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Thromb Haemost 2002; 88(06): 919-923
DOI: 10.1055/s-0037-1613334
Review Article
Schattauer GmbH

Intracranial Hemorrhage in Systemic Lupus Erythematosus Associated with an Autoantibody against Factor XIII

Laszlo Lorand
1   Department of Cell and Molecular Biology and the Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, IL, USA
,
Pauline T. Velasco
1   Department of Cell and Molecular Biology and the Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, IL, USA
,
John M. Hill
2   Department of Hematology and Medical Oncology, National Naval Medical Center, Bethesda MD, USA
,
Karen J. Hoffmeister
2   Department of Hematology and Medical Oncology, National Naval Medical Center, Bethesda MD, USA
,
Fredric J. Kaye
3   Center for Cancer Research, NCI, NIH, National Naval Medical Center, Bethesda, MD, USA
› Author Affiliations
Further Information

Publication History

Received 11 January 2002

Accepted after resubmission 08 July 2002

Publication Date:
09 December 2017 (online)

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Summary

Intracranial hemorrhage in a young woman with systemic lupus erythematosus necessitated two surgical evacuations. In the absence of a family history of bleeding, clot solubility in urea suggested a factor XIII (FXIII) inhibitor. The patient’s IgG bound well to the virgin and the thrombin-modified zymogen ensemble (A2B2 and A2’B2) and to the free rA2 but reacted poorly with the thrombin-modified rA2’. Since the IgG did not block the thrombin-catalyzed proteolysis of A subunits nor the dissociation of the A2’B2, its action might be to interfere with the release of activation peptides from the thrombincleaved zymogen, hindering the conformational change necessary for generating FXIIIa.

Treatment with cryoprecipitate and cyclophosphamide arrested the hemorrhage and almost neutralized the antibody so that the patient’s clot became insoluble in urea and showed a close to normally cross-linked γ-γ and αn fibrin chain profile. Nevertheless, she still has detectable anti-FXIII antibody and may be at risk for hemorrhage.

Keywords

Lupus - factor XIII autoantibody
 

  • References

  • 1 Lorand L, Losowsky MS, Miloszewski KJM. Human Factor XIII: Fibrin stabilizing factor. In: Progress in Hemostasis and Thrombosis. Spaet TH. Vol. 5. New York: Grune & Stratton; 1980: 245-90.
    Google Scholar
  • 2 Lorand L. Acquired inhibitors of fibrin stabilization: A class of hemorrhagic disorders of diverse origins. In: Anticoagulants, Physiologic, Pathologic and Pharmacologic. Green D. Boca Raton: CRC Press; 1994: 169-91.
    Google Scholar
  • 3 Lorand L. A study on the solubility of fibrin clots in urea. Hung Acta Physiol 1948; 01: 192-6.
    PubMedGoogle Scholar
  • 4 Laki K, Lorand L. On the solubility of fibrin clots [abstract]. Science 1948; 108: 280.
    CrossrefPubMedGoogle Scholar
  • 5 Rosenberg RD, Colman RW, Lorand L. A new haemorrhagic disorder with defective fibrin stabilization and cryofibrinogenaemia. Br J Haematol 1974; 26: 269-84.
    CrossrefPubMedGoogle Scholar
  • 6 Lorand L, Credo RB, Janus TJ. Factor XIII (fibrin stabilizing factor). Methods Enzymol 1981; 80: 333-41.
    PubMedGoogle Scholar
  • 7 Bishop PD, Teller DC, Smith RA, Lasser GW, Gilbert T, Seale RL. Expression, purification , and characterization of human factor XIII in Saccharomyces cerevisiae . Biochemistry 1990; 29: 1861-9.
    CrossrefPubMedGoogle Scholar
  • 8 Lorand L, Velasco PT, Rinne JR, Amare M, Miller LK, Zucker ML. Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system. Proc Natl Acad Sci USA 1988; 85: 232-6.
    CrossrefPubMedGoogle Scholar
  • 9 Credo RB, Curtis CG, Lorand L. α-Chain domain of fibrinogen controls generation of fibrinoligase (coagulation factor XIIIa). Calcium ion regulatory aspects. Biochemistry 1981; 20: 3770-8.
    CrossrefPubMedGoogle Scholar
  • 10 Lorand L, Campbell-Wilkes LK, Cooperstein L. A filter paper assay for transamidating enzymes using radioactive amine substrates. Anal Biochem 1972; 50: 623-31.
    CrossrefPubMedGoogle Scholar
  • 11 Schwartz ML, Pizzo SV, Hill RL, McKee PA. Human Factor XIII from plasma and platelets. Molecular weights, subunit structures, proteolytic activation, and cross-linking of fibrinogen and fibrin. J Biol Chem 1973; 248: 1395-407.
    PubMedGoogle Scholar
  • 12 Lorand L. Factor XIII: structure, activation, and interactions with fibrinogen and fibrin. Ann N Y Acad Sci 2001; 936: 291-311.
    CrossrefPubMedGoogle Scholar
  • 13 McGehee WG, Feinstein DI, Carpenter G, Rapaport SI. Factor XIII inhibitor in a patient receiving INH [abstract]. Clin Res 1971; 19: 180.
    PubMedGoogle Scholar
  • 14 Seiving B, Henriksson P, Stenberg P, Nilsson IM. A reversed activity staining procedure for detection of an acquired antibody against factor XIII in a girl with factor XIII deficiency. Br J Haematol 1992; 82: 414-6.
    CrossrefPubMedGoogle Scholar
  • 15 Manco-Johnson M, Nuss R, Lefkowitz J, Nugent D. Characterization and quantitation of an inhibitor to the A chain of Factor XIII (F XIII) in a child with severe factor XIII deficiency [abstract]. Blood 1993; 82: 596a.
    PubMedGoogle Scholar
  • 16 Ahmad F, Solymoss S, Poon M-C, Berube C, Sullivan AK. Characterization of an acquired IgG inhibitor of coagulation factor XIII in a patient with systemic lupus erythematosus. Br J Haematol 1996; 93: 700-3.
    CrossrefPubMedGoogle Scholar
  • 17 Hill JM, Johnson K, Hoffmeister K, Kaye F, Frame JN, Alving BM, Velasco PT, Lorand L. Management of intracerebral hemorrhage secondary to an acquired inhibitor of factor XIII [abstract]. Blood 1996; 88: 75b.
    PubMedGoogle Scholar
  • 18 Nakazawa M, Iida R, Tanoue K, Arai M. Successful gastrectomy in a patient with inhibitor activities to factor XIII and phospholipid-mediated clotting time [abstract]. Thromb Haemost 1997; 35: PS-137.
    PubMedGoogle Scholar
  • 19 Huth-Kühne A, Lages P, Zimmermann R. Intracranial hemorrhage in a patient with congenital factor XIII deficiency and inhibitor – successful treatment with Ig-immunoadsorption and high dose continuous factor XIII infusion [abstract]. Blood 1998; 92: 106b.
    PubMedGoogle Scholar
  • 20 Schilling FH, Mikkola H, Metzner HJ, Reiter W, Treuner J. Polyclonal immune response to exogenous F XIII in a patient with congenital F XIII-A deficiency carrying a novel mutation of the F XIII-A gene [abstract]. Blood 1999; 94: 92b.
    PubMedGoogle Scholar
  • 21 Fardella P, Conte G, Gonzalez N, Cuneo M. An acquired inhibitor to factor XIII (case report) [abstract]. Blood 1999; 94: 95b.
    PubMedGoogle Scholar
  • 22 Standen G, Birchall J, Morse C, Chamberlain-Webber R. A large bruise. Lancet 1999; 353: 1934.
    CrossrefPubMedGoogle Scholar
  • 23 Milner GR, Holt PJL, Bottomley J, MacIver JE. Practolol therapy associated with a systemic lupus erythematosus-like syndrome and an inhibitor of factor XIII. J Clin Pathol 1977; 30: 770-3.
    CrossrefPubMedGoogle Scholar
  • 24 Ayoub O, Aljurf M, Al Nounou R, Chaudbri NA. Systemic lupus erythematosus presenting with haemorrhagic manifestation. Clin Lab Haematol 1999; 21: 413-6.
    CrossrefPubMedGoogle Scholar
  • 25 Jones DW, MacKie IJ, Gallimore MJ, Winter M. Antibodies to factor XII and recurrent fetal loss in patients with the anti-phospholipid syndrome. Br J Haematol 2001; 113: 550-2.
    CrossrefPubMedGoogle Scholar
  • 26 Erkan D, Bateman H, Lockshin MD. Lupus anticoagulant-hypoprothrombinemia syndrome associated with systemis lupus erythematosus: report of 2 cases and review of literature. Lupus 1999; 08: 560-4.
    CrossrefPubMedGoogle Scholar
  • 27 Yacobovich JR, Uziel Y, Friedman Z, Radnay J, Wolach B. Diffuse muscular haemorrhage as presenting sign of juvenile systemic lupus erythematosus and lupus anticoagulant hypoprothrombinaemia syndrome. Rheumatology 2001; 40: 585-7.
    CrossrefPubMedGoogle Scholar
  • 28 Donohoe S, MacKie IJ, Isenberg D, Machin SJ. Anti-prothrombin antibodies: assay conditions and clinical associations in the anti-phospholipid syndrome. Br J Haematol 2001; 113: 544-9.
    CrossrefPubMedGoogle Scholar
  • 29 Nojima J, Kuratsune H, Suehisa E, Futsukaichi Y, Yamanishi H, Machii T, Iwatani Y, Kanakura Y. Association between the prevalence of antibodies to β2-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications. Clin Chem 2001; 47: 1008-15.
    PubMedGoogle Scholar
  • 30 Schulman S, Langevitz P, Livneh A, Mortinowitz U, Seligsohn U, Varon D. Cyclosporine therapy for acquired factor VIII inhibitor in a patient with systemic lupus erythematosus. Thromb Haemost 1996; 76: 344-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Lafferty TE, Smith JB, Schuster SJ, DeHoratius RJ. Treatment of acquired factor VIII inhibitor using intravenous immunoglobulin in two patients with systemic lupus erythematosus. Arthritis Rheum 1997; 40: 775-8.
    CrossrefPubMedGoogle Scholar
  • 32 Trotta F, Bajocchi G, La RCorte, Moratelli S, Sun LY. Long-lasting remission and successful treatment of acquired factor VIII inhibitors using cyclophosphamide in a patient with systemic lupus erythematosus. Rhematology 1999; 38: 1007-9.
    PubMedGoogle Scholar
  • 33 Ishikawa T, Tsukamoto N, Suto M, Uchiumi H, Mitsuhashi H, Yokohama A, Maesawa A, Nojima Y, Naruse T. Acquired hemophilia A in a patient with systemic lupus erythematosus. Intern Med 2001; 40: 541-3.
    CrossrefPubMedGoogle Scholar
  • 34 Soff GA, Green D. Autoantibody to von Willebrand factor in systemic lupus erythematosus. J Lab Clin Med 1993; 121: 424-30.
    PubMedGoogle Scholar
  • 35 Viallard JF, Pellegrin JL, Vergnes C, Borel-Derlon A, Clofent-Sanchez G, Nurden AT, Leng B, Nurden P. Three cases of acquired von Willebrand disease associated with systemic lupus erythematosus. Br J Haematol 1999; 105: 532-7.
    CrossrefPubMedGoogle Scholar
  • 36 Michiels JJ, Schroyens W, van der Planken M, Berneman Z. Acquired von Willebrand syndrome in systemic lupus erythematodes. Clin Appl Thromb Hemost 2001; 07: 106-12.
    CrossrefPubMedGoogle Scholar