Similar evidence in the treatment of primary APS is limited to case reports or case series, and studies on a large scale lack. the possible role of immunomodulation in primary APS to provide a broad overview of potentially safe and effective target treatments for managing this devastating disease. Keywords: antiphospholipid syndrome, lupus anticoagulant, anticardiolipin, anti-2-glycoprotein I, catastrophic antiphospholipid syndrome 1. Introduction JK 184 The antiphospholipid syndrome (APS) is characterized by the development of venous and/or arterial thrombosis and pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL), including lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-2 glycoprotein-I (2GPI) antibodies [1]. According to the revised Sydney (or Sapporo) criteria for the classification of true APS, aPL should be detected on at least two occasions, with testing completed 12 or more weeks apart [2]. The APS may be classified in primary APS (PAPS) and secondary antiphospholipid syndrome (SAPS), i.e., APS occurring in the context of another medical condition [1]. Indeed, the presence of aPL may be associated with other conditions such as autoimmune diseases, mainly JK 184 systemic lupus erythematosus (SLE) [3], occasionally infections [4], drugs [3], and malignancies [5]. Prevalence of the aPL in the general population ranges between 1 and 5% [1], whereas in autoimmune disease, particularly SLE, the prevalence is as high as 30% [3]. APS clinical manifestations could vary from asymptomatic carriers to life-threatening forms characterized by the rapid development of microthrombosis leading to rapid multiple organ failure [1]. Hallmark features of APS are venous and/or arterial thromboembolic events (TEs) and pregnancy morbidity [6]. TEs result in vascular occlusions; the most common types of venous thrombosis include deep vein thrombosis and pulmonary embolism, while strokes and transient ischemic attacks are the most common arterial thrombosis [6,7]. Non-thrombotic events include thrombocytopenia, hemolytic anemia, arthralgia, arthritis, cardiac valve disease, nephropathy, livedo reticularis, migraine, chorea, and epilepsy [1]. These events are also known as non-criteria manifestations. According to The Euro-Phospholipid Project [8], which described the baseline characteristics of a cohort of 1000 patients with APS, early fetal losses (<10 weeks) seem to be more frequent (35.4%) than late fetal losses (10 weeks) (16.9%). Obstetric manifestations described in APS are pre-eclampsia, eclampsia, and abruptio placentae [4]. Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of APS occurring in about 1% of cases [9]. It manifests as microangiopathy and affects small vessels of multiple organs, resulting in organ failure [10]. It has been hypothesized that CAPS may be due to the development of systemic inflammatory response syndrome (SIRS), probably due to excessive cytokine release from injured tissues [8]. Infection, surgery, pregnancy, and puerperium are identified triggers of CAPS [11,12]. CAPS-first line therapies include the association of anticoagulation, glucocorticoids, plasma exchange, and/or intravenous immunoglobulins (IVIGs) [13]. Treatment strategies for the management of APS can be differentiated in primary thrombo-prophylaxis in patients with persistent aPL with no prior JK 184 TEs, and secondary thrombo-prophylaxis, in patients with previous TEs [14,15]. Regarding primary thrombo-prophylaxis, it is essential to underline that not all individuals with high levels of aPL develop thrombosis [15]. Factors that should be taken into account when assessing the risk of TEs are the concomitance of other risk factors for thrombosis and for cardiovascular diseases, the presence of other autoimmune conditions, and the Nr2f1 multiple positivity of aPL [15]. Indeed, Pengo et al. reported that multiple positivity of aPL is more frequently associated with TEs than a single test positivity. The triple-positive population of LA, aCL, and anti-2GPI has been regarded as the highest risk group for TEs and JK 184 poor neonatal outcomes [16,17]. The authors also showed that in their population TEs were more frequent among.
Similar evidence in the treatment of primary APS is limited to case reports or case series, and studies on a large scale lack
