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Module COAG-09 · Version 1.0

Distinguishing Factor Deficiency from Inhibition

After a mixing study flags a possible inhibitor, work through choosing factor assays and inhibitor studies, reading one-stage and chromogenic FVIII results together, and recognizing lupus anticoagulant, heparin, and DOAC interference before an inhibitor titer is trusted.

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Who this module is for

Clinical laboratory scientists and trainees working coagulation bench with prior exposure to screening tests and mixing studies.

Learning objectives

  • Select factor assays based on screening and mixing patterns
  • Recognize parallelism, dilution, lupus anticoagulant, heparin, and DOAC interference
  • Explain Bethesda/Nijmegen inhibitor-titer concepts and time-dependent inhibitors

How completion works

Mark every required section done and answer every knowledge check in those sections correctly. The final save completes the module automatically.

Sources

11 sources

  1. 1. Marlar RA, Strandberg K, Shima M, Adcock DM. Clinical utility and impact of the use of the chromogenic vs one-stage factor activity assays in haemophilia A and B. Eur J Haematol. 2020;104(1):3-14. doi:10.1111/ejh.13339.

    Source note · peer-reviewed literature

  2. 2. Tiede A, Collins P, Knoebl P, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica. 2020;105(7):1791-1801. doi:10.3324/haematol.2019.230771.

    Source note · professional society guidance

  3. 3. Verbruggen B, Novakova I, Wessels H, Boezeman J, van den Berg M, Mauser-Bunschoten E. The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitor: improved specificity and reliability. Thromb Haemost. 1995;73(2):247-251.

    Source note · peer-reviewed literature

  4. 4. Miller CH, Platt SJ, Rice AS, Kelly F, Soucie JM. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor measurement during replacement therapy and facilitate inhibitor surveillance. J Thromb Haemost. 2012;10(6):1055-1061. doi:10.1111/j.1538-7836.2012.04705.x.

    Source note · peer-reviewed literature

  5. 5. Chandler WL, Ferrell C, Lee J, Tun T, Kha H. Comparison of three methods for measuring factor VIII levels in plasma. Am J Clin Pathol. 2003;120(1):34-39. doi:10.1309/WHU4-8F3L-LRPT-D1BM.

    Source note · peer-reviewed literature

  6. 6. Moser KA, Smock KJ. Direct oral anticoagulant interference in hemostasis assays. Hematology Am Soc Hematol Educ Program. 2021;2021(1):129-133. doi:10.1182/hematology.2021000254.

    Source note · peer-reviewed literature

  7. 7. Favaloro EJ, Gilmore G, Arunachalam S, Mohammed S, Baker R. Reducing the effect of DOAC interference in laboratory testing for factor VIII and factor IX: a comparative study using DOAC Stop and andexanet alfa to neutralize rivaroxaban effects. Haemophilia. 2020;26(2):354-362. doi:10.1111/hae.13934.

    Source note · peer-reviewed literature

  8. 8. Merck Manual Professional Edition. Overview of liver disease: coagulation abnormalities. https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/manifestations-of-liver-disease/overview-of-liver-disease

    Source note · professional society guidance

  9. 9. Clinical and Laboratory Standards Institute. H47, One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test, 3rd ed. Published 2023-03-07. https://clsi.org/shop/standards/h47/

    Source note · consensus standard

  10. 10. 42 CFR Section 493.1269, Standard: Hematology, Subpart K, Quality System for Nonwaived Testing. https://www.law.cornell.edu/cfr/text/42/493.1269

    Source note · federal guidance

  11. 11. 42 CFR Section 493.1253, Establishment and verification of performance specifications. https://www.law.cornell.edu/cfr/text/42/493.1253

    Source note · federal guidance