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  • Title: Laboratory identification of factor inhibitors: an update.
    Author: Kershaw G, Favaloro EJ.
    Journal: Pathology; 2012 Jun; 44(4):293-302. PubMed ID: 22531341.
    Abstract:
    Coagulation factor inhibitors comprise antibodies that bind to and then neutralise specific pro-coagulant plasma proteins. Coagulation factor inhibitors can develop against any coagulation factor, although the most common are against factor VIII (FVIII). These can develop in individuals with inherited haemophilia A (HA) as an immune response to factor replacement therapy, or as auto-antibodies leading to the condition of acquired HA. Clinical suspicion for inhibitors may arise when individuals present with bleeding symptoms without any prior bleeding diathesis, or when a patient with known mild haemophilia presents with a bleeding diathesis more extreme to their usual presentation, or when there is failure of factor replacement therapy to arrest bleeding in a known haemophiliac. The laboratory identification of factor inhibitors requires a careful and systematic approach that excludes other possible causes of prolonged screening tests, most commonly the activated partial thromboplastin time (APTT), and sometimes prothrombin time (PT). Coagulation factor inhibitor studies, including the Bethesda assay, are then undertaken to measure inhibitor titre, which guides treatment. This paper overviews the laboratory investigation of factor inhibitors, and also briefly reviews recent cross-laboratory inhibitor studies and the most recent evidence related to differential inhibitor formation according to type of therapy.
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