When should the test be performed after a thrombotic event?

Wait at least three months after acute thrombosis, when acute-phase reactants such as factor VIII have normalised, to obtain stable baseline results. Testing during or shortly after an event may produce transient false-positive resistance.

Does pregnancy affect the APCR result?

Yes. Pregnancy physiologically lowers the APCR ratio through elevated factor VIII and other pro-coagulant changes, which can mask or mimic inherited resistance. Confirm any positive result with Factor V Leiden genotyping, which is unaffected by pregnancy.

What does a low APCR ratio mean for thrombotic risk?

A low ratio indicating Factor V Leiden increases venous thromboembolism risk approximately three- to eight-fold in heterozygotes and up to 80-fold in homozygotes. Risk is further modified by other thrombophilias, oral contraceptives, pregnancy, surgery, and immobility.

Should asymptomatic family members be tested?

Selective screening of first-degree relatives may be considered when the result will influence management—for example, in pre-conception counselling or before high-risk oestrogen therapy. Routine population or family screening outside a clinical decision context is not recommended.

Is fasting required for the APCR test?

No. The test does not require fasting, though lipaemic specimens can interfere with optical clotting assays and should be avoided.

How long does the result take?

Results are typically available within 3–5 business days from specimen receipt at Quest. Reflex Factor V Leiden genotyping adds several additional days.

BML-CAR-037cardiovascularUSA

Activated Protein C-Resistance

Q: What is the relationship between APCR and Factor V Leiden?

Factor V Leiden is the most common cause of a positive APCR test, accounting for approximately 90–95 per cent of low ratios in European populations. APCR is the functional screen; genotyping provides definitive confirmation.

Q: Can I be tested while on anticoagulation?

Warfarin, heparin, and direct oral anticoagulants can interfere with clotting-based assays and produce unreliable results. Ideally test when off anticoagulation, or use a second-generation dilute-plasma method less sensitive to these drugs and confirm equivocal results with genotyping.

The Activated Protein C-Resistance test measures the prolongation of plasma clotting time in response to exogenous APC, screening for Factor V Leiden and other causes of impaired anticoagulant regulation. A low ratio indicates resistance, conferring increased venous thromboembolism risk;

Biomarkers

Blood (plasma)

Sample

3–5 business days

Turnaround

Fasting

What is the APCR test?

The Activated Protein C-Resistance test is a functional coagulation assay that detects impaired down-regulation of thrombin generation by endogenous anticoagulant protein C. It was designed to screen for Factor V Leiden, the single most common inherited thrombophilia, which accounts for approximately 90–95 per cent of positive APCR results in European populations and confers a three- to eight-fold increased risk of venous thromboembolism in heterozygotes. Practitioners order APCR as part of a thrombophilia work-up in patients with unprovoked or recurrent venous thromboembolism, thrombosis at a young age, or a strong family history. Unlike genotyping, the functional assay captures both the common genetic variant and acquired causes of resistance—pregnancy, oestrogen therapy, and elevated factor VIII—making it a useful screen but necessitating confirmatory DNA testing when positive. Interpretation requires attention to the clinical and treatment context, because heparin, direct oral anticoagulants, and the acute-phase response can all alter clotting-based assays.

What does the APCR test measure?

APCR(Activated Protein C-Resistance Ratio)

Range: ≥2.0 (method-dependent); ratio <2.0 suggests resistance.Optimal: Ratio ≥2.0; values below 2.0 warrant reflex genotyping or repeat testing in a stable clinical state.Ratio

Activated protein C is an endogenous anticoagulant serine protease that, together with its cofactor protein S, inactivates factors Va and VIIIa, thereby down-regulating thrombin generation. The APCR test measures the prolongation of clotting time when exogenous APC is added to patient plasma; in normal plasma the clotting time is substantially prolonged, yielding a high ratio. The most common cause of resistance is the Factor V Leiden mutation (G1691A), which renders factor Va resistant to APC-mediated cleavage; acquired causes include pregnancy, oral contraceptive use, and high factor VIII.

APCR is the functional screening test for Factor V Leiden, the most prevalent inherited thrombophilia in populations of European ancestry. A low ratio indicates that the plasma does not respond normally to APC, conferring increased thrombin generation and venous thromboembolism risk. Because the test is sensitive to physiological variables and acute thrombosis, it is ideally performed when the patient is off anticoagulation and remote from an acute event; a positive functional result is typically confirmed by Factor V Leiden genotyping.

Why is the APCR test ordered?

Investigation of unprovoked or recurrent deep vein thrombosis or pulmonary embolism in adults under 50 years
Thrombophilia screening in patients with a strong family history of venous thromboembolism, particularly in first-degree relatives affected at a young age
Work-up of venous thrombosis at unusual sites—cerebral, mesenteric, or portal vein—when a hypercoagulable state is suspected
Pre-conception or antenatal counselling in women with a personal or family history of pregnancy-associated thrombosis or recurrent pregnancy loss
Assessment of thrombotic risk before long-term oestrogen therapy or oral contraceptive initiation in selected high-risk patients
Evaluation of unexplained or recurrent thrombosis in younger patients where inherited thrombophilia is part of the differential
Selective screening in asymptomatic relatives of probands with confirmed Factor V Leiden when the result will influence management decisions

Sample collection and turnaround

Sample type

Blood (plasma)

Fasting required

Collection method

Venipuncture at patient service centre

Turnaround

3–5 business days

Collection notes

Phlebotomy via Quest draw site. Collect into sodium citrate (blue-top) tube; the specimen must be adequately filled to maintain the correct blood-to-anticoagulant ratio. Process and separate plasma promptly; freeze if not analysed the same day.

Specimen requirements

Sodium citrate plasma, minimum 1.0 mL. Freeze at –20 °C or below if transport or analysis is delayed. Reject haemolysed, lipaemic, or clotted specimens and underfilled tubes. Note whether the patient is on anticoagulation or within three months of an acute thrombotic event, as these factors affect interpretation.

What can affect APCR results?

variableAnticoagulation therapy

Warfarin, heparin, and direct oral anticoagulants alter clotting times and can produce false-positive or false-negative results; ideally test when off anticoagulation or use a second-generation dilute-patient-plasma method less sensitive to these drugs.

variableAcute thrombosis and the acute-phase response

Factor VIII and other acute-phase reactants rise during thrombosis and inflammation, transiently lowering the APCR ratio; test at least three months after an acute event for stable baseline results.

reducesPregnancy and oestrogen therapy

Pregnancy and combined hormonal contraceptives physiologically lower the APCR ratio through elevated factor VIII and other pro-coagulant changes, potentially masking or mimicking inherited resistance; confirm with genotyping if clinically indicated.

reducesElevated factor VIII

High factor VIII—whether genetic, acquired, or acute-phase—is itself a risk factor for thrombosis and lowers the APCR ratio independently of Factor V Leiden.

variableAssay methodology

First-generation clotting-time assays are more susceptible to lupus anticoagulant and anticoagulant drugs; second-generation methods dilute patient plasma with factor-V-deficient plasma to improve specificity, so reference ranges and cut-offs are method-dependent.

What do APCR results mean?

Elevated

A high APCR ratio (≥2.0, method-dependent) indicates normal sensitivity to activated protein C and effectively excludes Factor V Leiden in the assay conditions tested. No further action is required from a haemostatic standpoint, though other thrombophilias may still be present and should be assessed according to clinical suspicion.

Normal

A normal ratio in a patient off anticoagulation and remote from acute thrombosis makes Factor V Leiden and significant acquired APCR unlikely. Clinical thrombophilia assessment should continue with other tests—protein C, protein S, antithrombin, prothrombin G20210A—as guided by history and pre-test probability.

Reduced

A low ratio (<2.0) indicates resistance to activated protein C. In approximately 90–95 per cent of cases in European populations this reflects heterozygous or homozygous Factor V Leiden; confirm with Factor V Leiden genotyping. Acquired causes—pregnancy, oestrogen therapy, high factor VIII, lupus anticoagulant, acute thrombosis—should be considered and the test repeated in a stable state if transient interference is suspected. A confirmed positive result informs thrombotic-risk stratification, duration of anticoagulation, family counselling, and avoidance of high-dose oestrogen where feasible.

Note: APCR is a screening test, not a diagnostic endpoint; positive results require genotyping for definitive confirmation and genetic counselling. Timing matters—test when off anticoagulation, outside pregnancy, and at least three months post-event. Second-generation dilute-plasma assays are less sensitive to lupus anticoagulant and oral anticoagulants but reference intervals remain method-specific, so interpret with the performing laboratory's cut-off. An isolated APCR result does not dictate management; it is one variable in a multifactorial risk assessment that includes thrombosis characteristics, family history, and other laboratory and clinical findings.

Frequently asked questions

Factor V Leiden is the most common cause of a positive APCR test, accounting for approximately 90–95 per cent of low ratios in European populations. APCR is the functional screen; genotyping provides definitive confirmation.

How to access the APCR test

The APCR reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.

Create Free Account

About this page

Published: October 7, 2026

Last reviewed: October 7, 2026

References:

Kujovich JL. Factor V Leiden thrombophilia. Genet Med. (2011)
Lijfering WM, et al. Risk of venous thrombosis in carriers of a deficiency of antithrombin, protein C, or protein S: a meta-analysis. Thromb Haemost. (2009)
Baglin T, et al. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol. (2010)
Stevens SM, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. (2021)

This content is for licensed healthcare practitioners only and does not constitute medical advice. Clinical decisions should be based on the full clinical picture and not on any single test result.