Triple-positive Antiphospholipid Antibodies Research Articles

H3K4me3-Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in β2GPI/Anti-β2GPI-Treated Monocytes.

Antiphospholipid syndrome (APS) is characterized by thrombus formation, poor pregnancy outcomes, and a proinflammatory response. H3K4me3-related monocytes activation are key regulators of APS pathogenesis. Therefore, H3K4me3 CUT&Tag and ATAC-seq are performed to examine the epigenetic profiles. The results indicate that the H3K4me3 signal and chromatin accessibility at the FOXJ2 promoter are enhanced in an in vitro monocyte model by stimulation with β2GPI/anti-β2GPI, which mimics APS, and decreases after OICR-9429 administration. Furthermore, FOXJ2 is highly expressed in patients with primary APS (PAPS) and is the highest in patients with triple-positive antiphospholipid antibodies (aPLs). Mechanistically, FOXJ2 directly binds to the SLAMF8 promoter and activates SLAMF8 transcription. SLAMF8 further interacts with TREM1 to stimulate TLR4/NF-κB signaling and prohibit autophagy. Knockdown of FOXJ2, SLAMF8, or TREM1 blocks TLR4/NF-κB and provokes autophagy, subsequently inhibiting the release of inflammatory and thrombotic indicators. A mouse model of vascular APS is established via β2GPI intraperitoneal injection, and the results suggest that OICR-9429 administration attenuates the inflammatory response and thrombus formation by inactivating FOXJ2/SLAMF8/TREM1 signaling. These findings highlight the overexpression of H3K4me3-mediated FOXJ2 in APS, which consequently accelerates APS pathogenesis by triggering inflammation and thrombosis via boosting the SLAMF8/TREM1 axis. Therefore, OICR-9429 is a promising candidate drug for APS therapy.

Risk factors of first thrombosis in obstetric antiphospholipid syndrome

ObjectiveThere is limited evidence on long-term thrombosis risk in patients with obstetric antiphospholipid syndrome (OAPS). This study aimed to investigate the clinical features and risk factors associated with the first...

Rare Case of Secondary Evans Syndrome in Setting of Triple Positive Anti-Phospholipid Antibodies

Rare Case of Secondary Evans Syndrome in Setting of Triple Positive Anti-Phospholipid Antibodies

Successful treatment of lupus anticoagulant hypoprothrombinemia syndrome with rituximab

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder secondary to development of antibodies against prothrombin protein, in the presence of antiphospholipid antibodies. We describe the case of a 13-year-old girl who presented with severe menorrhagia and symptomatic anemia. Labs indicated anemia, thrombocytopenia, elevated PT and aPTT, high-titer inhibitor on mixing studies, positive ANA and anti-dsDNA antibodies, along with a triple-positive antiphospholipid antibody panel. Given additional systemic manifestations, systemic lupus erythematosus was diagnosed. High dose steroids and hydroxychloroquine subsequently started. Her clinical course was complicated by femoral deep venous thrombosis and post renal biopsy retroperitoneal hematoma. Further workup revealed low prothrombin level and the diagnosis of lupus anticoagulant hypoprothrombinemia syndrome. In view of suboptimal response to initial immunosuppressive therapy, rituximab was added to her regimen, leading to an improvement in clinical symptoms and resolution of hypoprothrombinemia. She remains recurrence free 5 years from the event.

A Case Report on Antiphospholipid Syndrome

Antiphospholipid syndrome is a systemic autoimmune disease characterized by the presence of antiphospholipid antibodies in association with thrombosis and/or obstetric complications. APS is also be presented with multiple organ involvement. We recently encountered a case of primary phospholipid syndrome in a young adult with newly diagnosed pulmonary embolism, immune thrombocytopenia and deep vein thrombosis of left leg. The diagnosis of APS was initially suspected with his prolonged APTT and elevated D-Dimmer values and later confirmed by triple positive antiphospholipid antibody profile and multiple organ involvement Keywords: Antiphospholipid syndrome, Thrombosis, Autoimmune disease.

Efficacy and Safety of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Meta-Analysis.

Due to a high risk of recurrent thromboembolism in patients with antiphospholipid syndrome (APS), long-term anticoagulation is recommended. For decades, vitamin K antagonists (VKAs) have been the gold standard for thromboprophylaxis in these patients. Due to the widespread use of direct oral anticoagulants (DOACs) in various thromboembolic conditions and their potential advantages compared to VKAs, several studies have been conducted to evaluate their safety and efficacy in APS.We performed a literature search using PubMed, Embase, and Cochrane databases for studies comparing DOACs to VKAs in patients with APS. Relative risk (RR) and the corresponding 95% confidence intervals (95% CI) were estimated for recurrent thromboembolic events, bleeding, and mortality.A total of 1437 patients pooled from 12 studies were analyzed. The risk of recurrent thrombosis, especially arterial thrombosis, doubled with DOACs compared to VKAs (RR 2.61, 95% CI 1.44-4.71; p=0.001). The risk further increased in patients with a triple-positive antiphospholipid antibody profile (RR 4.50, 95% CI 1.91-10.63; p=0.0006) and with the use of rivaroxaban (RR 1.95, 95% CI 1.10-3.45; p=0.02). The risk of major bleeding and mortality were not significantly different between the two arms. A trend favoring DOACs compared to VKAs was observed for all bleeding events. This meta-analysis comes in agreement with previous studies and supports the use of VKAs in APS. Our study revealed that VKAs remain the gold standard for the management of APS, especially triple-positive APS. DOACs, particularly rivaroxaban, are not as effective in preventing recurrent thromboembolism in high-risk APS patients. Further studies are needed to evaluate the role of DOACs apart from rivaroxaban with a focus on their efficacy in the management of isolated or double-positive APS.

Acquired and Inherited Thrombophilia Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension: Value of Testing in an Academic Health Center

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is classed as group 4 in the present classification of pulmonary hypertension. The pathophysiology of CTEPH is complex, mainly is a consequence of prior acute pulmonary embolism with failure of thrombi to resolve and the recent recognition of added small vessel changes which impacts long-term outcomes even after surgical management. The role of thrombophilia testing in this condition has been debated. Hence, we here analyzed the utility of thrombophilia testing in CTEPH from a center in a developing country.MethodsThis is a single institution (Narayana Health City, Bangalore); retrospective study including patients ≥ 18 years of age who underwent thrombophilia workup in a diagnosis of CTEPH from January 2019 till July 2021. Tests done to evaluate thrombophilia included factor V Leiden; prothrombin F20210A mutation; MTHFR gene mutation; Protein C, S, and antithrombin deficiency; lupus anticoagulant, anti-beta2 glycoprotein I (IgM and IgG) and anticardiolipin antibody (IgM and IgG); hyperhomocysteinemia and anti-nuclear antibody testing (ANA-IF). The study was approved by the ethics committee of the institute and was carried out in accordance with the principles of the declaration of Helsinki.Results and discussionThe study included 56 patients with a median age of 37 years (range 23-50), and 36 (64%) were males. Patients with recurrent venous thrombosis included 37 (66%), with the majority having thrombosis at 2 sites (53%; 22 patients with associated deep vein thrombosis). A family history of thrombosis was present in 4 patients. The majority of patients received vitamin K antagonists (76%), with the rest receiving direct oral anticoagulants (DOAC).Among the tests sent for acquired thrombophilia, ANA-IF and antiphospholipid antibody (APLA) were most frequently evaluated (94%). ANA-IF and APLA tests were positive in 5.6% and 30.1%, respectively. Among the APLA tests, Anti-beta2 glycoprotein I (IgM or IgG) was the most commonly detected antibody (13/46), followed by anticardiolipin antibody (IgG or IgM) (9/43) and lupus anticoagulant (7/40). Double and triple positive APLA were present in 3 and 4 patients, respectively. Homocysteine levels were high in 93.7% though only 16 patients were tested in this cohort.Among the tests for inherited thrombophilia, genetic tests (factor V Leiden, prothrombin F20210A mutation, and MTHFR gene mutation) were tested in only ~50%. Twenty-three percent were positive for heterozygous MTHFR followed by MTHFR compound heterozygous (10%) and heterozygous factor V Leiden heterozygous (10%). Antithrombin III, protein C, and S were tested in ~30% of patients. Antithrombin III was low in only 1 patient, with protein C and S assays being normal in all the patients.The cost analysis was calculated, showed a median of $364 (₹ 27,055) was spent per person on thrombophilia workup. The median cost incurred per patient for inherited thrombophilia workup was $232 (₹ 17,300) and for acquired thrombophilia was $132 (₹ 9814), respectively.ConclusionThis single-institution study on thrombophilia workup in CTEPH patients reveals that APLA was the most commonly performed test with high positivity rates of 30.1%. Among the inherited thrombophilia, the positivity rate of MTHFR mutation was highest (33.3%), with other tests having a low positivity rate (0-10%). Hence, we would recommend APLA testing in all patients with CTEPH considering its high positivity and clinical utility. Testing for other thrombophilias should be pursued judiciously especially in economically restrictive settings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

O25 Catastrophic antiphospholipid crisis triggered by anticoagulant switch

O25 Catastrophic antiphospholipid crisis triggered by anticoagulant switch

Therapeutic Plasma Exchange Improved Pregnancy Outcomes in a Patient with Triple Positive Anti-Phospholipid Antibody Syndrome

Therapeutic Plasma Exchange Improved Pregnancy Outcomes in a Patient with Triple Positive Anti-Phospholipid Antibody Syndrome

Direct oral anticoagulant use in special populations.

The pivotal phase III trials demonstrating efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF) excluded patients with important and common comorbidities, including obesity, advanced chronic kidney disease, cirrhosis, cancer and antiphospholipid antibody syndrome. Despite the lack of large prospective randomized control trials in these patient populations, the use of DOACs has led to a wealth of efficacy and safety data within these groups. Retrospective studies, meta-analyses, national databases and pharmacokinetic data have shed light on the efficacy and safety of DOACs in these patient populations. Although DOACs should be avoided in those with high-risk triple positive antiphospholipid antibody syndrome, advanced cirrhosis, advanced kidney disease and intact gastrointestinal cancers, and used with caution in genitourinary cancers, their use extends beyond the inclusion criteria of the initial randomized control trials. DOACs have revolutionized anticoagulant management and have become the cornerstone for VTE treatment and stroke prevention in NVAF. The decision to use DOACs must be individualized. Patient preference, underlying comorbidities and informed consent must always be considered when selecting the most appropriate anticoagulant.

P030 Antiphospholipid syndrome and giant cell arteritis: a coincidence or connection?

Abstract Background/Aims Antiphospholipid syndrome (APS) is a multisystem autoimmune disorder, which can be primary or associated with other conditions including systemic lupus erythematosus. Several studies have reported antiphospholipid antibodies, in patients with different vasculitides but little is known about the occurrence of APS and giant cell arteritis (GCA). We report a case of a patient diagnosed with concomitant extracranial GCA and APS. Methods A 74-year-old lady presented to the Emergency department following a fall at home. On further questioning, she reported a rapid history of weight loss (4kg in the previous 4 weeks) but no classical features of giant cell arteritis. Her temporal arteries were pulsatile bilaterally, not tender or thickened. Cranial nerve examination including fundoscopy was normal. Her gait was apraxic, with short stride length and veering to the right with a narrow base. The rest of the examination was unremarkable. Results Laboratory investigations showed an elevated CRP 98mg/L with a normal ESR 23mm/h, ferritin 380 ng/ml, negative ANCA and ANA, with an unremarkable myeloma screen. Microbiology investigations demonstrated negative serial blood cultures, hepatitis screen, and quantiferon. She subsequently underwent intracranial imaging [CT and MRI brain with Gadolinium] which did not demonstrate acute pathology. A PET CT confirmed features in keeping with a large vessel vasculitis without aneurysmal formation. She was treated with pulsed IV methylprednisolone 500mg for 3 consecutive days and started on 60mg oral prednisolone daily. Two days after starting this treatment she developed acute onset double vision: ophthalmologic examination revealed new onset right internuclear ophthalmolplegia (INO). A subsequent CT head angiogram showed non critical stenoses in aorta at origins of great vessels, left vertebral artery, and carotids. Interval MRI brain showed a new infarct in pons corresponding with her INO. Bloods revealed triple positive anti-phospholipid antibodies - [IgG anticardiolipin antibody 102 GPL (0-13), anti-β2 glycoprotein I antibodies 59.8 U/ml (0-18), Lupus anticoagulant detected]. She was commenced on warfarin [target INR 2.5] and aspirin. Due to mental health history and large vessel manifestations, she was started on IV Tocilizumab 8mg/kg and her prednisolone dose was reduced to 40mg when her CRP normalised. Following hospitalisation, she had persistent visual disturbance with ongoing poor spatial co-ordination. Although she remained ataxic, her functional mobility improved. She was transferred to a local stroke unit and was discharged home. Conclusion In summary, this is a case of GCA and APS, treated with prednisolone, aspirin, warfarin and tocilizumab. There is increasing evidence describing the presence of antiphospholipid antibodies in patients with vasculitis. However, the role of these antibodies in GCA and the clinical significance remains unclear. This case reports highlights the need for physicians to consider APS in patients who have a history of GCA and subsequently develop arterial or venous embolic events. Disclosure L. Sammut: None. E. Htut: None.

A CASE OF PHLEGMASIA CERULEA DOLENS AND MAY-THURNER SYNDROME IN A YOUNG MALE WITH TRIPLE-POSITIVE ANTIPHOSPHOLIPID ANTIBODY SYNDROME

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Phlegmasia cerulea dolens (PCD) is an uncommon form of deep vein thrombosis (DVT) typically presenting with acute limb swelling, pain, and cyanosis. Diagnosis of PCD should be made promptly as these patients may develop limb-threatening complications such as gangrene and compartment syndrome. We describe a young male presenting with his first episode of provoked venous thromboembolism (VTE) as PCD complicated with May-Thurner syndrome (MTS) and Antiphospholipid antibody syndrome (APS). CASE PRESENTATION: A 37-year-old obese male with type 2 diabetes, hypertension, and hyperlipidemia was directly admitted to the medicine floor with extensive left lower extremity DVT (including ileofemoral vein thrombosis) found on outpatient duplex ultrasonography. At initial hospitalization, he was tachycardic but without respiratory distress or hemodynamic instability. His left lower extremity was tender and edematous with cyanosis. Diagnosis of PCD was made and patient was treated with subcutaneous enoxaparin. He received catheter-directed thrombolysis for PCD with alteplase and heparin infusion. During left leg venogram, he was discovered to have MTS, and subsequently underwent stent placement of left common iliac vein, external iliac vein, and common femoral vein. After stent placement, patient received bridging to warfarin with enoxaparin and was discharged home two days later. Patient’s family history was significant for Systemic Lupus Erythematosus. During hospitalization, his antibody testing revealed positivity for anti-cardiolipin, anti-beta-2 glycoprotein antibodies in addition to positive functional lupus anticoagulant assay. Positivity confirmed with repeat testing of anti-cardiolipin antibodies and lupus anticoagulant assay at 15 weeks after hospitalization - confirming the diagnosis of triple-positive APS. DISCUSSION: Treatment of PCD is anticoagulation therapy with adjunctive catheter-directed thrombolysis. Outcomes comparing additional catheter-directed thrombolysis versus anticoagulation alone have shown that combination treatment reduces the incidence of post-thrombotic syndrome in patients with acute iliofemoral DVT. Recognition of DVT associated with MTS is important as treatment includes stent placement to maintain venous outflow. Recognition of triple-positive APS is an indication for extended anticoagulation as this portends a high risk of recurrent VTE. Patient was discharged with warfarin therapy because the use of direct oral anticoagulation in patients with APS remains controversial. Recent studies showed increased risk of recurrent thrombosis, particularly in patients with APS who are triple-positive. CONCLUSIONS: We reported a case, 37 year old male with phlegmasia cerulea dolens and May-Thurner syndrome resulting from triple-positive antiphospholipid antibody syndrome. Reference #1: Casey ET, Murad MH, Zumaeta-garcia M, et al. Treatment of acute iliofemoral deep vein thrombosis. J Vasc Surg. 2012;55(5):1463-73 Reference #2: Haig Y, Enden T, Grøtta O, et al. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016;3(2):e64-71 Reference #3: Dufrost V, Risse J, Reshetnyak T, et al. Increased risk of thrombosis in antiphospholipid syndrome patients treated with direct oral anticoagulants. Results from an international patient-level data meta-analysis. Autoimmun Rev. 2018;17(10):1011-1021 DISCLOSURES: No relevant relationships by Waqas Adeel, source=Web Response No relevant relationships by Robert Decker, source=Admin input No relevant relationships by Shuisen Li, source=Web Response No relevant relationships by Preysi Patel, source=Web Response No relevant relationships by Chun Siu, source=Web Response

Incidence, Natural History and Outcomes of Transient and Persistent Antiphospholipid Antibodies in Children and Young Adults with Provoked Venous Thromboembolism: Analysis of the Kids-DOTT Trial

Background: Antiphospholipid syndrome (APS) is characterized by the development of thromboembolic events in the setting of persistent antiphospholipid antibodies (APA). While several studies have investigated the clinical characteristics and venous thromboembolic (VTE) outcomes of pediatric patients with a diagnosis of APS, there is a scarcity of published data describing the incidence, natural history and VTE outcomes of children who present with positive APA at the time of an acute VTE episode. Objective: To describe the incidence, natural history and outcomes of transient and persistent APA in patients ≤21 years old with a first episode of provoked VTE. Methods: Patients with positive APA at the time of enrollment in an ongoing NHLBI-sponsored multicenter, parallel-cohort randomized controlled trial (RCT) on duration of anticoagulation therapy in provoked VTE (the Kids-DOTT Trial; NCT00687882) were included in this analysis. APA testing was obtained at the time of enrollment in all patients, and at 6 weeks post-VTE diagnosis in those with an initial positive APA result. Subsequent follow-up testing in patients whose APA persisted at 6 weeks post-VTE was performed at the discretion of the enrolling site's treating hematologist. Patients with persistent APA at 6 weeks were treated in a non-randomized parallel-cohort of the trial in which patients received at least a 3-month therapeutic course of anticoagulation. Those without persistent APA at 6 weeks were retained in the RCT and randomized to shortened-duration (no further therapy) versus conventional duration (total duration = 3 months) of therapy. Measured APA included lupus anticoagulant-sensitive activated partial thromboplastin time (LAS-aPTT), dilute Russell viper venom time (DRVVT), hexagonal phase phospholipid assay (STACLOT LA), anti-cardiolipin (ACL) IgM, and anti-beta-2-glycoprotein-1 (aß2GPI) IgG and IgM. Data were prospectively collected. Descriptive statistics were used to summarize data on demographic characteristics, VTE presentation, and outcomes of interest (persistent thrombus occlusion at 6 weeks post-VTE, post-thrombotic syndrome [PTS], recurrent VTE and clinically-relevant bleeding [CRB]). The blind was maintained in the Kids-DOTT trial throughout data transfer and analysis. Results: APA testing was performed in 476 patients at the time of enrollment. Twenty-one percent of patients (n=100) had at least one positive APA and were included in the present analysis. Demographics, VTE characteristics, and laboratory findings at enrollment are summarized in Table 1. Median age was 9.6 years (range 0.05-19). The most common thrombosis site was the lower extremity (43%). Presence of a central venous catheter was the provoking factor in 44% of cases. LA was the most common APA detected at the time of enrollment (36%, 35% and 13% of patients by STACLOT, DRVVT and LAS-aPTT, respectively). Twenty-four percent of patients had a persistent APA at 6 weeks post-VTE (Figure 1). Of these, 16 (66.7%) had repeat APA testing at least 12 weeks from first positive APA. Persistent APA at ≥12 weeks (i.e., APS) was determined in 12 of the 16 patients. Most of these children with APS had a single positive APA (aß2GPI IgG/IgM, n=4, LA, n=4, ACL IgM, n=2) while only 1 patient had triple-positive APA (Table 2). Rates of recurrent VTE, complete venous occlusion at 6 weeks post-VTE, development of PTS, and CRB were higher in APS patients as compared to those without APS (Table 3). Conclusions: This Kids-DOTT analysis reports for the first time that positive APA are found in nearly one quarter of children and young adults with provoked VTE at the time of the acute VTE episode, and that approximately 75% of these are transient (negative at 6 weeks post-VTE diagnosis). Patients with provoked VTE who have APS tended to have increased risk of adverse VTE outcomes when compared to those without APS; however, the size of these subgroups does not permit a definitively-powered comparison in outcomes. The putative role of persistently positive APAs as a prognostic factor for adverse VTE outcomes should be formally tested upon completion of the Kids-DOTT trial. Disclosures Tarango: Shire: Membership on an entity's Board of Directors or advisory committees; Bayer: Other: Study steering committee. Goldenberg:NIH: Other: research support and salary support.

Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome.

Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies have begun to be considered potentional biomarkers for antiphospholipid syndrome (APS). This cohort study investigate the role of aPS/PT antibodies as a risk factor for severe APS by evaluating the association between those antibodies and clinical/laboratory profiles of APS. Plasma/serum samples from 197 APS patients, 100 healthy subjects and 106 patients with autoimmune diseases were collected. IgG/IgM aPS/PT antibodies were assayed using commercial ELISA kit. Prevalences of IgG and IgM aPS/PT (p<0.0001 and p=0.0009, respectively) and their titres (p<0.0001 and p=0.0002, respectively) were significantly higher in thrombosis/pregnancy group with respect to pregnancy morbidity alone. Prevalences of IgG and IgM aPS/PT (p<0.0001 and p=0.0004, respectively) and their mean levels (p=0.0001 for both) were significantly higher in the prematurity linked to life-threatening obstetric complications group with respect to miscarriage group. There was a significant relationship between IgG and IgM aPS/PT (p=0.001 and p=0.0002) and their mean levels were higher (p=0.0004 and p=0.0002, respectively) in the thrombotic microangiopathy group, considered a milestone manifestation of catastrophic APS. The relationship between IgG and IgM aPS/PT was significant and mean levels were higher in triple positive antiphospholipid antibody patients than in double and single positivity ones (p<0.0001 for all). APS/PT antibodies were associated to severe thrombosis, severe pregnancy complications inducing prematurity, and vascular microangiopathy, all generally associated to high risk APS forms requiring strong therapy.

Antiphospholipid syndrome: analysis of dilute Russell's viper venom time titer.

To evaluate the characteristic features of the dilute Russell's viper venom time (DRVVT) titer in the antiphospholipid syndrome (APS). The medical record of 3660 consecutive patients with DRVVT orders between 2006 and 2015 were examined for criteria satisfying the diagnosis of APS. DRVVT titer was studied as a function of titer distribution, titer stability, and clinicopathologic features. Twenty-six patients were diagnosed with APS based on a persistently positive DRVVT and a history of arterial or venous thrombosis. DRVVT titer was mostly of low magnitude (65-77% of patients), was of similar value between initial and repeat testing (mean DRVVT titer 1.40 vs. 1.38; P = 0.858; mean time interval 216 days), and was positively associated with anticardiolipin antibodies (IgG and IgM) and antibeta-2-glycoprotein I antibodies (IgG and IgM) (P < 0.020). Low titer and moderate/high titer DRVVT were associated with a triple positive antiphospholipid antibody profile in 0 and 62% of patients, respectively (P < 0.020). DRVVT titer in APS was predominantly low in magnitude, stable over time, and associated with specific antiphospholipid antibody profiles.

Antibodies Directed Against the Domain 1 of Beta2-Glicoprotein 1 May be Associated with Secondary Antiphospholipid Syndrome

Background: The diagnosis of antiphospholipid syndrome (APS) is based on the persistent positivity of lupus anticoagulant (LA), IgM or IgG anticardiolipin (aCL) or IgG anti-β2 glicoprotein 1 (aβ2GP1) antibodies in patients plasma. Particularly, the role of antibodies directed against the domain 1 of β2GP1 (aβ2GP1-D1) has been described as relevant for the mechanism of immunopathogenesis in APS. However, the role of the aβ2GP1-D1 antibodies in clinical diagnosis and management of APS has not been established.Aim: The aim of this study was to evaluated the association of the presence of aβ2GP1-D1 antibodies with the clinical course of patients with thrombotic APS.Patients and methods: Patientspreviously diagnosed with thrombotic APS were consecutively selected for the study, from December 2013 to July 2014, in the Hemostasis Clinic of the Hematology and Hemotherapy Center of the University of Campinas. Demographic features and clinical conditions were recorded at the inclusion and during the follow-up. The clinical parameters analyzed were APS etiology (primary versus secondary to systemic autoimmune diseases), vascular bed of the thrombosis, history of multiple thrombosis, concomitant obstetrical morbidity, the presence of antinuclear antibodies (ANA) and the profile of the antiphospholipid antibodies. Anti-β2GP1-D1 antibodies were determined in patients plasma by chemiluminescence (BioFlash/AcuStar®, Barcelona, ES). Exact Fisher test and logistic regression were performed for statistical analysis. P < 0.05 were considered statistical significant.Results: Eight-five patients were included in the study, all patients presented venous or arterial thrombosis. The antibodies distribution among patients was: 80% LA positive, 50% aCL positive, 54% aβ2GP1 positive and 26% triple positive. Twenty-one patients (25%) tested positive for aβ2GP1-D1, 94% of them had positive aβ2GP1 antibody, previously detected at diagnosis. The presence of aβ2GP1-D1 was not associated with age or gender. Detected clinical conditions related to APS severity, such as thrombosis recurrence, concomitant obstetrical and vascular morbidity and triple positive antiphospholipid antibodies were evaluated. The positivity for aβ2GPI-DI antibodies was not associated with thrombosis recurrence (OR=1.0, 95%CI=0.37-2.71,P=1.0), concomitant obstetrical and vascular morbidity (OR=1.5, 95%CI=0.33-7.34, P=0.58), or triple positive antibodies (OR=2.79 , 95%CI=0.76 - 8.84, P=0.13). Anti-β2GP1-D1 antibodies were associated with the diagnosis of systemic autoimmune disease, in particular with lupus, (OR= 3.49 , 95%CI=1.25-9.76, P=0.01) and with positive ANA test (OR= 3.3, 95%CI=1.08-10.1, P=0.03).Conclusion: In this study, aβ2GPI-DI antibody was detected mainly in patients who had already tested positive for aβ2GP1 antibody, so it is possible that aβ2GP1-D1 assay may not provide additional sensibility to the diagnosis of APS. However, our results also suggested that the presence of aβ2GP1-D1 antibody might be associated to the diagnosis of secondary APS. The diagnosis of primary APS is based on the exclusion of systemic autoimmune diseases and there are no current laboratory parameters that discriminate between primary and secondary APS. Besides the laboratory criteria for lupus diagnosis, there may be overlapping of the antibodies and hematological features between APS and lupus. Furthermore, after the diagnosis of primary APS, it may take long time of follow-up to detect the underlying autoimmune disease. Therefore, if our findings are confirmed, aβ2GP1-D1 assays may play a role as a laboratory tool for the differential diagnosis between primary and secondary APS. DisclosuresNo relevant conflicts of interest to declare.

Triple positive antiphospholipid antibody profile in outpatients with tests for lupus anticoagulants.

A triple positive antiphospholipid (aPL) antibody profile [two positive serum IgG aPL antibodies along with one positive functional plasma lupus anticoagulant (LAC) test result] is associated with an increased risk for thrombosis, whereas patients with single positive test results may have little to no increased risk. The frequency of triple positivity in outpatients with various combinations of LAC test results is unclear. We extracted from our database all LAC test results [dilute Russell viper venom times (dRVVT) and silica clotting times (SCT)] that had concomitant serum IgG aPL testing [both serum anti β2-glycoprotein I (anti-β2GPI) and anti-cardiolipin (aCL) antibodies]. There were 3195 patients without a prolonged prothrombin time. Double antibody positivity was found in 1% (31/2955) of those with normal functional LAC test results, in 16.0% (31/81) of those with a positive dRVVT, in 12.7% (10/79) of those with a positive SCT, and in 56.3% (45/80) of those with both tests positive (p<0.001). A triple positive aPL antibody profile was found in 28.3% (68/240) of those with at least one positive LAC test result. We conclude that 28% of patients with elevated LAC tests have a triple positive aPL antibody profile and patients with two positive LAC tests have a higher prevalence of a triple positive profile than do those with one positive LAC test result.