Catastrophic APS is a potentially life-threatening condition with a high mortality, which requires high clinical awareness. New mechanisms for its production can only be explored if samples are obtained, stored, and dis-patched to investigation sites in Europe (Barcelona), the United States (Atlanta), and Japan (Sapporo). Details will be posted and made available on the International Registry Web Site in 2006. It is essential that the condition be diagnosed early and treated aggressively. The combination of high doses of iv heparin, iv steroids plus repeated doses of iv gammaglobulins or plasma exchange is the treatment of choice in patients with this severe condition. Additionally, preventive measures in patients with APS may be effective if the development of the catastrophic APS is to be avoided.