Triple Antiphospholipid Antibody Positivity Research Articles

ARID5B-mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3/STAT3 complex in β2GPI/anti-β2GPI-treated monocytes.

Alterations of the trimethylation of histone3lysine 4 (H3K4me3) mark in monocytes are implicated in the development of autoimmune diseases. Therefore, the purpose of our study was to elucidate the role of H3K4me3-mediated epigenetics in the pathogenesis of antiphospholipid syndrome (APS). H3K4me3 Cleavage Under Targets and Tagmentation and Assay for Transposase-Accessible Chromatin were performed to determine the epigenetic profiles. Luciferase reporter assay, RNA immunoprecipitation, RNA pull-down, co-immunoprecipitation and chromatin immunoprecipitation were performed for mechanistic studies. Transmission electron microscopy and propidium iodide staining confirmed cell pyroptosis. Primary monocytes from patients with primary APS (PAPS) and healthy donors were utilised to test the levels of key molecules. A mouse model mimicked APS was constructed with beta2-glycoprotein I (β2GPI) injection. Blood velocity was detected using murine Doppler ultrasound. H3K4me3 signal and open chromatin at the ARID5B promoter were increased in an in vitro model of APS. The epigenetic factor ARID5B directly activated LINC01128 transcription at its promoter. LINC01128 promoted the formation of the BTF3/STAT3 complex to enhance STAT3 phosphorylation. Activated STAT3 interacted with the NLRP3 promoter and subsequently stimulated pyroptosis and apoptosis. ARID5B or BTF3 depletion compensated for LINC01128-induced pyroptosis and apoptosis by inhibiting STAT3 phosphorylation. In mice with APS, β2GPI exposure elevated the levels of key proteins of pyroptosis and apoptosis pathways in bone marrow-derived monocytes, reduced the blood velocity of the ascending aorta, increased the thrombus size of the carotid artery, and promoted the release of interleukin (IL)-18, IL-1β and tissue factor. Patients with PAPS had the high-expressed ARID5B and LINC01128, especially those with triple positivity for antiphospholipid antibodies. Moreover, there was a positive correlation between ARID5B and LINC01128 expression. This study indicated that ARID5B/LINC01128 was synergistically upregulated in APS, and they aggravated disease pathogenesis by enhancing the formation of the BTF3/STAT3 complex and boosting p-STAT3-mediated pyroptosis and apoptosis, thereby providing candidate therapeutic targets for APS. The H3K4me3 mark and chromatin accessibility at the ARID5B promoter are increased in vitro model mimicked APS. ARID5B-mediated LINC01128 induces pyroptosis and apoptosis via p-STAT3 by binding to BTF3. ARID5B is high- expressed in patients with primary APS and positively correlated with LINC01128 expression. OICR-9429 treatment mitigates pyroptosis and related inflammation in vivo and in vitro models mimicked APS.

Arterial thrombosis triggered by methotrexate-induced hyperhomocysteinemia in a systemic lupus erythematosus patient with antiphospholipid antibodies

Systemic lupus erythematosus (SLE) patients have an increased risk of cardiovascular disease and thrombotic events, and the presence of antiphospholipid antibodies further raises the risk of these complications. Here we report a case of a patient with SLE and triple positivity for antiphospholipid antibodies who developed a popliteal artery thrombosis in the context of a severe hyperhomocysteinemia after the introduction of methotrexate (MTX) treatment. MTX is one of the most prescribed medications for a wide spectrum of autoimmune diseases, including SLE. On the other hand, by interfering with folate metabolism, it may induce hyperhomocysteinemia, which, in turn, may increase the risk of vascular complications. Current recommendations suggest screening and, when possible, treating classical and disease-related cardiovascular risk factors in all lupus patients. Based on what observed in our case, we suggest a follow-up of homocysteine levels after the introduction of drugs capable of inducing hyperhomocysteinemia, such as MTX, in SLE patients at high cardiovascular risk.

Pulmonary involvement in catastrophic antiphospholipid syndrome: A descriptive analysis from the “CAPS Registry”

ObjectivesTo describe the pulmonary involvement in patients with catastrophic antiphospholipid syndrome (CAPS), focusing on its relationship with extrapulmonary involvement, laboratory, radiological, and pathological findings. MethodsThis retrospective cross-sectional study includes all patients grouped in the “CAPS Registry”. All cases were reviewed, and those with pulmonary thromboembolism (PE) and/or diffuse alveolar hemorrhage (DAH) were selected. Data on pulmonary and extrapulmonary clinical presentation, radiologic patterns, laboratory findings, associated autoimmune diseases, treatments, and outcomes were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test, while T-test for independent variables was used to compare groups regarding continuous variables. IBM-SPSS v.22 was used for data analysis. ResultsPE was reported in 129 (48.6 %) episodes, DAH in 75 (28.3 %) episodes, and overlap (DAH plus PE) in 7 (2.6 %) episodes. Bronchoalveolar lavage (BAL) was performed in 35 (4.9 %) CAPS episodes, and lung pathology samples were obtained in 84 (10.5 %) episodes (including autopsies). A significant relationship was observed between DAH and laboratory features of thrombotic microangiopathy (TMA). A meaningful relationship was also found between triple antiphospholipid antibody positivity and pathological TMA (26.5 %) as well as hypocomplementemia and DAH (24 %). ConclusionsPulmonary involvement may include both TMA and non-thrombotic inflammation, which can be differentiated into three patterns: PE, DAH with systemic TMA with hypocomplementemia or DAH without systemic TMA with/without hypocomplementemia.

OA04 Paediatric APS - children are not just small adults

OA04 Paediatric APS - children are not just small adults

Clinical and therapeutic value of the adjusted Global Antiphospholipid Syndrome Score in primary obstetric antiphospholipid syndrome.

(1) To assess the clinical utility of the adjusted global antiphospholipid syndrome score (aGAPSS) to predict new obstetric events during follow-up in primary obstetric antiphospholipid syndrome (POAPS) patients under standard-of-care treatment (SC) based on the use of low-dose aspirin (LDA) + heparin and (2) to study the risk of a first thrombotic event and to evaluate whether stratification according to this score could help to identify POAPS patients who would benefit from long-term thromboprophylaxis. This is a retrospective, multicentre study. 169 women with POAPS were evaluated for the presence of a new obstetric event and/or a first thrombotic event during follow-up [time period: 2008-2020, median: 7years (6-12years)]. The outcomes of 107 pregnancies from these POAPS patients with SC were studied to evaluate relapses. Simple and multivariable logistic regression analyses were performed. Regarding obstetric morbidity, only triple positivity for antiphospholipid antibodies (aPLs) [OR = 8.462 (95% CI: 2.732-26.210); p < 0.0001] was found to be a strong risk factor independently associated with treatment failure. On the other hand, triple positivity for aPLs [OR=10.44 (95% CI: 2.161-50.469), p = 0.004] and an aGAPSS ≥7 [OR = 1.621 (95% CI: 1.198-2.193), p = 0.002] were independent risk factors associated with a first thrombotic event. LDA was marginally associated with a decrease in the risk of thrombosis only in patients with aGAPSS ≥ 7 (p = 0.048). aGAPSS appears to be useful in predicting the occurrence of a first thrombotic event in POAPS patients, and these stratification of patients could be helpful in selecting patients who would benefit from thromboprophylaxis with LDA.

The Identification of High Risk APS Patients for Thrombosis with Triple Antiphospholipid Antibody Positivity Is Platform Dependent

The antiphospholipid syndrome (APS) is characterized by thrombosis and/or specific pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPL). Laboratory criteria include aPL detection by a functional assay referred to as lupus anticoagulant (LAC) or by quantitative solid phase assays measuring anti-β2glycoprotein I (aβ2GPI) and anti-cardiolipin (aCL) IgG/IgM antibodies. Triple positivity (i.e. positivity for LAC, aCL and aβ2GPI antibodies irrespective of the isotype) is associated with a high risk for both a first thrombotic event and recurrence. For these high-risk triple positive patients, a repetitive aPL measurement proved not to be required. Reports from external quality control programs illustrate that commercially available aPL assays produce variable results, probably originating from differences in assay design, epitope exposure and a lack of standardization. On the contrary, the detection of triple positivity was recently suggested to be method and platform independent. In a large multicentre study, we aimed to investigate the variability in triple positivity detection and its clinical association between different aPL platforms.In this study we included 853 patients from seven European medical centers. Patients were classified by the local centers resulting in 259 thrombotic APS patients, 204 diseased controls for thrombosis, 196 patients with autoimmune diseases other than APS and 194 patients without any clinical and laboratory criteria for APS. Four platforms, ACL AcuStar (Instrumentation Laboratory, Bedford, MA, USA), Bioplex 2200 (Bio-Rad Laboratories, Hercules, CA, USA), ImmunoCap EliA (ThermoFisher (Phadia), Waltham, MA, USA) and QUANTA Lite ELISA (Inova Diagnostics, San Diego, CA, USA), were selected based on frequency of use and the willingness of manufacturers to provide their assays. All samples with all assays were tested at one location by a single technician. Lupus anticoagulant positivity was determined by the local center, according to the ISTH guidelines.From the 259 patients diagnosed with thrombotic APS, 202 were positive for LAC. Detection of triple positivity proved to be variable between platforms: 118, 101, 111 and 89 detected with Bioplex, ImmunoCap EliA, AcuStar and QUANTA Lite respectively. To investigate the diagnostic efficacy of triple positivity of the different platforms, we calculated the sensitivity, specificity and odds ratio (OR) for thrombosis. The sensitivity of triple positivity for thrombosis was low and varied from 19% up to 26% between the tested platforms (Figure 1A). However, a high specificity for thrombosis with minor variation from the platforms was obtained ranging from 93% up to 96% (Figure 1A). Looking at the OR for thrombosis, triple positivity was significantly correlated with thrombosis independent of the platform used (Figure 1B). However, the OR for thrombosis ranged from 4.2 up to 5.2 for the different platforms used to detect aβ2GPI and aCL aPL.Taken together, our study confirmed the high-risk profile for thrombosis associated with triple positivity, independent of the platform used to detect aβ2GPI and aCL aPL. Contrary, the number of triple positives is dependent on the platform used, resulting in varying sensitivities of triple positivity for thrombosis over the different platforms. The high risk on recurrent clinical complications in triple positive APS patients often requires them to take indefinite oral anticoagulant treatment. Therefore, to avoid misclassification of high-risk APS patients, standardization/uniformity of solid phase assays for the diagnosis of APS is urgently warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Independent association of low IFNλ1 gene expression and type I IFN score/IFNλ1 ratio with obstetric manifestations and triple antiphospholipid antibody positivity in primary antiphospholipid syndrome

Recent data suggest an important role of type I interferons (IFN) in antiphospholipid syndrome (APS). Here we aimed to evaluate the interplay of type I and type III (or IFNλs) IFNs in APS and potential clinical and serological associations. Our findings suggest that patients with primary APS (PAPS) and systemic lupus erythematosus (SLE)/APS displayed increased type I IFN scores but decreased IFNλ1 gene expression levels compared to healthy individuals, as assessed with real-time qPCR analysis in isolated peripheral blood mononuclear cells (PBMCs). Type I IFN score/IFNλ1 ratio was remarkably higher in patients with PAPS and SLE/APS as well as in SLE patients with or without antiphospholipid antibodies (aPL) vs controls. In conclusion, our results reveal an association between low IFNλ1 expression and obstetric APS. Moreover, the type I IFN score/IFNλ1 ratio seems to be a potential marker of high risk APS given its associations with triple aPL positivity.

Beyond thrombosis: Anti-β2GPI domain 1 antibodies identify late pregnancy morbidity in anti-phospholipid syndrome

Antibodies against β2 glycoprotein I (anti-β2GPI) have been identified as the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the most relevant epitope is a cryptic and conformation-dependent structure on β2GPI domain (D) 1. Anti-β2GPI domain profiling has been investigated in thrombotic APS, leading to the identification of antibodies targeting D1 as the main subpopulation. In contrast, scarce attention has been paid to obstetric APS, hence this study aimed at characterizing the domain reactivity with regards to pregnancy morbidity (PM).To this end, 135 women with persistently positive, medium/high titre anti-β2GPI IgG, without any associated systemic autoimmune diseases and at least one previous pregnancy were included: 27 asymptomatic carriers; 53 women with obstetric APS; 20 women with thrombotic APS; and 35 women with both thrombotic and obstetric complications. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a research ELISA assay, respectively (QUANTA Flash® β2GPI Domain 1 IgG and QUANTA Lite® β2GPI D4/5 IgG, Inova Diagnostics).Positivity for anti-D1 antibodies, but not anti-D4/5 antibodies, was differently distributed across the 4 subgroups of patients (p < 0.0001) and significantly correlated with thrombosis (χ2 = 17.28, p < 0.0001) and PM (χ2 = 4.28, p = 0.039). Patients with triple positivity for anti-phospholipid antibodies displayed higher anti-D1 titres and lower anti-D4/5 titres compared to women with one or two positive tests (p < 0.0001 and p = 0.005, respectively). Reactivity against D1 was identified as a predictor for PM (OR 2.4, 95% confidence interval [CI] 1.2–5.0, p = 0.017); in particular, anti-D1 antibodies were predictive of late PM, conveying an odds ratio of 7.3 (95% CI 2.1–25.5, p = 0.022). Positivity for anti-D1 antibodies was not associated with early pregnancy loss. Anti-D4/5 antibodies were not associated with clinical APS manifestations.As a whole, our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis, but also with late PM, while positive anti-D4/5 antibodies are not predictive of thrombosis or PM.

Use of factor Xa inhibitors in antiphospholipid antibodies syndrome: A series of seven cases

BackgroundAntiphospholipid syndrome is an autoimmune disease with antibodies against membrane phospholipids with mainly thrombotic and/or obstetric manifestations. Its treatment is generally based on indefinite anticoagulation, usually with warfarin, and which, for various factors, is not always feasible, making it necessary to use alternative therapies. ObjectiveTo describe the experience with rivaroxaban in patients with antiphospholipid syndrome. Materials and methodsA descriptive study was conducted on subjects that met the 2006 Sydney criteria for antiphospholipid antibodies syndrome and received anticoagulation with rivaroxaban at 20mg daily dose in 2reference hospitals in Medellin, Colombia, between January 2012 and April 2015. ResultsThe study included 7 patients, with a mean age of 36±10.8 years (range 23–55). Four patients had venous thrombosis, 5arterial, 5were positive for anticardiolipin antibodies, 3reactive to lupus anticoagulant, 2anti-β2 glycoprotein positive subjects, and one patient had triple antiphospholipid antibody positivity. The median time of warfarin use was 15 months (RIQ 1–36). The reasons for starting rivaroxaban were: bleeding (n=2), sub-therapeutic coagulation ranges (n=2), toxicoderma, gastrointestinal intolerance, and re-thrombosis (n=1, each). The time of use was 17.9±13.4 months (range: 3–34). There were 2recurrent cases of thrombosis during follow-up, and no adverse events. ConclusionThe use of factor Xa inhibitors in a series of patients with antiphospholipid syndrome and unable to use warfarin showed an adequate safety profile; however, 2recurrent episodes of venous thrombosis occurred.

Uso de inhibidores directos del factor Xa en síndrome antifosfolípido: una serie de 7 casos

BackgroundAntiphospholipid syndrome is an autoimmune disease with antibodies against membrane phospholipids with mainly thrombotic and/or obstetric manifestations. Its treatment is generally based on indefinite anticoagulation, usually with warfarin, and which, for various factors, is not always feasible, making it necessary to use alternative therapies. ObjectiveTo describe the experience with rivaroxaban in patients with antiphospholipid syndrome. Materials and methodsA descriptive study was conducted on subjects that met the 2006 Sydney criteria for antiphospholipid antibodies syndrome and received anticoagulation with rivaroxaban at 20mg daily dose in 2reference hospitals in Medellin, Colombia, between January 2012 and April 2015. ResultsThe study included 7 patients, with a mean age of 36±10.8 years (range 23-55). Four patients had venous thrombosis, 5arterial, 5were positive for anticardiolipin antibodies, 3reactive to lupus anticoagulant, 2anti-β2 glycoprotein positive subjects, and one patient had triple antiphospholipid antibody positivity. The median time of warfarin use was 15 months (RIQ 1-36). The reasons for starting rivaroxaban were: bleeding (n=2), sub-therapeutic coagulation ranges (n=2), toxicoderma, gastrointestinal intolerance, and re-thrombosis (n=1, each). The time of use was 17.9±13.4 months (range: 3-34). There were 2recurrent cases of thrombosis during follow-up, and no adverse events. ConclusionThe use of factor Xa inhibitors in a series of patients with antiphospholipid syndrome and unable to use warfarin showed an adequate safety profile; however, 2recurrent episodes of venous thrombosis occurred.

Intracardiac thrombosis in a young female as first presentation of primary antiphospholipid syndrome: A case report

Primary antiphospholipid syndrome (PAPS) is an entity characterized by spontaneous and recurrent abortion and recurrent vascular thromboses (arterial and venous). Intracardiac thrombosis is a rare but life-threatening complication of PAPS. Herein we describe a 21 year-old woman admitted to hospital due to left pleurodynia and shortness of breath with no history of thrombotic events. Helix chest tomography scan disclosed pulmonary embolism as well as a filling defect of the inferior vena cava, which in subsequent cardiac magnetic resonance (MRI) proved to be intracardiac thrombus. Laboratory tests showed triple positivity for antiphospholipid antibodies, renal involvement and thrombocytopenia; PAPS, possibly catastrophic, was diagnosed. The patient was treated with iv pulses of corticosteroids, cyclophosphamide, intravenous immunoglobulin and oral anticoagulation (INR levels between 2.5 and 3), improved gradually and was discharged after 15 days of hospitalization. At 6-month follow-up new cardiac MRI revealed complete resolution of the thrombus. Patients with APS that present with pulmonary embolism should be investigated for the possibility of intracardial thrombus. Indefinite anticoagulation treatment in these patients is warranted due to high recurrence rates.

Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study

The aim of this multicenter study was to assess the present risk of fetal complications and the inherent risk factors in pregnant women with lupus nephritis.Seventy-one pregnancies in 61women (59 Caucasians and 2 Asians) with lupus nephritis were prospectively followed between October 2006 and December 2013. All patients received a counselling visit within 3 months before the beginning of pregnancy and were followed by a multidisciplinary team. At baseline mild active nephritis was present in 15 cases (21.1%).Six pregnancies (8.4%) resulted in fetal loss. Arterial hypertension at baseline (P = 0.003), positivity for lupus anticoagulant (P = 0.001), anticardiolipin IgG antibodies (P = 0.007), antibeta2 IgG (P = 0.018) and the triple positivity for antiphospholipid antibodies (P = 0.004) predicted fetal loss.Twenty pregnancies (28.2%) ended pre-term and 12 newborns (16.4%) were small for gestational age. Among the characteristics at baseline, high SLE disease activity index (SLEDAI) score (P = 0.027), proteinuria (P = 0.045), history of renal flares (P = 0.004), arterial hypertension (P = 0.009) and active lupus nephritis (P = 0.000) increased the probability of preterm delivery. Odds for preterm delivery increased by 60% for each quarterly unit increase in SLEDAI and by 15% for each quarterly increase in proteinuria by 1 g per day. The probability of having a small for gestational age baby was reduced by 85% in women who received hydroxychloroquine therapy (P = 0.023).In this study, the rate of fetal loss was low and mainly associated with the presence of antiphospholipid antibodies. Preterm delivery remains a frequent complication of pregnancies in lupus. SLE and lupus nephritis activity are the main risk factors for premature birth. Arterial hypertension predicted both fetal loss and preterm delivery.Based on our results the key for a successful pregnancy in lupus nephritis is a multidisciplinary approach with close medical, obstetric and neonatal monitoring. This entails: a) a preconception evaluation to establish and inform women about pregnancy risks; b) planning pregnancy during inactive lupus nephritis, maintained inactive with the lowest possible dosage of allowed drugs; c) adequate treatment of known risk factors (arterial hypertension, antiphospholipid and antibodies); d) close monitoring during and after pregnancy to rapidly identify and treat SLE flares and obstetric complications.

Persistent triple antiphospholipid antibody positivity as a strong risk factor of first thrombosis, in a long-term follow-up study of patients without history of thrombosis or obstetrical morbidity.

Introduction The long-term risk of first thrombosis and benefit of prophylaxis in antiphospholipid antibody (aPL) carriers without history of thrombosis or obstetrical morbidity is poorly known. This study aimed to evaluate the long-term rate and risk factors associated with a first thrombosis in those patients. Patients and methods After a prior study ended in December 2005 and was already published, we extended the follow-up period of our cohort of aPL carriers. Results Ninety-eight of the 103 patients of the previous study were included. The annual first thrombosis rate was 2.3% per patient-year during a median of 13 years (6-17). None of the baseline characteristics was predictive of risk of first thrombosis, but persistent aPL over time were associated with an increased risk. The stronger association was found in triple aPL-positive carriers: OR 3.38 (95% CI: 1.24-9.22). Of note, conversely to our previous findings, no benefit of aspirin prophylaxis was observed. Conclusion The risk of first thrombosis in aPL carriers without history of thrombosis or obstetrical morbidity was significant, persisted linearly over time and was associated with persistent aPL. This risk was especially increased in triple aPL-positive carriers, in whom a close follow-up seems to be necessary. Nevertheless, the benefit of aspirin prophylaxis remained unclear.

Histological antiphospholipid-associated nephropathy versus lupus nephritis in patients with systemic lupus erythematosus: an observational cross-sectional study with longitudinal follow-up.

IntroductionRenal involvement is a severe complication in systemic lupus erythematosus (SLE). Moreover, a subset of SLE patients develop the anti-phospholipid syndrome (APS), characterised by the occurrence of anti-phospholipid antibodies in combination with macro- and microvascular thrombotic manifestations, including acute and chronic antiphospholipid-associated nephropathy (APLN). Clinical presentations of lupus nephritis and APLN are similar and a renal biopsy is necessary to differentiate between the conditions. Our aim with this study was to investigate the occurrence of histopathological findings consistent with APLN (hAPLN) in renal biopsies from SLE patients and to investigate associations with anti-phospholipid antibody specificities, clinical manifestations, HLA-DRB1 alleles, and long-term renal outcome.MethodConsecutive renal biopsies from 112 SLE patients with renal involvement were investigated and evaluated for findings of hAPLN; in all there were 236 renal biopsies. Data from biopsy reports and clinical information were collected. Autoantibodies against cardiolipin and β2-glycoprotein-1 were measured by enzyme-linked immunosorbent assay. A lupus anticoagulant test was determined with a modified Dilute Russel Viper Venom method. HLA genotyping was performed by sequence-specific primer PCR. Renal outcome was determined at study end.ResultsThe prevalence of hAPLN was 14.3% among SLE patients with renal involvement. Compared to patients with pure lupus nephritis, occurrence of hAPLN was associated with intima changes (odds ratio (OR) = 24; 95% confidence interval (CI), 3.0 to 189.8; P < 0.0001), hypertensive vascular changes (OR = 7.8; 95% CI, 1.6 to 39.4; P = 0.01), inflammatory infiltrates (OR = 6.5; 95% CI, 1.7 to 25.1; P = 0.007) and tubular atrophy (OR = 13.1; 95% CI, 1.7 to 103.6; P = 0.002). hAPLN was associated with the presence of cardiolipin antibodies (OR = 3.3; 95% CI, 1.0 to 10.8; P = 0.05) and triple anti-phospholipid antibody positivity (OR = 4.2; 95% CI, 1.3 to 13.7; P = 0.02). Patients with hAPLN were more hypertensive (OR = 3.8; 95% CI, 1.2 to 12.3; P = 0.03) and had higher levels of creatinine as compared to lupus nephritis patients (median 116 versus 75 μmol/L; P < 0.0001). We found significantly higher frequency of HLA-DRB1*13 (OR = 5.1; 95% CI, 1.7 to 15.4; P = 0.03) and development of end-stage renal disease (OR = 5.8; 95% CI, 1.7 to 19.7; P = 0.008) in hAPLN compared with lupus nephritis.ConclusionhAPLN is a severe and often unrecognized condition in SLE patients with renal involvement. We have demonstrated an increased risk for development of renal impairment and a genetic predisposition in hAPLN patients compared to lupus nephritis patients.

The relationship between mean platelet volume and thrombosis recurrence in patients diagnosed with antiphospholipid syndrome

Increased mean platelet volume (MPV) is associated with platelet reactivity and is a predictor of cardiovascular risk and unprovoked venous thromboembolism. The aim of our study was to evaluate MPV in patients with confirmed antiphospholipid antibody syndrome (APS) and to identify the correlation between the value of MPV and the recurrence of thrombosis. The studied group consists of 247 patients with a history of thrombosis and/or pregnancy loss (median age 38, range 18–66 years) classified as APS group (n = 70) or APS negative patients (n = 177) according to the updated Sapporo criteria. The control group consisted of 98 healthy subjects. MPV was significantly higher in the group of patients with clinically and laboratory confirmed APS (median 7.85, range 4.73–12.2 fl) in comparison with the controls. It was also higher than in APS negative patients (7.61, range 5.21–12.3 fl). APS patients with triple positivity for antiphospholipid antibodies with respect to Miyakis classification categories had higher MPV values than other APS patients (9.69 ± 1.85 vs. 7.29 ± 1.3 fl, p = 0.001). Recurrent thrombotic episodes were observed in 83 patients, but among the triple positive high-risk patients with APS in 80 % cases (p = 0.0046). In receiver operating characteristic curve analysis, the value of MPV level for thrombosis recurrence prediction in the APS group with sensitivity of 86 % and specificity of 82 % was 7.4 fl. In the multivariate logistic regression model, MPV above 7.4 fl (OR 3.65; 95 % CI 1.38–9.64, p = 0.009) significantly predicts thrombosis recurrence. Our results identify the value of MPV as a prognostic factor of thrombosis recurrence in patients with APS.

THU0296 Recurrence of Thrombotic Events in Young Patients with Primary Antiphospholipid Syndrome Related with Triple Positivity for Antiphospholipd Antibodies

BackgroundThrombotic events are formal clinical criteria for the diagnosis of Antiphospholipid Syndrome (APS). By now there are no evidences if there is an antibody profile or a specific risk factor...

Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome

To investigate the predictive value of serum C3 and C4 complement component levels in relation to pregnancy outcome in patients with antiphospholipid syndrome (APS). A prospective study of 47 pregnancies associated with APS was performed. Pregnancy outcome was analyzed in terms of: fetal loss, preterm delivery (≤34 gestational weeks), fetal intrauterine growth restriction (IUGR), birth weight <2500 g and preeclampsia. Week at delivery, neonatal birth weight and neonatal birth weight percentile were also investigated. Hypocomplementemia, positivity for anti-dsDNA and triple positivity for antiphospholipid antibodies (aPL) were related to pregnancy outcome. Forty-three pregnancies ended in live births with a fetal loss rate of 8.5%. Fetal death, preterm delivery and birth weight <2500 g were associated with hypocomplementemia (p = 0.019, p = 0.0002, p < 0.0001 respectively). Lower neonatal birth weight, lower neonatal birth weight percentile and lower week at delivery were associated with hypocomplementemia (p < 0.0001, p = 0.0003, p < 0.0001 respectively) and with triple aPL positivity (p = 0.008, p = 0.014, p = 0.03 respectively). A poor pregnancy outcome was confirmed among primary APS (PAPS) pregnancies with hypocomplementemia. Multivariate analysis confirmed that hypocomplementemia was an independent predictor of lower neonatal birth weight (p = 0.0001) and lower week at delivery (p = 0.002). Hypocomplementemia could be considered a novel prognostic factor for pregnancy outcome in APS patients.

Risk-based secondary prevention of obstetric antiphospholipid syndrome

Treatment of pregnant women with antiphospholipid syndrome (APS) should be set apart from that from thrombotic APS patients. Patients with a history of pregnancy morbidity but no vascular thrombosis are usually treated with a prophylactic dose of heparin plus low-dose aspirin; whereas, those with previous vascular thrombosis alone or associated with previous pregnancy morbidity, are commonly treated with a therapeutic dose of heparin generally combined with low-dose aspirin. However, in about 20% of pregnant APS women these regimens fail. In this context, we conducted a case-control study on a large multicentre cohort of conventionally treated pregnancies to verify whether specific laboratory profiles and/or clinical characteristics are predictive of unsuccessful pregnancy outcome during conventional treatments. Multivariate analysis showed that pregnancy failure during conventional therapies was independently associated with a history of both thrombosis and pregnancy morbidity, the presence of systemic lupus erythematosus (SLE) or other systemic autoimmune diseases and triple antiphospholipid antibody positivity. With the aim to discover the most effective and safe treatments in high-risk pregnant APS women a large-scale multicentre study focusing on the effect of treatments on pregnancy outcome in women with APS and further risk factors for pregnancy failure has been designed.