Key Issues at the Forefront of Diagnosis and Testing for Antiphospholipid Syndrome

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by antiphospholipid antibodies associated with thrombosis and pregnancy complications. Catastrophic APS is a severe form involving multiple organ systems with a high mortality rate. The pathogenesis involves antiphospholipid antibodies which target phospholipid-binding proteins and damage endothelial cells thus activating coagulation, triggering a pro-thrombotic state. Laboratory tests for antiphospholipid antibody detection include lupus anticoagulant testing in the coagulation laboratory and serological detection of anticardiolipin and anti-beta 2 glycoprotein I antibodies. Despite recent updates in the diagnostic criteria for APS the recent decades and our improved knowledge of this disease, there remain several key issues pertaining to diagnosis and testing with potential implications to patient management. Here we briefly review APS pathophysiology, strengths and weaknesses of classification criteria, laboratory challenges leading to test interpretation, and clinical management of this complex condition.

Keywords: ISTH; antiphospholipid antibodies; antiphospholipid syndrome; lupus anticoagulant; thrombosis.

Figure 1.

The pathophysiology of antiphospholipid syndrome.^–

Figure 2.

Historical milestones in the recognition and diagnosis of antiphospholipid syndrome.^,–

Figure 3.

The coagulation cascade, coagulation tests and sites of action of anticoagulant therapy.^,–

Figure 4.

Comparison of 2009 and 2020 ISTH lupus anticoagulant testing algorithms.^,