Case Report: Resetting the Humoral Immune Response by Targeting Plasma Cells With Daratumumab in Anti-Phospholipid Syndrome.

Introduction: Monoclonal antibodies (mAb) targeting plasma cells are malignant gammopathy designed and approved therapies. In recent years, these antibodies have also been increasingly introduced for non-malignant conditions such as autoimmune-mediated diseases. The Anti-Phospholipid Syndrome (APS) is an immune-mediated disorder in which autoantibodies against phospholipid associated proteins could elicit the activation of the coagulation cascade in specific situations. Therefore, the mainstream treatment for APS patients is the use of anticoagulant therapy. However, there are refractory patients who would benefit from targeting the antibodies rather than their effects. Rituximab, a B-cell depleting mAb, and intravenous immunoglobulins (IVIG) have been used in APS patients without showing a clear beneficial effect or a significant drop in anti-phospholipid antibody (aPL) levels. Clinical case: We present our first APS case treated with daratumumab, an anti-CD38 mAb, in a 21-year-old patient with APS who presented with recurrent venous thromboembolic events despite adequate anticoagulant therapy. She tested positive for lupus anticoagulant, anti-cardiolipin IgG, anti-beta-2-glycoprotein-I IgG and anti-phosphatidylserine/prothrombin IgG and IgM. She was administered one dose weekly of daratumumab for 4 weeks. The treatment showed an adequate safety profile and was well tolerated. The patient was discharged after undergoing a clinically significant improvement. After the therapy, her levels of positive aPL declined significantly and most continued to decrease during the next three months. The patient experienced a new thrombotic episode two years after the therapy associated with poor adherence to antithrombotic therapy. Conclusions: The treatment with daratumumab showed an adequate safety profile, was well tolerated and led to a significant clinical improvement. Levels of aPL lowered on therapy and the next three months and then rose again during follow-up. Further investigation is needed to better elucidate the role and optimal timing and doses of daratumumab in treatment of refractory APS.

Growth differentiation factor 15 (GDF-15) as potential cardiovascular risk biomarker in antiphospholipid syndrome.

OBJECTIVE: An interplay between thrombo-inflammatory and atherogenic mechanisms is recognized in cardiovascular disease (CVD) pathogenesis in APS. Herein, we examine associations of growth differentiation factor-15 (GDF-15), a pro-inflammatory cytokine identified as a potent CVD risk biomarker in the general population, with subclinical atherosclerosis in APS. METHODS: We measured plasma GDF-15 levels by an electrochemiluminescence immunoassay (cut-off 1200 pg/ml) and we examined carotid intima-media thickness (IMT) and the presence of carotid and femoral plaques using vascular ultrasound in 80 patients with APS (44 primary, 36 SLE/APS) and 40 healthy controls. We calculated the adjusted Global APS Score for cardiovascular disease (aGAPSSCVD), a revised adjusted Global APS Score (aGAPSS) for predicting CVD, including lupus anticoagulant, anticardiolipin and anti-beta2glycoprotein-I antibodies, and hypertension, dyslipidaemia, obesity, diabetes and smoking. RESULTS: GDF-15 levels were higher in APS patients vs controls, after adjusting for age and gender [absolute difference: 281 (95% CI: 141, 421) pg/ml, P < 0.001]. GDF-15 levels ≥1200 pg/ml were associated with higher mean IMT of the right and left carotid arteries [beta coefficient 0.068 (95% CI: 0.020, 0.116), P = 0.006] compared with GDF-15 levels <1200 pg/ml. GDF-15 was independently associated with mean IMT, after adjusting for gender and aGAPSSCVD [beta coefficient 0.059 (95% CI: 0.008, 0.110), P = 0.024], and additionally for statin (P = 0.025) and HCQ use (P = 0.011). GDF-15 levels ≥1200 pg/ml were associated with 2.4 times higher odds for atherosclerotic plaques (odds ratios = 2.438, 95% CI: 0.906, 6.556, P = 0.078), while this effect was reduced by including more covariates in the model. CONCLUSION: GDF-15 is independently associated with subclinical atherosclerosis in APS patients, suggesting its potential role in CVD risk stratification in APS.

Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome.

OBJECTIVE: Amyloid-beta1-40 (Aß40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein we tested the hypothesis that Aß40 is deregulated in APS, a systemic autoimmune disease characterized by a thrombo-inflammatory state. METHODS: Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 SLE/APS) and 80 age- and sex-matched controls. Plasma Aß40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aß40 performance to detect arterial thrombotic APS-related events. RESULTS: Higher Aß40 levels were significantly associated with the presence of APS [odds ratio (OR) 1.024 per 1 pg/ml (95% CI 1.007, 1.041)] after adjustment for cardiovascular risk factors (CVRFs), including smoking, arterial hypertension, dyslipidaemia and BMI, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased high-sensitivity CRP (hs-CRP) serum levels was the only independent determinant of Aß40 levels. Importantly, Aß40 levels above the optimal receiver operating characteristics (ROC)-derived cut-off value were independently associated with recurrent arterial events [OR 4.93 (95% CI 1.31, 18.51)] after adjustment for age, sex, CVRFs, hs-CRP and high anti-ß2 glycoprotein I IgG titres. Finally, by ROC curve analysis, Aß40 provided incremental additive value over the aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses. CONCLUSION: In APS, Aß40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aß40 in APS merits further investigation.

Cognitive dysfunction and serum levels of brain-derived neurotrophic factor (BDNF) in primary anti-phospholipid syndrome (PAPS).

OBJECTIVES: Cognitive dysfunction (CD) is a poorly understood non-stroke central neurological manifestation in anti-phospholipid syndrome (APS). Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in neural plasticity and could potentially be a biomarker of CD in primary APS (PAPS). The aim of the study is to assess CD in PAPS patients and to evaluate its association with clinical data, anti-phospholipid antibodies and serum BDNF levels. METHODS: This cross-sectional study compared 44 PAPS patients and 20 healthy controls matched for age, gender and education. PAPS patients and controls underwent a standardized cognitive examination. The demographic, clinical and laboratory characteristics of patients were recorded. Serum BDNF was measured by Enzyme Linked Immunosorbent. RESULTS: Fourteen (31.8%) of the 44 patients with PAPS had CD compared with only one (5%) healthy control (P =0.019). PAPS patients presented lower serum BDNF levels when compared with controls (P =0.007). Lower levels of BDNF were associated with CD in PAPS patients (P =0.032). In the univariate analysis, a positive association was found between CD and livedo reticularis, deep vein thrombosis, stroke, seizure, smoking as well as a negative association with Mini Mental State Examination and serum BDNF. According to multivariate analysis, the only independent predictor of CD in PAPS was stroke (OR 137.06; 95% CI: 4.73, 3974.32; P =0.004). CONCLUSIONS: CD is commonly reported in PAPS patients; however, its assessment lacks in standards and objective screening tests. The association between CD and low serum BDNF suggests that this neurotrophin can be a promising biomarker for PAPS cognitive impairment.

A 44-Year-Old Woman With Chest Pain and Dyspnea.

CASE PRESENTATION: A 44-year-old woman with a medical history of anti-phospholipid antibody syndrome complicated by recurrent pulmonary emboli with subsequent chronic hypoxic respiratory failure (3 L/min oxygen baseline) presented to the ED with 2 to 3 weeks of shortness of breath and pleuritic chest pain that radiated to the center of her back. These symptoms were accompanied by an increase in her oxygen requirement from 3 L/min to 6 L/min. She also reported nausea, vomiting, lightheadedness, and dizziness for the same period. The patient had two prior pulmonary emboli in the same year, which prompted a hypercoagulable workup, ultimately revealing a diagnosis of antiphospholipid antibody syndrome. The second pulmonary embolus occurred while the patient was on coumadin, though achieving a therapeutic international normalized ratio was challenging. At the recommendation of the Hematology Department, she was transitioned to systemic anticoagulation with low-molecular-weight heparin (LMWH) at a dose of 1.5 mg/kg twice daily, which was her regimen at the time of admission. The patient confirmed total compliance with her anticoagulation therapy, and she denied any recent travel or long periods of being sedentary. She was up to date on her age-appropriate cancer screening, without any evidence of active malignancy.

Two of a kind? Immunological and clinical risk factors differ between recurrent implantation failure and recurrent miscarriage.

Recurrent miscarriage (RM) and recurrent implantation failure (RIF) are unsolved challenges in reproductive medicine. Whether RIF patients share the same risk factors as RM patients is a matter of debate. Besides clinical factors, immune alterations are discussed in both conditions. The scope of this study was to compare the prevalence of clinical and immunological risk factors in a large cohort of RM and RIF patients. Between 11/2011 and 02/2019, 613 RM and 185 RIF patients were included. A screening for anatomical malformations, endocrine, autoimmune, prothrombotic and parental chromosomal disorders was performed. The immune status was assessed using flow cytometry analysis of peripheral lymphocyte subpopulations and uterine natural killer cells (uNK cells) using immunohistochemistry. RM patients showed a higher rate of intrauterine adhesions and elevated antinuclear antibodies ≥ 1:160 (p < 0.05). A higher prevalence of submucous fibroids and increased factor VIII levels were observed in RIF patients (p < 0.05). The prevalence of an antiphospholipid syndrome (APLS) was low and did not differ between the two groups. RIF patients had higher numbers of peripheral regulatory T-cells (p < 0.05). Significant more RIF patients were diagnosed with elevated uNK cells (p < 0.05). Differences in clinical and immunological risk factors of RM and RIF patients reflect different entities. Lower Tregs in RM and higher uNK cells in RIF patients might be related to the previous exposure of the immune system to fetal cells. The low prevalence of an APLS indicates a potential overestimation of this factor in the pathophysiology of RM and RIF.

Antiphospholipid antibodies in patients with dysglycaemia: A neglected cardiovascular risk factor?

BACKGROUND: Cardiovascular disease is a serious complication in patients with dysglycaemia, defined as either type 2 diabetes or impaired glucose tolerance. Research focusing on the identification of potential markers for atherothrombotic disease in these subjects is warranted. The antiphospholipid syndrome is a common acquired prothrombotic condition, defined by a combination of thrombotic events and/or obstetric morbidity and positivity of specific antiphospholipid antibodies. Available information on antiphospholipid antibodies in dysglycaemia is scarce. OBJECTIVE: This study investigates the association between antiphospholipid antibodies and dysglycaemia. PATIENTS/METHODS: The PAROKRANK (periodontitis and its relation to coronary artery disease) study included 805 patients, investigated 6-10 weeks after a first myocardial infarction, and 805 matched controls. Participants without known diabetes (91%) underwent an oral glucose tolerance test. Associations between antiphospholipid antibodies (anti-cardiolipin and anti-ß2 glycoprotein-I IgG, IgM and IgA) and dysglycaemia were analysed. RESULTS: In total, 137 (9%) subjects had previously known type 2 diabetes and 371 (23%) newly diagnosed dysglycaemia. Compared with the normoglycaemic participants, those with dysglycaemia had a higher proportion with first myocardial infarction (61% vs 45%, p < 0.0001) and were more often antiphospholipid antibody IgG positive (8% vs 5%; p = 0.013). HbA1c, fasting glucose and 2-h glucose were significantly associated to antiphospholipid antibody IgG. Odds ratios (ORs) were 1.04 (95% confidence interval [CI] 1.02-1.06), 1.14 (95% CI 1.00 - 1.27) and 1.12 (95% CI 1.04 - 1.21), respectively, after adjustments for age, gender and smoking. CONCLUSIONS: This study reports an association between antiphospholipid antibody IgG positivity and dysglycaemia. Further studies are needed to verify these findings and to investigate if antithrombotic therapy reduces vascular complications in antiphospholipid antibody positive subjects with dysglycaemia.

Primary antiphospholipid syndrome in a hemodialysis patient with recurrent thrombosis of arteriovenous fistulas / Síndrome antifosfolípide primária em paciente em hemodiálise com trombose recorrente de fístulas arteriovenosas

ABSTRACT Introduction: The antiphospholipid syndrome is a systemic autoimmune disease defined by recurrent vascular and/or obstetrical morbidity that occurs in patients with persistent antiphospholipid antibodies. Case presentation: A patient on hemodialysis with a primary antiphospholipid syndrome presented with recurrent vascular access thrombosis, obstetrical complications, and positive lupus anticoagulant. The patient had multiple arteriovenous fistulas that failed due to thrombosis. The obstetrical morbidity was defined by one miscarriage at the 7th week of gestation and a pregnancy complicated by pre-eclampsia with preterm delivery at the 28th week of gestation. A thorough thrombophilia screening confirmed the presence of antiphospholipid antibody. Lupus anticoagulant was present in plasma, measured on two occasions 12 weeks apart. Conclusion: Thrombophilias are inherited or acquired predispositions to vascular thrombosis and have been associated with thrombosis of the arteriovenous fistula. Patients on hemodialysis with recurrent vascular access thrombosis and presence of thrombophilia should be evaluated about the need for anticoagulant therapy with a vitamin K antagonist.

RESUMO Introdução: A síndrome antifosfolipídica é uma doença autoimune sistêmica definida por morbidade vascular e/ou obstétrica, recorrente, que acomete pacientes com anticorpos antifosfolípides persistentes. Apresentação do caso: Uma paciente em hemodiálise com síndrome antifosfolípide primária apresentou trombose recorrente do acesso vascular, complicações obstétricas e anticoagulante lúpico positivo. A paciente apresentava múltiplas fístulas arteriovenosas que falharam devido à trombose. A morbidade obstétrica foi definida por um aborto espontâneo na 7ª semana de gestação e uma gravidez complicada por pré-eclâmpsia com parto prematuro na 28ª semana de gestação. Um rastreamento completo de trombofilia confirmou a presença de anticorpo antifosfolípide. O anticoagulante lúpico estava presente no plasma, medido em duas ocasiões, com 12 semanas de intervalo. Conclusão: As trombofilias são predisposições hereditárias ou adquiridas para trombose vascular e têm sido associadas à trombose da fístula arteriovenosa. Pacientes em hemodiálise com trombose recorrente de acesso vascular e presença de trombofilia devem ser avaliados quanto à necessidade de terapia anticoagulante com um antagonista da vitamina K.

Primary antiphospholipid syndrome associated with anti-phospholipase A2 receptor antibody-positive membranous nephropathy.

BACKGROUND: The kidney is a major target in primary antiphospholipid syndrome. Several types of nephropathy have been reported, the most frequent being acute or chronic specific vascular nephropathies and membranous nephropathy. CASE PRESENTATION: A 59-year-old male presented in our unit with nephrotic syndrome. He had a history of primary antiphospholipid syndrome with lupus anticoagulant treated with vitamin K antagonist therapy. On admission, antiphospholipid (lupus anticoagulant) and anti-PLA2R antibodies were positive. Screening for secondary etiologies was negative. In the context of primary antiphospholipid syndrome treated with vitamin K antagonist therapy, we did not perform a biopsy and we treated the patient with angiotensin-converting-enzyme inhibitor. No remission was observed at 6 months with persistent anti-PLA2R antibodies while antiphospholipid antibody level became negative. Consequently, kidney biopsy was performed showing both membranous nephropathy with PLA2R in deposits on immunohistochemistry with IgG4 dominance and antiphospholipid syndrome chronic vascular nephropathy. Following that, treatment with rituximab was started with secondarily a decrease in serum PLA2R antibody levels and partial remission. CONCLUSION: We report the first association between primary antiphospholipid syndrome and membranous nephropathy with anti-PLA2R antibodies. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related membranous nephropathy. Consequently, it would be interesting to screen for anti-PLA2R antibodies for further cases of nephrotic syndrome in patients with primary antiphospholipid syndrome and to search antiphospholipid antibodies in all membranous nephropathies.

Antiphospholipid antibody-activated NETs exacerbate trophoblast and endothelial cell injury in obstetric antiphospholipid syndrome.

Despite the widespread use of antiplatelets and anticoagulants, women with antiphospholipid syndrome (APS) may face pregnancy complications associated with placental dysplasia. Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many autoimmune diseases, including vascular APS; however, their role in obstetric APS is unclear. Herein, we investigated the role of NETs by quantifying cell-free DNA and NET marker levels. Live-cell imaging was used to visualize NET formation, and MAPK signalling pathway proteins were analysed. Cell migration, invasion and tube formation assays were performed to observe the effects of NETs on trophoblasts and human umbilical vein endothelial cells (HUVECs). The concentrations of cell-free DNA and NETs in sera of pregnant patients with APS were elevated compared with that of healthy controls (HCs) matched to gestational week. APS neutrophils were predisposed to spontaneous NET release and IgG purified from the patients (APS-IgG) induced neutrophils from HCs to release NETs. Additionally, APS-IgG NET induction was abolished with inhibitors of reactive oxygen species, AKT, p38 MAPK and ERK1/2. Moreover, NETs were detrimental to trophoblasts and HUVECs. In summary, APS-IgG-induced NET formation deserves further investigation as a potential novel therapeutic target in obstetrical APS.

The importance of antiphospholipid syndrome testing in venous thromboembolism after varicose vein surgery.

Anticoagulation treatment after a venous thromboembolism event is usually managed on a case-by-case basis. The risk of thrombosis must be weighed against the risk of bleeding. Identifying patients who could benefit from anticoagulation therapy requires the thromboembolism event to be assessed with respect to its presentation and the severity of the triggering factors. A case report is employed to explain the important aspects of practical approaches to venous thromboembolism events after vein surgery. The Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS) study has prompted new considerations for anticoagulation management. Patients with antiphospholipid syndrome need to be identified early to lower the risk of thromboembolism also during anticoagulation treatment.

Inflammatory markers in thrombosis associated with primary antiphospholipid syndrome.

The role of inflammation in thrombotic complications of primary antiphospholipid syndrome (PAPS) is controversial. The aim of this study was to evaluate levels of inflammation and coagulation markers in patients with thrombotic PAPS (t-PAPS). Patients with t-PAPS and individuals with no history of thrombosis were enrolled. The association of t-PAPS with levels of tumor necrosis factor (TNF)-α, C-reactive protein (hs-CRP), interferon (IFN)-α, interleukins (IL)-6, -8, factor VIII (FVIII), von Willebrand factor (VWF) and tissue factor (TF) was evaluated by regression models. The levels of these markers were also compared between controls and subgroups of t-PAPS patients with triple positivity, recently diagnosed thrombosis, recurrent thrombosis and venous thrombosis. Patients with t-PAPS (n = 101) had a 8.6-fold increased levels of TNF-α, 90% increased levels of hs-CRP, 80% increased levels of IL-6, 30% increased levels of FVIIIAg, 50% increased levels of VWF and 66% increased levels of TF as compared to controls (n = 131), and the differences did not change after adjustments for sex, age and cardiovascular risk factors. Inflammatory markers were elevated in t-PAPS regardless of the aPL profile, number of previous thrombosis or time elapsed since diagnosis. TNF-α and IL-8 levels were higher in t-PAPS patients with venous thrombosis, in comparison with those with arterial thrombosis and controls. Patients with t-PAPS presented with increased levels of inflammatory and coagulation markers, which suggests that t-PAPS is associated not only with hypercoagulability but also with a persistent inflammatory state.

A 36-Year-Old Woman Presenting With Left Upper Quadrant Discomfort, Encephalopathy, and Respiratory Failure.

CASE PRESENTATION: A 36-year-old woman with a history of hypertension and alcoholism reported 2 days of left upper quadrant pain and jaundice. Within hours of admission, she became somnolent and hypoxic. The patient was then intubated. She had no history of drug abuse, cigarette smoking, liver disease, autoimmune disease, or pancreatitis. She had no home medications.

An in vitro model to mimic the thrombotic occlusion of small vessels in catastrophic antiphospholipid syndrome (CAPS).

Platelet activation and decrease in platelet count characterize the development of the most feared form of antiphospholipid syndrome (APS), i.e. catastrophic APS (CAPS). We aimed to assess if immuno-affinity purified anti-ß2-glycoprotein I (aß2GPI) antibodies enhance platelet activation inducing a significant flow obstruction in a platelet function analyzer (PFA). Affinity purified aß2GPI antibodies were obtained from 13 triple positive patients with a strong lupus anticoagulant (LA) and high titers of IgG anticardiolipin antibodies (aCL) and IgG aß2GPI. Platelet activation stimulated by adenosine diphosphate (ADP) in the presence or absence of aß2GPI was measured by the expression of P-selectin on platelet surface using flow cytometry. P-selectin expression remained close to baseline when normal whole blood was incubated with aß2GPI alone. When stimulated using aß2GPI combined with ADP, P-selectin expression (28.42 ± 5.15% vs. 20.98 ± 3.94%, p = 0.0076) was significantly higher than ADP alone. Closure time of normal whole blood passed through the PFA was significantly shorter using affinity purified aß2GPI than control IgG both in Col/ADP (160.1 ± 62.1 s vs. 218.6 ± 43.8 s; p = 0.021) and Col/EPI cartridges (149.5 ± 26.7 s vs. 186.9 ± 45.5 s; p = 0.030). Thus, platelet activation is enhanced by aß2GPI antibodies with a consequent premature closure in a PFA, possibly resembling that in microcirculation in patients with CAPS.

Hyperferritinaemia: An Iron Sword of Autoimmunity.

BACKGROUND: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. METHODS: Different electronic databases were searched in a non-systematic way to find out the literature of interest. RESULTS: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still's diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. CONCLUSION: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

Apoptosis in patients with primary antiphospholipid antibody syndrome.

AIM: Dysregulated apoptosis has been implicated in autoimmune diseases. In the present study, we investigated the apoptosis-related cytokines and apoptosis in patients with primary antiphospholipid syndrome (pAPS). METHOD: We prospectively recruited 12 pAPS patients, 17 antiphospholipid antibody (APA)-positive systemic lupus erythematosus (SLE) patients without APS manifestations (APA+ SLE), 13 SLE patients with secondary APS (APS+ SLE) and 10 healthy controls (HCs). Plasma levels of soluble apoptosis-inducing ligands and cytokines, and the expression levels of apoptosis-inducing ligands in peripheral blood mononuclear cells, were determined. In addition, blood lymphocytes/monocytes apoptosis were determined in six pAPS patients and six HCs, using flow cytometric analysis of caspase 3, 8 and 9 activities. RESULTS: There was a trend toward higher plasma levels of soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL), interleukin-10 (IL-10) and TNF-α in pAPS patients when compared with HCs. We also observed higher plasma levels of IL-10 and TNF α in APA+ SLE and APS+ SLE patients when compared with HCs. However, there was no significant difference in blood lymphocytes/monocytes apoptosis between pAPS patients and HCs. CONCLUSION: There was a trend toward elevated plasma levels of sTRAIL, IL-10 and TNF-α, but no evidence for dysregulated apoptosis in pAPS patients.

The Impact of Systemic Lupus Erythematosus on the Clinical Phenotype of Antiphospholipid Antibody-Positive Patients: Results From the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Clinical Database and Repository.

OBJECTIVE: Although systemic lupus erythematosus (SLE) is the most common autoimmune disease associated with antiphospholipid antibodies (aPL), limited data exist regarding the impact of SLE on the clinical phenotype of aPL-positive patients. The primary objective of this study was to compare the clinical, laboratory, and treatment characteristics of aPL-positive patients with SLE with those of aPL-positive patients without SLE. METHODS: A secure web-based data capture system was used to store patient demographic characteristics and aPL-related clinical and laboratory characteristics. Inclusion criteria included positive aPL according to the updated Sapporo classification criteria. Antiphospholipid antibody-positive patients fulfilling the American College of Rheumatology criteria for the classification of SLE ("aPL with SLE") and those with no other autoimmune diseases ("aPL only") were included in the analysis. RESULTS: Six hundred seventy-two aPL-positive patients were recruited from 24 international centers; 426 of these patients did not have other autoimmune disease, and 197 had SLE. The frequency of thrombocytopenia, hemolytic anemia, low complement levels, and IgA anti-ß2 -glycoprotein I (anti-ß2 GPI) antibodies was higher in the aPL-positive patients with SLE, whereas the frequency of cognitive dysfunction and IgG anti-ß2 GPI antibodies was higher in the aPL-only group. The frequency of arterial and venous thromboses (including recurrent) as well as pregnancy morbidity was similar in the 2 groups. The prevalence of cardiovascular disease risk factors at the time of entry into the registry entry did not differ between the 2 groups, with the exception of current smoking, which was more frequent in aPL-positive patients with SLE. CONCLUSION: Although the frequencies of thrombosis and pregnancy morbidity are similar in aPL-positive patients with and those without SLE, the diagnosis of SLE in patients with persistently positive aPL is associated with an increased frequency of thrombocytopenia, hemolytic anemia, low complement levels, and positive IgA anti-ß2 GPI antibodies.

Successful Endovascular Treatment for Aortic Thrombosis Due to Primary Antiphospholipid Syndrome: A Case Report and Literature Review.

A 60-year-old man with a history of Raynaud's phenomenon presented with bilateral intermittent claudication and an ulcer on his right toe. The ankle-brachial index of the right and left legs was 0.77 and 0.75, respectively. Laboratory data showed prolongation of the activated partial thromboplastin time and a positive result on the lupus anticoagulant test. Computed tomography angiography revealed isolated infrarenal aortic stenosis with irregular surface and noncalcified plaques. Intravascular ultrasonography examination demonstrated a noncalcified, irregular, and mobile plaque, suggestive of abdominal aortic thrombosis. In addition to anticoagulant and dual antiplatelet therapy, endovascular treatment was performed. A total of three 40-mm-long balloon-expandable stents were successfully implanted on a 15-mm balloon. The final angiography showed good results except for minimal plaque shifting in the terminal aorta. Three months later, the ulcer resolved and a final diagnosis of primary antiphospholipid syndrome (APS) was made. Clinicians should recognize that APS can affect the abdominal aorta, leading to aortic thrombosis. Endovascular treatment may be the one good treatment option for this rare condition.