Download PDF
Thromb Haemost 1984; 51(03): 371-375
DOI: 10.1055/s-0038-1661104
Original Article
Schattauer GmbH Stuttgart

Acquired Factor XI Inhibitors in Two Patients with Hereditary Factor XI Deficiency

Kangathevy Morgan
The Departments of Medicine and Biochemistry, University of Southern California, School of Medicine, Los Angeles, California, U.S.A.
,
Sandra Schiffman
The Departments of Medicine and Biochemistry, University of Southern California, School of Medicine, Los Angeles, California, U.S.A.
,
Donald Feinstein
The Departments of Medicine and Biochemistry, University of Southern California, School of Medicine, Los Angeles, California, U.S.A.
› Author Affiliations
Further Information

Publication History

Received 28 December 1983

Accepted 06 April 1984

Publication Date:
19 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Two patients with hereditary factor XI deficiency developed inhibitors following plasma transfusions. Neither had severe spontaneous bleeding. The patients’ plasmas neutralized both factor XI in plasma, purified factor XI, and purified factor XIa. The inhibitor in both patients’ plasmas adsorbed to Protein A- Sepharose. The inhibitors eluted from Protein A-Sepharose were partially neutralized by kappa and lambda light chain antisera indicating that they were polyclonal IgG antibodies. Both inhibitors markedly decreased adsorption of factor XI to glass surfaces. The cleavage of factor XI by trypsin was unaffected by the inhibitors. The lack of severe spontaneous bleeding in both of these patients strongly suggests that an alternate coagulation mechanism bypassing factor XI must compensate for this severe defect.

Keywords

Factor XI inhibitors - Factor XI deficiency
 

  • References

  • 1 Feinstein DI. Acquired inhibitors against factor VIII and other clotting proteins. In: Colman RW, Hirsh J, Marder VG, Saltzman EW. (eds) Textbook of Hemostasis and Thrombosis. p 563 Lippincott; Philadelphia and Toronto: 1982
    Google Scholar
  • 2 Castro O, Farber LR, Clyne LP. Circulating anticoagulant against factors IX and XI in SLE. Ann Intern Med 1972; 77: 543-548
    CrossrefPubMedGoogle Scholar
  • 3 Aberg H, Nilsson IM. Recurrent thrombosis in a young man with a circulating anticoagulant directed against factors XI and XII. Acta Med Scand 1972; 192: 419-425
    PubMedGoogle Scholar
  • 4 Cronberg S, Nilsson IM. Circulating anticoagulants against factor XI and XII together with massive spontaneous platelet aggregation. Scand J Haematol 1973; 10: 309-314
    PubMedGoogle Scholar
  • 5 Krieger H, Leddy JP, Breckenridge RT. Studies on a circulating anticoagulant in systemic lupus erythematosus; Evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XI a). Blood 1975; 46: 189-197
    PubMedGoogle Scholar
  • 6 Fischer DS, Clyne LP. Circulating factor XI antibody and disseminated intravascular coagulation. Arch Intern Med 1981; 141: 515-517
    CrossrefPubMedGoogle Scholar
  • 7 Poon MC, Saito H, Koopman WJ. Characterization of a unique and potent factor XI (PTA) inhibitor. Blood 1981; 58 Supplement (Suppl. 01) 224 a (Abstract)
    PubMedGoogle Scholar
  • 8 Josephson AM, Lisker R. Demonstration of a circulating anticoagulant in PTA deficiency. J Clin Invest 1958; 37: 148-152
    CrossrefPubMedGoogle Scholar
  • 9 Stem DM, Nossel HL, Owen J. An acquired antibody to factor XI in a patient with congenital factor XI deficiency. J Clin Invest 1982; 69: 1270-1276
    CrossrefPubMedGoogle Scholar
  • 10 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurements with the folin phenol reagent. J Biol Chem 1951; 193: 265-275
    PubMedGoogle Scholar
  • 11 Proctor RR, Rapaport SI. Partial thromboplastin time with kaolin: A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol 1961; 36: 212-219
    CrossrefPubMedGoogle Scholar
  • 12 Rapaport SI, Ames SB. Clotting factor assays for plasma from patients receiving intramuscular or subcutaneous heparin. Am J Med Sci 1957; 234: 678-686
    CrossrefPubMedGoogle Scholar
  • 13 Lee SL, Sanders M. A disorder of blood coagulation in systemic lupus erythematosus. J Clin Invest 1955; 34: 1814-1822
    CrossrefPubMedGoogle Scholar
  • 14 Mannhalter C, Schiffman S, Jacobs A. Trypsin activation of human factor XI. J Biol Chem 1979; 255: 2667-2669
    PubMedGoogle Scholar
  • 15 Schiffman S, Lee P. Partial purification and characterization of contact activation cofactor. J Clin Invest 1975; 56: 1082-1092
    CrossrefPubMedGoogle Scholar
  • 16 Thorell JI, Johansson BG. Enzymic iodination of polypeptides with 125I to high specific activity. Biochim Biophys Acta 1971; 251: 363-369
    CrossrefPubMedGoogle Scholar
  • 17 Laemmli UK. Cleavage of structural proteins during assembly of the head of bacteriophage T. Nature 1970; 227: 680-685
    CrossrefPubMedGoogle Scholar
  • 18 Ratnoff OD. The biology and pathology of the initial stages of blood coagulation. Prog Hematol 1966; 5: 204-245
    PubMedGoogle Scholar
  • 19 Revak SD, Cochrane CG, Bouma BN, Griffin JH. Surface and fluid phase activities of two forms of activated Hageman factor produced during contact activation of plasma. J Exp Med 1978; 147: 719-729
    CrossrefPubMedGoogle Scholar
  • 20 Osterud B, Rapaport SI. Activation of factor IX by the reaction product of tissue factor and factor VII: Additional pathway for initiating blood coagulation. Proc Natl Acad Sci, USA 1977; 74: 5260-5264
    CrossrefPubMedGoogle Scholar
  • 21 Zur M, Nemerson Y. Kinetics of factor IX activation via the extrinsic pathway. J Biol Chem 1980; 255: 5703-5707
    PubMedGoogle Scholar