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Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances

Key Points

  • Antiphospholipid syndrome (APS) classification criteria, designed to categorize patient cohorts for clinical research, are commonly used in clinical practice; however, their use might not be appropriate for routine diagnosis

  • Patients with APS can have antiphospholipid antibody (aPL)-related clinical features other than thrombosis and pregnancy morbidity, such as livedo reticularis, thrombocytopenia, nephropathy, valvular heart disease, haemolytic anaemia, chorea and myelitis

  • aPL profiling represents the most accurate risk stratification tool for clinical manifestations such as thrombosis in the context of APS

  • New extra-criteria autoantibodies could improve the accuracy of diagnosis for patients suspected of having APS

Abstract

First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical features of recurrent thrombosis and pregnancy morbidity and persistently test positive for the presence of antiphospholipid antibodies (aPL). At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) criterion have to be met for a patient to be classified as having APS. However, the clinical spectrum of APS encompasses additional manifestations that can affect many organs and cannot be explained exclusively by patients being in a prothrombotic state; clinical manifestations not listed in the classification criteria (known as extra-criteria manifestations) include neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease. Increasingly, research interest has focused on the development of novel assays that might be more specific for APS than the current aPL tests. This Review focuses on the current classification criteria for APS, presenting the role of extra-criteria manifestations and lab-based tests. Diagnostic approaches to difficult cases, including so-called seronegative APS, are also discussed.

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Figure 1: Extra-criteria clinical manifestations of antiphospholipid syndrome.
Figure 2: Mechanisms of thrombogenesis induced by antiphospholipid antibodies.

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S.S. researched data for the article. All authors contributed to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Munther Khamashta.

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Glossary

Livedo reticularis

Cutaneous manifestation characterized by a transient or persistent blotchy, reddish-blue to purple, net-like pattern.

Phlogosis

Inflammation; from Ancient Greek, literally meaning 'burning heat'.

Organizing thrombi with focal recanalization

Thrombi that organize into fibrocellular and fibrous vascular occlusions, which are then recanalized by endothelialized channels following the acute phase of thrombosis, particularly seen in antiphospholipid antibody-related nephropathy.

Thrombotic microangiopathy

A heterogeneous group of pathological features characterised by vascular damage that manifests as arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall.

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Sciascia, S., Amigo, MC., Roccatello, D. et al. Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol 13, 548–560 (2017). https://doi.org/10.1038/nrrheum.2017.124

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