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Activated Protein C Resistance (Factor V Leiden) Assay 

  • Author: Christopher P Kellner, MD; Chief Editor: Thomas M Wheeler, MD  more...
Updated: Aug 01, 2014

Reference Range

The normal reference value for the activated protein C resistance (APCR) ratio is greater than 2.1.



See the list below:

  • Heterozygous carriers of factor V Leiden typically have APCR ratios in the range of 1.5 -1.8.
  • Homozygotes for factor V Leiden usually have APRC ratios of less than 1.5.

Collection and Panels

Specifics for collection and panels are as follows:

  • Specimen type: Platelet-poor plasma
  • Container: Vacutainer, light blue top (citrate; see the image below)
    Light blue top (citrate). Light blue top (citrate).
  • Collection method: Venipuncture
  • Specimen volume: 3 mL

Other instructions are as follows:

  • Spin down, remove plasma, and spin plasma again
  • Freeze 1-mL aliquots of the specimen at 40°C or less within 4 hours


Venous thrombosis panel

Related tests include the following:

  • Antithrombin
  • Protein C
  • Protein S
  • Homocysteine
  • Methylenetetrahydrofolate reductase (MTHFR)
  • Factor V Leiden mutation PCR assay



Activated protein C (APC) is the enzymatically active form of protein C after proteolytic cleavage by thrombomodulin-bound thrombin. An important natural anticoagulant, APC inactivates factors Va and VIIa. APC resistance (APCR) is a hypercoagulability disorder in which factor V cannot be inactivated by APC. In the vast majority of cases, the patient with APCR carries the Leiden variant of factor V, in which the APC cleavage site on factor V is altered. The factor V Leiden mutation is not uncommon, with the heterozygous carrier state occurring in up to 5% of the US population. Factor V Leiden is found in 30-50% of patients with recurrent venous thromboembolism (VTE) and is the most common hereditary cause of thrombosis.[1, 2, 3, 4]

APCR is characterized by a reduced anticoagulant response after a standard amount of APC is added to a plasma specimen. The APCR assay uses snake venoms to activate factor V and prothrombin, thus triggering the lower portion of the clotting pathway and eliminating interference by factor VIII and by lupus anticoagulants (in the absence of phospholipid complexes). Although the APCR assay is no longer based directly on the activated partial thromboplastin time (aPTT), it is expressed as a ratio of aPTT with APC:aPTT without APC. The assay is highly sensitive and specific for factor V Leiden, with excellent discrimination between normal individuals and factor V Leiden heterozygous carriers. The assay is not affected by anticoagulation with standard or low molecular weight heparin or with warfarin.


Indications for APCR ratio testing include the following:

  • Incident or recurrent VTE
  • Family history of VTE
  • Recurrent miscarriage or complications of pregnancy
  • History of arterial thrombosis in a younger patient (< 50 yrs)
  • History of arterial thrombosis in a patients with no other risk factors for atherosclerosis
  • Patients with abnormal APCR ratios should have genetic testing to confirm factor V Leiden mutation status.
Contributor Information and Disclosures

Christopher P Kellner, MD Resident Physician, Cerebrovascular Research Laboratory, Department of Neurological Surgery, Columbia University Medical Center, New York Presbyterian Hospital

Christopher P Kellner, MD is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, Congress of Neurological Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Thomas M Wheeler, MD Chairman, Department of Pathology and Immunology, WL Moody, Jr, Professor of Pathology, Professor of Urology, Baylor College of Medicine

Thomas M Wheeler, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Medical Association, American Society for Clinical Pathology, American Society of Cytopathology, American Thyroid Association, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Harris County Medical Society

Disclosure: Received stock from PathXL for medical advisory board. for: PathXL, Inc.


Judy Lin, MD

Disclosure: Nothing to disclose.

  1. Burris CA, Ashwood ER, Burns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis: Elsevier Saunders; 2006. 1633:962-967.

  2. McPherson RA, Matthew R. Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia: Elsevier Saunders; 2011. 254-5.

  3. Karmacharya P, Aryal MR, Donato A. Mesenteric vein thrombosis in a patient heterozygous for factor V Leiden and G20210A prothrombin genotypes. World J Gastroenterol. 2013 Nov 21. 19(43):7813-5. [Medline]. [Full Text].

  4. Ghatak T, Singh RK, Baronia AK. Spontaneous central vein thrombosis in a patient with activated protein C resistance and dengue infection: An association or causation?. J Anaesthesiol Clin Pharmacol. 2013 Oct. 29(4):547-9. [Medline]. [Full Text].

Light blue top (citrate).
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