Catastrophic Antiphospholipid Syndrome: A Review of Current Evidence and Future Management Practices

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by blood clots and pregnancy complications due to antiphospholipid antibodies. Catastrophic APS (CAPS), a severe variant, leads to multiorgan failure and is often fatal. Pathogenesis involves antiphospholipid antibodies, particularly anti-beta-2-glycoprotein I (aβ2GPI), which trigger endothelial cell (EC) activation, cytokine release, and a prothrombotic state. Infections, surgeries, and other triggers can precipitate CAPS, leading to widespread microthromboses and systemic inflammatory responses. CAPS predominantly affects younger patients and those with systemic lupus erythematosus (SLE), with a high mortality rate, though recent treatment advances have improved survival. Diagnosing CAPS involves identifying clinical manifestations, including rapid organ involvement and small vessel occlusions, confirmed by histopathology and high antiphospholipid antibody levels. The CAPS registry data indicate that commonly affected organs include kidneys, lungs, central nervous system, and the heart, with a high prevalence of lupus anticoagulant and anticardiolipin antibodies (aCL). Current management strategies focus on therapeutic anticoagulation, immunosuppressive therapies like corticosteroids, and adjunct treatments such as plasmapheresis and intravenous immunoglobulin (IVIG). Early use of glucocorticoids and combination therapy has significantly improved outcomes. In life-threatening cases, especially with microangiopathy, experts recommend performing plasma exchange (PE). Patients with associated autoimmune conditions or refractory cases may receive cyclophosphamide (CY) and rituximab while considering PE for treatment. Maintenance of anticoagulation with an appropriate international normalized ratio (INR) is crucial to prevent recurrence. This article reviews the pathogenesis and epidemiology of CAPS. It also examines the current management strategies, and discusses the challenges and controversies associated with these strategies. It hereafter offers recommendations for future management and outlines directions for further research.

Keywords: anti coagulation; antiphospholipid antibody syndrome; blood clots; catastrophic antiphospholipid syndrome; multiorgan system failure; thrombosis.

Figure 1. Effects of aPLA on the complement system, inflammation, and vascular tone. Black arrows indicate the direction of change: downward for a decrease and upward for an increase [6].

aPLA diminishes eNOS activity through its interaction with ApoER2, resulting in decreased NO production. This reduction in NO leads to impaired vasodilation and endothelial dysfunction. Additionally, aPLA triggers the activation of TLR and inflammasome pathways, promoting the release of inflammatory cytokines and chemokines. On the cell surface, aPLA also activates the complement system, culminating in coagulation activation and cell damage due to C5b-9 deposition. β2GPI: Beta-2-glycoprotein I, ApoER2: Apolipoprotein E2 receptor; DAB2: Disabled-2; PP2A: Protein phosphatase 2A; eNOS: Nitric oxide synthase; sENG: Soluble endoglin; TLR: Toll-like receptor; TLT-8: Toll-like receptor 8; aPLA: Antiphospholipid antibodies; NO: Nitric oxide