In fact, oxidized extracellular hemoglobin cause direct oxidative damage to myelin components, specifically to MBP (Bamm et al

In fact, oxidized extracellular hemoglobin cause direct oxidative damage to myelin components, specifically to MBP (Bamm et al., 2017). APS. Prompt and accurate diagnosis and antiaggregant and anticoagulant treatment of APS could be vital to prevent or at least reduce APS-related morbidity and mortality. Keywords: antiphospholipid syndrome, pathogenesis, MS-like syndrome, thrombosis, vasculopathy Current Difficulties in The Diagnosis and Management of The Antiphospholipid Syndrome The antiphospholipid syndrome (APS) is usually a systemic autoimmune disorder characterized by the presence of peripheral Mal-PEG2-VCP-Eribulin procoagulant autoantibodies together with the occurrence of recurrent thrombosis (venous, arterial or both) and/or pregnancy morbidity and fetal loss (Miyakis et al., 2006). Mal-PEG2-VCP-Eribulin The sole presence of autoantibodies does not usually lead to thrombosis. APS can indeed be caused by a diverse array of antiphospholipid (aPL) antibodies that identify cell surface proteins linked to phospholipids as non self within a pro-inflammatory context that has been described as a second hit (after contamination or tissue damage). This combined effect would in turn activate the clotting cascade in a wide variety of mechanisms that lead to the development of thrombosis (Giannakopoulos and Krilis, 2013; Meroni et al., 2018). The routine diagnostic aPL antibodies, used according to the 2006 Sydney revised APS classification criteria, are anticardiolipin (aCL), anti2-glycoprotein-I (a2GPI) and lupus anticoagulant (LA). The non-classic aPL antibodies include anti-phosphatidylserine (aPS), anti-phosphatidylserine-2GPI (aPS-2), anti-phosphatidylethanolamine (aPE), anti-prothrombin-prothrombin complex (aPT-PT), anti-phosphatidylserine-prothrombin complex (aPS-PT) and anti-annexin V (aAnV; Shoenfeld et al., 2008). According to Sydney revision, classification of APS requires at least one clinical manifestation of vascular thrombosis or obstetrical events and the presence of at least two positive laboratory criteria (aCL IgG or IgM and/or a2GPI IgG or IgM at moderate titers and/or LA positivity) on two individual occasions at least 12 weeks apart (Miyakis et al., 2006). Persistence of positive aPL was launched in order to differentiate the aPL antibodies appearing in the setting of infections or other unspecific Rabbit Polyclonal to ARG1 conditions, in which aPL are transient and non-thrombogenic. Indeed, it is also well known that aPL antibodies fluctuate in blood, which hampers their interpretation (Donohoe et al., 2002; Fonseca and DCruz, 2008). To make the picture more complicated, besides the well-recognized obstetric and thrombotic hallmarks, APS can encompass an exceedingly variable clinical spectrum of multiorgan non-thrombotic manifestations, in the so called extra-criteria or non-criteria manifestations. Among these are the neurological manifestations, such as epilepsy, myelitis, chorea and migraine; hematological manifestations, such as thrombocytopenia and hemolytic anemia; livedo reticularis; pulmonary and Mal-PEG2-VCP-Eribulin osteoarticular manifestations; valvular heart disease; and nephropathy, to mention a few examples that cannot be exclusively explained by prothrombotic phenomena (Gmez-Puerta and Cervera, 2014; Negrini et al., 2017; Garcia and Erkan, 2018). In addition, the extra-criteria manifestations, as well as the classical ones, can occur in the setting of APS without fulfilling the serological criteria, as for instance with low titers aCL or a2GPI antibodies (Cobo-Soriano et al., 1999; Micheloud et al., 2005) or even in the absence of detectable aPL in the so-called seronegative APS. APS may be diagnosed as an isolated disease (main APS) or associated to other autoimmune disorders, mainly systemic lupus erythematous (SLE), rheumatoid arthritis, Sj?gren syndrome, autoimmune thyroid disease, systemic sclerosis, systemic vasculitis, dermatopolymyositis, primary biliary cirrhosis and autoimmune hepatitis. It has been estimated that approximately 50% of patients who suffer from APS will develop SLE (Salmon et al., 2007). Nowadays, because of potentially recurrent thrombosis and the hypercoagulability scenario, there is consensus in treating APS patients with long-term oral anticoagulants and, in order to prevent obstetric manifestations, with Mal-PEG2-VCP-Eribulin a combination of low dose aspirin Mal-PEG2-VCP-Eribulin and low molecular excess weight heparin (LMWH;Empson et al., 2005). There is a heated argument around the clinically significant titers of aPL antibodies. Investigators are strongly advised to classify patients as affected by APS, when more than one laboratory criterion is present alone or in combination. Specifically, LA presence in plasma; medium or high titer of IgG and/or IgM aCL antibody in serum or plasma (i.e., >40 GPL or MPL, or >the 99th percentile); IgG and/or IgM a2GPI antibody in serum or plasma (in titer >the 99th percentile; Miyakis et al., 2006). Growing evidences claim to consider the clinical impact of low level positive aPL antibodies and the necessity to set new cut-off levels, basicallythough not exclusivelyin obstetric APS (Devreese et.

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