Choosing Wisely:

Don’t test for Protein C, protein S, or antithrombin (ATIII) levels during an active clotting event to diagnose a hereditary deficiency because these tests are not analytically accurate during an active clotting event.

Rationale and Comments: These assays may be useful to test for an acquired deficiency (i.e., disseminated intravascular coagulation) in consumptive coagulopathies. These tests are not analytically accurate during an active clotting event. Moreover they are not clinically actionable at the time of an acute clot, because the same therapeutic intervention (anticoagulation) is performed regardless of the results. Deferral to the outpatient/nonacute setting allows for the testing to be done at a time when the results would change patient management (i.e., ceasing or continuing anticoagulation). Because anticoagulation may also impact the determination of results (e.g., protein C and protein S decrease on warfarin, while ATIII is actually elevated), testing while on anticoagulants may also yield misleading results and should be avoided.
Sponsoring Organizations:
  • American Society for Clinical Pathology
  • Sources:
  • Expert consensus
  • Disciplines:
  • Hematologic
  • References: • Marlar, RA. Gusman, JN. Laboratory Testing Issues for Protein C, Protein S, and antithrombin. [Internet]. 2014. [cited 2017 July 31]. Available from
    • McPherson R, Pincus M. 2011. Henry’s clinical diagnosis and management by lab methods (22nd edition). St. Louis, MO: Elsevier.
    • Shen, Y., Tsai, J., Taiwo, E., Gavva, C., et al. Analysis of thrombophilia test ordering practices at an academic center. 2016. [cited 2017 July 31]. Available from

    Email Alerts

    Don't miss a single issue. Sign up for the free AFP email table of contents.

    Sign Up Now