Elsevier

The Lancet

Volume 353, Issue 9161, 17 April 1999, Pages 1348-1353
The Lancet

Series
Antiphospholipid antibodies and thrombosis

https://doi.org/10.1016/S0140-6736(98)10362-8Get rights and content

Summary

Antiphospholipid antibodies are associated with arterial and venous thrombosis, recurrent pregnancy loss, and thrombocytopenia. Although the antibodies have not been conclusively shown to be causal in thrombosis and miscarriage, they are useful laboratory markers for the antiphospholipid syndrome. The identification of the syndrome is clinically important because of the risk of recurrent thrombosis and the need for antithrombotic therapy in many cases. Diagnosis and treatment of antiphospholipid syndrome is difficult, however, because of the protean clinical manifestations and associations, limitations of existing laboratory tests for antiphospholipid antibodies, and the absence of evidence-based guidance on best management.

Section snippets

Antiphospholipid syndrome

Autoantibodies with apparent specificity for negatively charged phospholipids have long been recognised in systemic lupus erythematosus and are associated with thrombotic complications and miscarriage.1, 2 The terms lupus anticoagulant and anticardiolipin are used to describe these antibodies.

The antiphospholipid syndrome may be defined as the occurrence of thrombosis, recurrent miscarriage, or both in association with laboratory evidence of persistent antiphospholipid antibody, 3 either lupus

Antiphospholipid antibodies

Lupus anticoagulant is an immunoglobulin that acts as a coagulation inhibitor, but does not recognise a specific coagulation factor. Lupus anticoagulant slows the rate of thrombin generation, and therefore clot formation in vitro, through interference in the interactions that require phospholipid. It is therefore detected in coagulation assays. The criteria for lupus anticoagulant positivity are an increased clotting time in a phospholipid dependent coagulation test, with evidence of an

Thrombosis in antiphospholipid syndrome

The paradoxical association between a prothrombotic state and the presence of autoantibodies with in-vitro anticoagulant effects is not fully understood. In antiphospholipid syndrome, vascular occlusion is due to thromboembolism, rather than vasculitis. Some arterial events may also be caused by embolisation from sterile vegetations on cardiac valves. Patients with antiphospholipid syndrome have evidence of persistent coagulation activation; there is an increased plasma concentration of markers

Difficulties with diagnosis

Antiphospholipid syndrome is clearly a heterogeneous disorder, both in terms of its clinical manifestations and range of autoantibodies. Because of the perceived high risk of recurrent thrombosis in antiphospholipid syndrome and the efficacy of oral anticoagulant therapy, accurate diagnosis is a clinical imperative.

Diagnosis is dependent on the maintenance of a high index of suspicion and confirmation through laboratory investigation. When arterial or venous thrombosis occur in patients who do

Management of thrombosis and miscarriage

The diagnostic difficulties and range of clinical manifestations in antiphospholipid syndrome make the need for liaison between clinical and laboratory specialists essential in the formulation of strategies for clinical management. There are only limited data from prospective clinical trials on which to base treatment decisions. Therapeutic regimens should be guided by the results of observational studies that support an association between antiphospholipid antibodies and thrombosis,

Future aims

Our understanding of the pathogenesis and clinical features of autoimmune thrombotic disease is increasing rapidly. Antiphospholipid syndrome is a multifaceted and complex condition that is clinically demanding with regard to diagnosis and management. There is a clear need for further studies of the mechanisms involved, for the development of more specific laboratory techniques to identify those patients at increased risk of thrombosis and miscarriage, and for the enrolment of patients in

References (65)

  • EJW Bowie et al.

    Thrombosis and systemic lupus erythematosus despite circulating anticoagulants

    J Lab Clin Med

    (1963)
  • DI Feinstein et al.

    Acquired inhibitors of blood coagulation

    Prog Haemostasis Thrombosis

    (1972)
  • JS Ginsberg et al.

    Antiphospholipid antibodies and venous thromboembolism

    Blood

    (1995)
  • SJ Machin et al.

    Guidelines on testing for the lupus anticoagulant

    J Clin Pathol

    (1991)
  • M Galli et al.

    Anticardiolipin antibodies directed not to cardiolipin but to a plasma protein cofactor

    Lancet

    (1990)
  • HP McNeil et al.

    Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta2-glycoprotein I (apolipoprotein H)

    Proc Nat Acad Sci USA

    (1990)
  • RAS Roubey et al.

    “Anticardiolipin” autoantibodies recognise beta2-glycoprotein I in the absence of phospholipid: importance of antigen density and bivalent binding

    J Immunol

    (1995)
  • SS Pierangeli et al.

    Beta2-glycoprotein I (beta2-GPI) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies

    Br J Immunol

    (1992)
  • J Arvieux et al.

    Measurement of antiphospholipid antibodies by ELISA using beta2-glycoprotein I as an antigen

    J Immunol Methods

    (1991)
  • DM Keeling et al.

    Some `antiphospholipid antibodies' bind to beta 2-glycoprotein I in the absence of phospholipid

    Br J Haematol

    (1992)
  • H Takeya et al.

    Anti-beta 2-glycoprotein I (beta 2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the beta 2GPI binding to phospholipids

    Clin Invest

    (1977)
  • EM Bevers et al.

    Lupus anticoagulant IgGs (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin

    Thromb Haemost

    (1991)
  • ME Martinuzzo et al.

    Anti beta2 glycoprotein I antibodies: detection and association with thrombosis

    Br J Haematol

    (1995)
  • E Matsuura et al.

    Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor

    J Immunol

    (1992)
  • RG Malia et al.

    Inhibition of activated protein C and its cofactor protein S by antiphospholipid antibodies

    Br J Haematol

    (1990)
  • KK Hampton et al.

    Resistance to activated protein C

    N Engl J Med

    (1991)
  • M Galli et al.

    Differential effects of anti-beta 2 glycoprotein I antibodies on the anticoagulant activity of activated protein C

    Blood

    (1998)
  • JD Oosting et al.

    Antiphosphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenetic mechanism?

    Blood

    (1993)
  • S Shibata et al.

    Autoantibodies to heparin from patients with antiphospholipid antibody syndrome inhibit formation of antithrombin III-thrombin complexes

    Blood

    (1994)
  • J Matsuda et al.

    Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody

    Am J Haematol

    (1994)
  • B Godeau et al.

    Specific antiplatelet glycoprotein autoantibodies are associated with the thrombocytopenia of primary antiphospholipid syndrome

    Br J Haematol

    (1997)
  • MB Hill et al.

    Characterisation and specificity of anti-endothelial cell membrane antibodies and their relationship to thrombosis in the primary antiphospholipid syndrome (APS)

    Clin Exp Immunol

    (1995)
  • J Matsuda et al.

    Anti-endothelial cell antibodies to the endothelial hybridoma cell line (Eahy926) in systemic lupus erythematosus patients with antiphospholipid antibodies

    Br J Haematol

    (1997)
  • LFJ Bansci et al.

    Beta2-glycoprotein I deficiency and the risk of thrombosis

    Thromb Haemost

    (1992)
  • SS Pierangeli et al.

    Induction of thrombosis in a mouse model by IgG, IgM and IgA immunoglobulins from patients with the antiphospholipid syndrome

    Thromb Haemost

    (1995)
  • ZM Sthoeger et al.

    Anti-cardiolipin antibodies induce pregnancy failure by impairing embryonic implantation

    Proc Natl Acad Sci USA

    (1993)
  • O Amengual et al.

    The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome

    Thromb Haemos

    (1998)
  • DW Branch et al.

    Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipid syndrome: a possible mechanism of thrombosis

    Am J Obst Gynaecol

    (1993)
  • NJ Lindsey et al.

    Inhibition of prostacyclin release by endothelial binding anticardiolipin antibodies in thrombosis-prone patients with systemic lupus erythematosus and the antiphospholipid syndrome

    Br J Rheumatol

    (1994)
  • NJ Lindsey et al.

    Stimulation of von Willebrand factor antigen release by immunoglobulin from thrombosis prone patients with systemic lupus erythematosus and the antiphospholipid syndrome

    Br j Rheumatol

    (1993)
  • A Bordron et al.

    The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis

    Clin J Inves

    (1998)
  • J Arvieux et al.

    Platelet activating properties of murine monoclonal antibodies to beta2-glycoprotein I

    Thromb Haemost

    (1993)

    • Cited by (0)

    View full text
    Copyright © 1999 Elsevier Ltd. All rights reserved.