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

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