Current management of catastrophic antiphospholipid syndrome

The catastrophic variant of the antiphospholipid syndrome (APS) is the most severe form and is characterized by clinical evidence of multiple organ involvement developing over a short period of time, histopathological evidence of small vessel occlusions and laboratory confirmation of antiphospholipid antibodies (aPL) as assessed in 2003 in the international consensus statement on the classification criteria for this condition [1]. Recently, our group has updated the diagnostic algorithms of catastrophic APS in a step-by-step approach [2]. Data such as previous history of APS or persistent aPL positivity, the number of organs involved by thrombosis developing in less than a week, the biopsy diagnosis of microthrombosis, and finally, other explanations for multiple organ thromboses and/or microthrombosis should be considered in the diagnostic approach. From the pathophysiologic point of view, catastrophic APS is a thrombotic microangiopathic condition, characterized by a diffuse thrombotic microvasculopathy with a predilection for the lungs, brain, heart, kidneys, skin and GI tract [3]. Another specific characteristic of catastrophic APS is that 60% of patients appear to have a triggering factor, especially infections (present in up to 25% of cases), anticoagulation withdrawal or following a surgical procedure, a biopsy in patients with neoplasia or immunizations [3]. However, the reasons as to why a minority of patients with aPL develop a multiorgan failure syndrome are unknown. At present, there are no studies on the pathophysiological mechanisms of catastrophic APS. Theoretically, there are two possible explanations of the clinical manifestations of catastrophic APS: first, the vascular occlusions in these patients might be themselves responsible for the ongoing thrombosis, as clots continue to generate thrombin, fibrinolysis is depressed and there is consumption of the natural anticoagulant proteins [4]; second, the manifestations of the systemic inflammatory response syndrome (SIRS), which are presumed to be due to excessive cytokine release from affected and necrotic tissues [5]. Which are the main causes of mortality of patients with catastrophic APS? Among the first 250 patients included in the website-based international registry of patients with catastrophic APS (CAPS Registry; freely accessed at [101]), 114 (46%) died at the time of the catastrophic APS event, which was identified as the cause of death in 80 of them. Cerebral involvement was the most frequent cause of death (27.2%), followed by cardiac involvement (19.8%), infection (19.8%) and multiorgan failure (17.3%) (Table 1) [6]. In other words, almost half of the patients died due to thrombotic events such as stroke or to SIRS such as acute respiratory distress syndrome or encephalopathy [7]. The current treatment of catastrophic APS is based on this empirical pathogenic basis. Besides identification and treatment of any precipitating factor, first-line therapies should always include the combination of anticoagulation against thrombosis plus glucocorticoids against manifestations of SIRS plus plasma exchange and/or The catastrophic variant of the antiphospholipid syndrome (APS) is the most severe form of APS with acute multiple organ involvement and small vessel thrombosis. At present, there are no studies on the pathophysiological mechanisms of catastrophic APS. The two theoretical explanations for the clinical manifestations of catastrophic APS are the development of thrombosis and the systemic inflammatory response syndrome (SIRS). From retrospective study data, first-line therapies should always include the combination of anticoagulation against thrombosis plus glucocorticoids against manifestations of SIRS plus plasma exchange and/or intravenous immunoglobulins to remove or block the antiphospholipid antibodies and cytokines involved in the SIRS. This review is focused on current management of catastrophic APS and some of the potential new therapeutic approaches.