Proposed 2-hit model for CAPS. We propose a pathogenic model in which aPLs induce complement activation and cause thrombosis. Patients who also have a pathogenic loss-of-function mutation in a complement inhibitory factor (CFH, CFI, CD46 [MCP], THBD, CR1) or a gain-of-function mutation of a complement-activating factor (CFB, C3) are likely to be predisposed to uncontrolled complement activation, which could lead to disseminated thrombosis and ischemic multiorgan failure in the setting of a complement-amplifying trigger, such as infection, surgery, or autoimmune disease.