syndrome causes urinary loss of Protein S Timing of testing relative to thrombotic event affects interpretation
- Clinical Significance: Key marker for identifying hereditary thrombophilia Important for risk stratification in patients with unexplained thrombosis Guides decisions regarding anticoagulation prophylaxis May influence management of pregnancy and oral contraceptive use Results should be correlated with clinical presentation and other thrombophilia tests
Associated Organs
- Primary Organ Systems: Liver: Primary site of Protein S synthesis; hepatic dysfunction reduces production Vascular System: Protein S function is critical for preventing thromboembolism in blood vessels Hematologic System: Works with Protein C in coagulation regulation and anticoagulation cascade
- Associated Medical Conditions: Deep Vein Thrombosis (DVT): Abnormal clotting in leg veins Pulmonary Embolism (PE): Blood clot in lung vessels Cerebral Venous Thrombosis: Stroke-like events from clots in brain vessels Mesenteric Venous Thrombosis: Thrombosis affecting intestinal blood supply Arterial Thrombosis: Increased risk of stroke and myocardial infarction Neonatal Purpura Fulminans: Severe thrombotic complication in neonates with severe Protein S deficiency
- Diseases Commonly Associated with Abnormal Results: Hereditary Protein S Deficiency: Autosomal dominant inheritance pattern Liver Cirrhosis: Chronic hepatic disease impairs synthesis Acute Hepatitis: Transient reduction in synthesis Vitamin K Deficiency: Required for Protein S carboxylation and activation Disseminated Intravascular Coagulation (DIC): Consumption of coagulation factors Thrombophilic Disorders: Often combined with Factor V Leiden or Prothrombin mutation
- Potential Complications of Abnormal Results: Recurrent thromboembolism if not adequately managed Failure of anticoagulation therapy if deficiency not recognized Complications during pregnancy including miscarriage and preeclampsia Warfarin-induced skin necrosis in patients with severe deficiency Thrombotic events during surgery or immobilization if not prophylaxed appropriately Increased bleeding risk paradoxically during treatment initiation in severe deficiency
Follow-up Tests
- Complementary Thrombophilia Screening Tests: Protein C Activity: Often decreased concurrently; essential to evaluate anticoagulant reserve Factor V Leiden Mutation: Common hereditary thrombophilia; frequently coexists Prothrombin Gene Mutation (G20210A): Important for complete thrombophilia evaluation Antithrombin III: Another natural anticoagulant; deficiency increases thrombotic risk Lupus Anticoagulant: Associated with acquired thrombophilia Anticardiolipin Antibodies: Markers of antiphospholipid syndrome
- Basic Coagulation Studies: Prothrombin Time (PT/INR): Assesses vitamin K-dependent factors Activated Partial Thromboplastin Time (aPTT): Evaluates intrinsic and common pathway Thrombin Time: Detects abnormalities in fibrinogen conversion Platelet Count: Rules out thrombocytopenia contributing to bleeding or clotting issues Fibrinogen Level: Important in comprehensive coagulation assessment
- Specialized Tests When Indicated: D-dimer: Elevated in acute thrombosis; helps confirm clotting episodes Thrombin-Antithrombin Complex (TAT): Marker of thrombin generation Prothrombin Fragment 1+2: Indicator of prothrombin activation Genetic Testing: DNA sequencing for PROS1 gene mutations in suspected hereditary deficiency
- Imaging and Clinical Follow-up: Doppler Ultrasound: Detect DVT in symptomatic patients CT Pulmonary Angiography: Diagnose pulmonary embolism Compression Ultrasound: Surveillance for occult thrombosis
- Repeat Testing Recommendations: Repeat testing after 8-12 weeks if initial result is borderline or obtained during acute illness Retest after discontinuation of warfarin (wait 2+ weeks) for accurate baseline assessment Annual monitoring in patients with confirmed deficiency to assess trend Preoperative assessment if deficiency confirmed and surgery planned Regular monitoring during pregnancy for patients with known deficiency
- Family Screening: First-degree relatives should be screened if hereditary deficiency confirmed Particularly important for family members planning pregnancy or considering hormonal therapy May guide preventive strategies and risk assessment in relatives
Fasting Required?
- Fasting Status: NO - Fasting is not required for Protein S Antigen testing
- Patient Preparation Instructions: Patient may eat and drink normally before the test No special dietary restrictions required Maintain normal fluid intake; hydration does not affect results
- Medications to Avoid: Do NOT discontinue anticoagulant medications (warfarin, heparin, DOACs) without physician guidance Notify provider if taking anticoagulants; levels will be interpreted accordingly If possible, defer testing until patient is off warfarin for at least 2 weeks for baseline assessment Report all medications to laboratory personnel during specimen collection Estrogen-containing medications (oral contraceptives, HRT) reduce free Protein S; inform provider
- Special Instructions: Wear loose, comfortable clothing to facilitate venipuncture Avoid heavy exertion or strenuous exercise immediately before testing if possible Sit comfortably for 5-10 minutes before blood draw to stabilize vital signs Inform phlebotomist of any recent illness, infection, or inflammation Timing of test may be important; discuss with provider if recent thrombotic event or acute illness Pregnancy status should be disclosed as it affects Protein S levels Inform provider of recent surgery, trauma, or immobilization
- Specimen Collection: Blood drawn via venipuncture into citrate tube (typically 3.2% sodium citrate) Precise tube ratio critical for accurate coagulation studies; follow laboratory protocol Usually single collection sufficient; some labs may recommend repeat in specific circumstances Specimen should be transported promptly to laboratory at room temperature Processing typically occurs within 1-4 hours of collection

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