Download PDF
Semin Thromb Hemost 2008; 34(4): 335-339
DOI: 10.1055/s-0028-1085475
© Thieme Medical Publishers

Antiprothrombin Antibody Testing: Detection and Clinical Utility

Kenji Oku1 , Tatsuya Atsumi1 , Olga Amengual1 , Takao Koike1
  • 1Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Further Information

Publication History

Publication Date:
23 September 2008 (online)

    Permissions and Reprints

ABSTRACT

Anticardiolipin antibody (aCL), anti-β2 glycoprotein I antibodies, and lupus anticoagulant (LA) are the only laboratory tests considered within the revised criteria for the classification of the antiphospholipid syndrome (APS). Recently, antibodies against phosphatidylserine-prothrombin complex (aPS/PT) have been detected, and these antibodies, rather than antibodies against prothrombin alone, are closely associated with APS and LA. The sensitivity and specificity of aPS/PT for the diagnosis of APS were assessed in a population of patients with a variety of autoimmune disorders. aCL and aPS/PT have similar diagnostic value for APS, therefore aPS/PT should be further explored, not only for research purposes but also as a candidate for one of the laboratory criteria for the classification of the APS.

KEYWORDS

Antiprothrombin antibody - phosphatidylserine - thrombosis - lupus anticoagulant - antiphospholipid syndrome

REFERENCES

  • 1 Hughes G R. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant.  Br Med J (Clin Res Ed). 1983;  287 1088-1089
    CrossrefPubMedGoogle Scholar
  • 2 Khamashta M A. Hughes Syndrome: Antiphospholipid Syndrome. 2nd ed. London, UK; Springer-Verlag 2006: 3-8
    Google Scholar
  • 3 Galli M, Comfurius P, Maassen C et al.. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor.  Lancet. 1990;  335 1544-1547
    CrossrefPubMedGoogle Scholar
  • 4 Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease.  Lancet. 1990;  336 177-178
    PubMedGoogle Scholar
  • 5 McNeil H P, Simpson R J, Chesterman C N, Krilis S A. Anti-phospholipid antibodies are directed against a complex antigen that induces a lipid-binding inhibitor of coagulation: β2-glycoprotein I (apolipoprotein H).  Proc Natl Acad Sci U S A. 1990;  87 4120-4124
    CrossrefPubMedGoogle Scholar
  • 6 Bevers E M, Galli M, Barbui T, Comfurius P, Zwaal R F. Lupus anticoagulant IgG's (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin.  Thromb Haemost. 1991;  66 629-632
    PubMedGoogle Scholar
  • 7 Chow B K, Ting V, Tufaro F, MacGillivray R T. Characterization of a novel liver-specific enhancer in the human prothrombin gene.  J Biol Chem. 1991;  266 18927-18933
    PubMedGoogle Scholar
  • 8 Mann K G, Nesheim M E, Church W R, Haley P, Krishnaswamy S. Surface-dependent reactions of the vitamin K-dependent enzyme complex.  Blood. 1990;  76 1-16
    PubMedGoogle Scholar
  • 9 Loeliger A. Prothrombin as a co-factor of the circulating anticoagulant in systemic lupus erythematosus?.  Thromb Diath Haemorrh. 1959;  3 237-256
    PubMedGoogle Scholar
  • 10 Bajaj S P, Rapaport S I, Fierer D S, Herbst K D, Schwartz D B. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome.  Blood. 1983;  61 684-692
    PubMedGoogle Scholar
  • 11 Edson J R, Vogt J M, Hasegawa D K. Abnormal prothrombin crossed-immunoelectrophoresis in patients with lupus inhibitors.  Blood. 1984;  64 807-816
    PubMedGoogle Scholar
  • 12 Fleck R A, Rapaport S I, Rao L VM. Anti-prothrombin antibodies and the lupus anticoagulant.  Blood. 1988;  72 512-519
    PubMedGoogle Scholar
  • 13 Oosting J D, Derksen R HWM, Bobbink I WG, Hackeng T M, Bouma B N, de Groot P G. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism?.  Blood. 1993;  81 2618-2625
    CrossrefPubMedGoogle Scholar
  • 14 Wu J R, Lentz B R. Phospholipid-specific conformational changes in human prothrombin upon binding to procoagulant acidic lipid membranes.  Thromb Haemost. 1994;  71 596-604
    PubMedGoogle Scholar
  • 15 Zwaal R F, Comfurius P, Bevers E M. Lipid-protein interactions in blood coagulation.  Biochim Biophys Acta. 1998;  1376 433-453
    CrossrefPubMedGoogle Scholar
  • 16 McDonald J F, Shah A M, Schwalbe R A, Kisiel W, Dahlback B, Nelsestuen G L. Comparison of naturally occurring vitamin K-dependent proteins: correlation of amino acid sequences and membrane binding properties suggests a membrane contact site.  Biochemistry. 1997;  36 5120-5127
    CrossrefPubMedGoogle Scholar
  • 17 Galli M, Beretta G, Daldossi M, Bevers E M, Barbui T. Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies.  Thromb Haemost. 1997;  77 486-491
    PubMedGoogle Scholar
  • 18 Bevers E M, Zwaal R F, Willems G M. The effect of phospholipids on the formation of immune complexes between autoantibodies and beta2-glycoprotein I or prothrombin.  Clin Immunol. 2004;  112 150-160
    CrossrefPubMedGoogle Scholar
  • 19 Rao L VM, Hoang A, Rapaport S. Mechanism and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid.  Blood. 1996;  88 4173-4182
    PubMedGoogle Scholar
  • 20 Akimoto T, Akama T, Kono I, Sumida T. Relationship between clinical features and binding domains of anti-prothrombin autoantibodies in patients with systemic lupus erythematosus and antiphospholipid syndrome.  Lupus. 1999;  8 761-766
    CrossrefPubMedGoogle Scholar
  • 21 Arvieux J, Darnige L, Caron C, Reber G, Bensa J C, Colomb M G. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulant.  Thromb Haemost. 1995;  74 1120-1125
    PubMedGoogle Scholar
  • 22 Pengo V, Biasiolo A, Brocco T, Tonetto S, Ruffatti A. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies.  Thromb Haemost. 1996;  75 721-724
    PubMedGoogle Scholar
  • 23 Atsumi T, Ieko M, Bertolaccini M L et al.. Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant.  Arthritis Rheum. 2000;  43 1982-1993
    CrossrefPubMedGoogle Scholar
  • 24 Rauch J, Tannenbaum M, Neville C, Fortin P R. Inhibition of lupus anticoagulant activity by hexagonal phase phosphatidylethanolamine in the presence of prothrombin.  Thromb Haemost. 1998;  80 936-941
    PubMedGoogle Scholar
  • 25 Horbach D A, van Oort E, Derksen R H, de Groot P G. The contribution of anti-prothrombin-antibodies to lupus anticoagulant activity–discrimination between functional and non-functional anti-prothrombin-antibodies.  Thromb Haemost. 1998;  79 790-795
    PubMedGoogle Scholar
  • 26 Amengual O, Atsumi T, Koike T. Specificities, properties, and clinical significance of antiprothrombin antibodies.  Arthritis Rheum. 2003;  48 886-895
    CrossrefPubMedGoogle Scholar
  • 27 Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome.  Blood. 2003;  102 2717-2723
    CrossrefPubMedGoogle Scholar
  • 28 Atsumi T, Amengual O, Yasuda S, Koike T. Antiprothrombin antibodies—are they worth assaying?.  Thromb Res. 2004;  114 533-538
    CrossrefPubMedGoogle Scholar

Dr. Tatsuya Atsumi

Department of Medicine II, Hokkaido University Graduate School of Medicine

N15 W7, Kita-ku, Sapporo 060-8638, Japan

Email: at3tat@med.hokudai.ac.jp

      >