A new method for characterization and epitope determination of a lupus anticoagulant-associated neutralizing antiprothrombin antibody.

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    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 0370470 Publication Model: Print Cited Medium: Print ISSN: 0002-9173 (Print) Linking ISSN: 00029173 NLM ISO Abbreviation: Am J Clin Pathol Subsets: MEDLINE
    • Publication Information:
      Publication: 2016- : Oxford : Oxford University Press
      Original Publication: Philadelphia [etc.] Lippincott [etc.]
    • Subject Terms:
    • Abstract:
      A patient had both lupus anticoagulant hypoprothrombinemia syndrome and celiac disease. The presence of a neutralizing antiprothrombin antibody in the patient's serum was demonstrated by coagulation tests, immunoadsorption, and Western blot analysis. The probable cause for the severe hypoprothrombinemia was clearance of prothrombin-antibody complexes from the circulation. Studies showed the antiprothrombin antibody binding to human prothrombin was phospholipid- and Ca(++)-independent; the antibody did not bind to human thrombin. The target epitope of the antibody was studied by Western blot analysis of mutated recombinant human prothrombin molecules. The antibody reacted with the fragment 2-A region of prothrombin, spanning the second kringle domain and the thrombin A chain within prothrombin. Based on this new method, the proposed mechanism for the neutralizing action of the antibody is impairment of prothrombin activation by the prothrombinase complex, either by steric hindrance of the hydrolysis of prothrombin by factor Xa or by interference of the interaction of prothrombin with factor Va; both reactions are required for efficient conversion of prothrombin to thrombin.
    • Accession Number:
      0 (Epitopes)
      0 (Lupus Coagulation Inhibitor)
      9001-26-7 (Prothrombin)
    • Publication Date:
      Date Created: 19970201 Date Completed: 19970306 Latest Revision: 20190512
    • Publication Date:
      20221213
    • Accession Number:
      10.1093/ajcp/107.2.197
    • Accession Number:
      9024068