Regular articlePlatelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies☆
Introduction
The antiphospholipid syndrome (APS) is defined by one or more episodes of thrombosis or unexplained pregnancy loss in association with persisting positive antiphospholipid antibodies (APLA), either anti-cardiolipin (aCL), anti-β2GPI (aβ2GPI), and/or lupus anticoagulant (LAC) [1], [2], [3], [4], [5], [6]. APS is frequently associated with underlying autoimmune disorders, most commonly systemic lupus erythematosus (SLE), known as secondary APS, but no underlying disorder is identified in primary APS. In its most severe and life-threatening form, it is called catastrophic APS.
Ever since the identification of APS by Hughes in 1985 [7], the mechanism or target of injury underlying the thrombotic events has been vigorously debated. The leading candidates for target of APLA-induced injury have been either platelets [8], [9], [10], [11], [12] or the vascular endothelial cells (EC) [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], or both [27], [28], [29], [30], [31], [32]. Among the many mechanisms proposed, interference with the protein C anticoagulant system has often been proposed [30], [33], [34], [35], [36], along with activation of complement [37], [38], and other hypotheses in the references cited above. However, the ultimate effect responsible for thrombosis in most scenarios is believed to be platelet activation and/or endothelial injury [31]. Each of these and other proposed mechanisms of APLA-induced thrombosis (or targets of tissue injury) is supported by some clinical and laboratory evidence but no broad consensus has yet been reached. Closely related to these unsolved problems are why so many patients who are chronically positive for APLA or LAC remain free of thrombosis.
The present study was undertaken with the aim of evaluating the relative extents of platelet and endothelial activation in APLA-positive patients, with and without thrombosis. In this study, activation of platelets is measured by marker CD62P as well as by platelet microparticles (PMP), while endothelial activation is measured by endothelial microparticles (EMP) [39], [40].
Section snippets
Patient population
Under a protocol approved by the Institutional Review Board at this medical center, a total of 88 patients were consecutively identified during a two-year period who were persistently APLA-positive (on two or more occasions at least 6 weeks apart) by the methods given below. Of this total, 60 had a history of thrombosis (24 with venous thrombosis, 30 with arterial thrombosis, and 6 with both). Patients with history of miscarriage were excluded. All blood samples were collected at least 8 weeks
Results
Data on the two patient groups, thrombotic (T) and non-thrombotic (non-T), both of which were all positive for APLA, is shown in Table 1. They are of nearly equal mean ages, gender ratios, and proportion with primary APLA. Many or most subjects had other underlying conditions but there was no significant difference in these respects between the two groups.
Results of solid-phase (ELISA) assay of APLA are summarized in Table 2 in terms of frequency of positives. There are no significant
Discussion
The principal aim of this study was to seek to differentiate between APLA-positive patients with vs. without thrombosis. No difference was found in levels of the endothelial activation marker, EMP, between the T and non-T groups. Although both groups exhibited elevated EMP with respect to normal controls, there was no difference between the groups in this measure. This shows that chronic endothelial activation is characteristic of positive APLA, whether or not thrombosis is present.
In contrast,
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2016, Autoimmunity ReviewsA new cytofluorimetric approach to evaluate the circulating microparticles in subjects with antiphospholipid antibodies
2015, Thrombosis ResearchCitation Excerpt :So, using this approach and comparing the APS patients with the healthy donors, we observed, in agreement with previous observations [3,30] a significant increased number of total MPs, and in detail of PMPs and EMPs subsets. Recent studies have already highlighted increased levels of PMPs and EMPs in the plasma of aPL positive subjects [2,3,12,31]. But, in this study we have subdivided the patients in two main groups: the APS and the carriers (aPL-positive subjects without the clinical APS criteria) and, for the first time, we observed an increase in the number of all subpopulations of MPs in aPL carriers compared to healthy controls, and also, in APS compared to carriers.
Endothelial and platelet microparticles in patients with antiphospholipid antibodies
2015, Thrombosis ResearchCitation Excerpt :In addition, patients with aPL associated thrombotic complications had significantly higher levels of platelet microparticles but those with obstetric complications and isolated aPL did not. Previous studies of platelet microparticles in patients with APS have failed to show any difference in levels of platelet microparticles in patients with APS compared to controls [13,16–18]. However, although this was the case in the study by Jy et al. [16], when they performed subgroup analysis, they showed elevated platelet microparticle levels in patients with thrombotic complications of aPL.
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This work is supported largely by the Wallace H. Coulter Foundation.