Catastrophic antiphospholipid syndrome: how to diagnose a rare but highly fatal disease

Abstract

Antiphospholipid syndrome (APS) is a multisystem autoimmune condition characterized by vascular thromboses and/or pregnancy loss associated with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS (CAPS) is the most severe form of APS with multiple organ involvement developing over a short period of time, usually associated with microthrombosis. 'Definite' and 'probable' CAPS have been defined based on the preliminary classification criteria; however, in a real-world setting, aPL-positive patients with multiple organ thromboses and/or thrombotic microangiopathies exist who do not fulfill these criteria. Previous APS diagnosis and/or persistent clinically significant aPL positivity is of great importance for the CAPS diagnosis; however, almost half of the patients who develop CAPS do not have a history of aPL positivity. The purpose of this paper is to summarize the diagnostic challenges and the recently updated diagnostic algorithms for CAPS providing a 'step-by-step' approach for clinicians (and researchers) in the assessment of patients with multiple organ thromboses.

Keywords: anti-β2-glycoprotein-1 antibody; anticardiolipin antibody; antiphospholipid syndrome; catastrophic antiphospholipid syndrome; lupus anticoagulant; thrombosis.

Algorithm A.

Catastrophic antiphospholipid syndrome (CAPS) diagnosis in patients with history of antiphospholipid syndrome (APS) or persistent antiphospholipid antibody (aPL) positivity [Erkan et al. 2010]. Reprinted from [Erkan et al. 2010] with permissions from Elsevier. *Our recommendation for the definition of ‘positive aPL’ is: lupus anticoagulant (LA) test positive based on the guidelines of International Society of Thrombosis and Haemostasis [Pengo et al. 2009]; anticardiolipin antibody (aCL) IgG/M ≥40 U, and/or anti-β₂-glycoprotein-I antibody (aβ2GPI) IgG/M ≥40 U. Caution and further assessment(s) are required if: (a) LA test is performed in anticoagulated patients; (b) aCL or aβ2GPI IgG/M titers are in the range of 20–39 U; and/or (c) aCL or aβ2GPI IgA is the only positive aPL enzyme-linked immunosorbent assay (ELISA) test.

Algorithm B.

Catastrophic antiphospholipid syndrome (CAPS) diagnosis in patients without history of antiphospholipid syndrome (APS) or persistent antiphospholipid antibody (aPL) positivity [Erkan et al. 2010]. Reprinted from [Erkan et al. 2010] with permissions from Elsevier. *Our recommendation for the definition of ‘positive aPL’ is: lupus anticoagulant (LA) test positive based on the guidelines of International Society of Thrombosis and Haemostasis [Pengo et al. 2009]; anticardiolipin antibody (aCL) IgG/M ≥40 U, and/or anti-β₂-glycoprotein-I antibody (aβ2GPI) IgG/M ≥40 U. Caution and further assessment(s) are required if: (a) LA test is performed in anticoagulated patients; (b) aCL or aβ2GPI IgG/M titers are in the range of 20–39 U; and/or (c) aCL or aβ2GPI IgA is the only positive aPL enzyme-linked immunosorbent assay (ELISA) test. **‘Positive aPL’ twice 12 weeks apart (of note, the original Sapporo APS classification criteria required two positive aPL tests 6 weeks apart [Wilson et al. 1999], which has been changed to 12 weeks as part of the updated Sapporo APS classification criteria [Miyakis et al. 2006].

Algorithm C.

Catastrophic antiphospholipid syndrome (CAPS) diagnosis in patients without history of antiphospholipid syndrome (APS) or persistent antiphospholipid antibody (aPL) positivity [Erkan et al. 2010]. Reprinted from [Erkan et al. 2010] with permissions from Elsevier. *Our recommendation for the definition of ‘positive aPL’ is: lupus anticoagulant (LA) test positive based on the guidelines of International Society of Thrombosis and Haemostasis [Pengo et al. 2009]; anticardiolipin antibody (aCL) IgG/M ≥40 U, and/or anti-β₂-glycoprotein-I antibody (aβ2GPI) IgG/M ≥40 U. Caution and further assessment(s) are required if: (a) LA test is performed in anticoagulated patients; (b) aCL or aβ2GPI IgG/M titers are in the range of 20–39 U; and/or (c) aCL or aβ2GPI IgA is the only positive aPL enzyme-linked immunosorbent assay (ELISA) test. **‘Positive aPL’ twice 12 weeks apart (of note, the original Sapporo APS classification criteria required two positive aPL tests 6 weeks apart [Wilson et al. 1999], which has been changed to 12 weeks as part of the updated Sapporo APS classification criteria [Miyakis et al. 2006].