Positive aCL Research Articles

Thrombotic antiphospholipid syndrome: Recurrent thromboses

Thrombotic antiphospholipid syndrome (APS) is a condition affecting young people in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL).The aim of this study was the evaluation of the incidence of recurrent thrombosis and its risk factors in antiphospholipid syndrome.Material and methods. The retrospective study included 98 patients with aPL who were followed up at the institute from 2014 to 2023, of whom 66 (67%) were women and 32 (33%) were men. Of the 98 patients with aPL, 48 (49%) had a diagnosis of systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL), including antibodies to cardiolipin (IgG/IgM aCL), antibodies to ß2-glycoprotein 1 (IgG/IgM aß2GP1), antibodies to ß2-glycoprotein IgG against domain 1 (IgG aß2GP1-D1), antibodies to phosphatidylserine/prothrombin complex (IgG/ IgM aPS/PT) and other thrombotic risk factors. aPL was assessed by enzyme-linked immunosorbent assay (ELISA) and chemoluminescence assay (CHLA).Results. Thrombosis recurrence was reported in 62 (63%) of 98 patients, and 36 (35%) did not. The main cause of recurrent thrombosis was treatment with direct oral anticoagulants (DOACs). 24 (38.7%) of 62 patients with recurrent thrombosis were treated with DOACs, the duration of which ranged from 6 to 24 months. The next most common cause of recurrent thrombosis was the lack of continuous anticoagulant therapy in 20 (32.5%) of the patients. In 17 (27.4%) of the patients, the recurrence occurred while they were still taking warfarin. In 10 (41.7%) of the 24 patients, the recurrent thrombosis was arterial in origin. This was associated with recurrent cerebral circulation problems. The level of positivity did not matter, but all had triple IgG aPL positivity. 5 had lupus anticoagulant (LA) at the onset of the disease before anticoagulant use. IgG aPS/PT was most important in association with recurring thrombosis in the ELISA: 45 (72.6%) of 62 patients with recurring thrombosis were positive for IgG aPS/PT, compared with 19 (52.8%) of 36 patients without recurring thrombosis. The detection of all aPL was more frequent in CHMA than in ELISA. However, the definition of aPL in ELISA is recommended according to the latest classification criteria. Triple IgG positivity for aCL of IgG aß2GP1, IgG aß2GP1-D1 and CHMA remained a risk factor for recurrent thrombosis and increased the risk of recurrence more than threefold. Obesity was a risk factor for recurrent thrombosis, with a 5-fold increased risk of recurrent thrombosis in obese compared to non-obese patients (p=0.01).Conclusions. Recurrent thrombosis in APS is largely associated with IgG aCL, IgG aß2GP1, IgG aß2GP1-D1, IgG aPS/PT. Triple IgG aPL positivity in any combination significantly increased recurrent thrombosis risk.The presence of any type of aPL IgG in both ELISA and CHLA influenced the recurrence rate of thrombosis in APS.Obesity was a significant risk factor for recurrent thrombosis.

Perinatal outcomes in indian women with Antiphospholipid Antibody Syndrome (APS): Five year experience from a tertiary care centre

BackgroundAntiphospholipid Syndrome (APS) is a systemic autoimmune thrombophilic condition characterized by obstetric manifestations, including pregnancy loss, preeclampsia and fetal growth restriction. Early diagnosis and management are key to improve maternal and neonatal outcomes. ObjectiveThe aim of this study is to assess the perinatal outcomes in APS, the development of various adverse pregnancy outcomes (APO), and their association with specific antibody profiles. Material methodsThis observational study was carried out on booked cases of singleton pregnancy and diagnosed cases of primary APS in our High-Risk Pregnancy (HRP) clinic from January 2018 to December 2022 after approval from institutional ethics committee. Forty-three confirmed cases of primary APS were enrolled and started on low-dose aspirin and low-molecular-weight heparin (LMWH) as per the patient's body weight after confirmation of fetal heart activity radiologically until 36 weeks of gestation as a standard of care. ResultsForty patients (93 %) had obstetric APS, and three patients (7 %) had thrombotic APS. During the course of the current pregnancy, adverse pregnancy outcomes (APO) developed in 12 (30 %) out of 40 cases of obstetric APS and in all 3 patients with thrombotic APS. Preeclampsia was seen in 11 (25.5 %), FGR in 12 (27.9 %), and preterm birth in 7 (16.2 %) cases. Patients with an antibody profile showing the presence of Anti-β2 GP-I positivity and ACL positivity had fewer APOs (20 % and 29 %) in comparison to patients with a LA and triple positive antibody profile (55 % and 50 %). ConclusionTreatment of pregnant women with APS causes significant improvement in the live birth rate. The late pregnancy complications like preeclampsia, FGR, and premature birth, occurring despite treatment still remains a challenge and emphasizes the need for stringent antepartum surveillance and timely delivery.

Autoimmune Manifestations in a Cohort of Egyptian COVID-19 Patients

Abstract Introduction COVID-19 infection can result in a range of symptoms, from asymptomatic to severe, requiring intensive care and ventilatory support. Research has explored the association between COVID-19 and autoimmune conditions, including the detection of autoantibodies in COVID-19 patients. However, results are not conclusive, prompting us to conduct a cross-sectional study to evaluate the prevalence of autoimmune rheumatic manifestations in a cohort of Egyptian individuals diagnosed with COVID-19. Methods Ninety individuals with COVID-19 were included in the study. Patients were classified based on WHO criteria and laboratory data was collected. Autoimmune markers (ANA, RF, ACL IgM, ACL IgG) were measured and patients were grouped based on positive and negative results. Correlational analysis was conducted to assess the association between each marker and clinical severity of COVID-19 and autoimmune rheumatological manifestations. Results Of the studied patients, 13.3% had a positive ANA, 15.6% had a positive RF, 8.9% had a positive ACL IgM, and 5.6% had a positive ACL IgG. However, there was no statistically significant difference between severity groups regarding the results of ANA, RF, ACL IgM, and IgG. All patients with a positive ANA were present among severe and critical COVID-19 cases, and all patients with positive RF, ACL IgM, or ACL IgG were among moderate, severe, and critical cases. Conclusion Our study provides insight into the prevalence of autoimmune rheumatic manifestations in COVID-19 patients. While our results were inconclusive regarding the association between autoimmune markers and severity of disease, we found a statistically significant higher prevalence of several symptoms in critical COVID-19 patients. Our study highlights the importance of further investigation into the relationship between COVID-19 and autoimmune conditions.

The association between antiphospholipid syndrome and atrial fibrillation: a single center retrospective case-control study.

Antiphospholipid syndrome (APS) is a systemic autoimmune syndrome characterized by arterial or venous thrombosis, pregnancy complications and thrombocytopenia. The aim of this study is to investigate the association between APS and atrial fibrillation (AF) among patients in Peking University People's Hospital. A single center retrospective study was conducted. Cases were hospitalized patients diagnosed with AF by a cardiologist while the control group patients did not exhibit cardiac diseases. The results of the study revealed that in multivariable logistic regression, APS, anticardiolipin antibody (aCL) positivity and anti-beta-2-glycoprotein antibody (anti-β2GPI) positivity are independent risk factors of AF. APS, aCL positivity and anti-β 2GPI positivity are statistically different between AF patients and non-AF patients. Forthcoming studies are needed to clarify the potential link between APS and AF.

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

The prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated. To determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population. This cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti-beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023. Associations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons. Among the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = -0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA-positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. In this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

Anticardiolipin Antibodies in Patients with Cancer: A Case–Control Study

Antiphospholipid antibodies are highly prevalent in autoimmune diseases and mainly associated with thromboembolic events, which is one of the major reasons for cancer-related mortality. Confirmed adult cancer patients were included (n = 40) with an equal number of age- and sex-matched healthy controls. The presence and concentration of anticardiolipin antibodies were investigated by the enzyme-linked immunosorbent assay using the venous blood samples. aCL antibodies were detected in 60.0% (n = 24) of the cancer patients compared to none in the healthy controls (p < 0.001). The serum concentration of aCL antibodies was significantly higher in cancer patients than controls (p < 0.001) and ranged from 89.0 U/mL to 133.0 U/mL among the aCL-positive patients. All the lung cancer patients (n = 6) were diagnosed with positive aCL, and a borderline significant association of aCL antibody positivity was observed in colon cancer patients (p = 0.051). About 72.7% of the advanced-stage cancer individuals and 81.8% of the cancer patients who underwent surgery were diagnosed with positive aCL antibodies. A significant association of aCL antibody positivity was observed with cancer patients comorbid with heart diseases (p = 0.005). The prevalence and serum levels of aCL antibodies were significantly higher in cancer patients compared to healthy controls. Cancer patients (i.e., lung, liver, and colon), at advanced-stage, comorbid with heart diseases, who underwent surgery, were more likely to be diagnosed with aCL antibodies.

Risk factors for persistent positive anticardiolipin antibodies in women with recurrent pregnancy loss

Antiphospholipid syndrome (APS) is an established cause of recurrent pregnancy loss (RPL). It is necessary to detect persistently positive antiphospholipid antibodies to diagnose APS. This study aimed to explore risk factors for persistent anticardiolipin (aCL) positivity. Women with a history of RPL or with a history of one or more intrauterine fetal deaths after 10 weeks underwent examinations to determine the causes of RPL, including antiphospholipid antibodies. If aCL-IgG or aCL-IgM antibodies were positive, retests were performed at least 12 weeks apart. Risk factors for persistent aCL antibody positivity were retrospectively investigated. The number and percentage of cases above the 99th percentile were 74/2399 (3.1%) for aCL-IgG, and 81/2399 (3.5%) for aCL-IgM. Of the initially tested cases, 2.3% (56/2399) for aCL-IgG and 2.0% (46/2289) for aCL-IgM were ultimately positive above the 99th percentile in retests. Retest values after 12 weeks were significantly lower than the initial values for both IgG and IgM immunoglobulin classes. Initial aCL antibody titers were significantly higher in the persistent-positive group than in the transient-positive group for both IgG and IgM immunoglobulin classes. The cut-off values for predicting persistent positivity of aCL-IgG antibodies and aCL-IgM antibodies were 15 U/mL (99.1 percentile) and 11 U/mL (99.2 percentile), respectively. The only risk factor for persistently positive aCL antibodies is a high antibody titer during the initial test. When the aCL antibody titer in the initial test exceeds the cut-off value, therapeutic strategies can be defined in subsequent pregnancies without waiting for 12 weeks.

The impact of antiphospholipid antibodies in Takayasu arteritis.

The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aβ2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aβ2G1 and/or LA positivity. There were no patients with positive aCL. All aβ2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aβ2G1 (+) had a history of pregnancy loss. Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

The interaction of persistent antiphospholipid antibodies positivity and cigarette smoking is associated with an increased risk of cardiovascular events: Cross-sectional and longitudinal analysis

BackgroundThe antiphospholipid antibody (aPL)-positivity was suggested as a nontraditional risk of coronary artery disease (CAD) and it was associated with cigarette smoking. The co-occurrence of them was usually reported in individuals with cardiovascular diseases. This study was to demonstrate their interaction on the increasing risk of cardiovascular events. Methods and resultsA total of 826 consecutive male individuals who underwent coronary angiography (CAG) /percutaneous coronary intervention (PCI) were prospectively followed and classified into three groups based on different smoking statuses. The current smoking subjects had the highest occurrence of aPL-positivity, including aCL IgM (20.1%) and aβ2GP1 IgM (15.5%). IgM isotype positivity was an independent risk factor of CAD in the multivariate model, OR: 2.70 (1.52–4.80) for aCL IgM and OR:2.50 (1.35–4.63) for aβ2GP1 IgM.The interaction of current smoking and IgM isotype positivity was significantly associated with increased risk of CAD, OR: 8.75(4.59–16.66) for aCL IgM and OR: 8.78(4.28–17.98) for aβ2GP1 IgM. During about 3 years of follow-up, the smoking patients carrying persistent aPL positivity had the highest cumulative incidence of recurrent myocardial infarction and in-stent restenosis after CAD. ConclusionThe interaction of current smoking and IgM isotype positivity was significantly associated with the increased risk of CAD, including positive aCL IgM and aβ2GP1 IgM. Cigarette smoking elevated the risk of subsequent cardiovascular events in the presence of IgM isotype positivity, including recurrent myocardial infarction and in-stent restenosis.

Frequency of positive antiphospholipid antibodies in pregnant women with SARS-CoV-2 infection and impact on pregnancy outcome: A single-center prospective study on 151 pregnancies.

BackgroundAt the beginning of the SARS-CoV-2 pandemic, there was a lack of information about the infection’s impact on pregnancy and capability to induce de novo autoantibodies. It soon became clear that thrombosis was a manifestation of COVID-19, therefore the possible contribution of de novo antiphospholipid antibodies (aPL) raised research interest. We aimed at screening SARS-CoV-2 positive pregnant patients for aPL.MethodsThe study included consecutive pregnant women who were hospitalized in our Obstetric Department between March 2020 and July 2021 for either a symptomatic SARS-CoV-2 infection or for other reasons (obstetric complications, labour, delivery) and found positive at the admission nasopharyngeal swab. All these women underwent the search for aPL by means of Lupus Anticoagulant (LA), IgG/IgM anti-cardiolipin (aCL), IgG/IgM anti-beta2glycoprotein I (aB2GPI). Data about comorbidities, obstetric and neonatal complications were collected.Results151 women were included. Sixteen (11%) were positive for aPL, mostly at low titre. Pneumonia was diagnosed in 20 women (5 with positive aPL) and 5 required ICU admission (2 with positive aPL). Obstetric complications occurred in 10/16 (63%) aPL positive and in 36/135 (27%) negative patients. The occurrence of HELLP syndrome and preeclampsia was significantly associated with positive aPL (p=0,004). One case of maternal thrombosis occurred in an aPL negative woman. aPL positivity was checked after at least 12 weeks in 7/16 women (44%): 3 had become negative; 2 were still positive (1 IgG aB2GPI + IgG aCL; 1 IgM aB2GPI); 1 remained positive for IgG aCL but became negative for aB2GPI; 1 became negative for LA but displayed a new positivity for IgG aCL at high titre.ConclusionsThe frequency of positive aPL in pregnant women with SARS-CoV-2 infection was low in our cohort and similar to the one described in the general obstetric population. aPL mostly presented as single positive, low titre, transient antibodies. The rate of obstetric complications was higher in aPL positive women as compared to negative ones, particularly hypertensive disorders. Causality cannot be excluded; however, other risk factors, including a full-blown picture of COVID-19, may have elicited the pathogenic potential of aPL and contributed themselves to the development of complications.

IgA Antiphospholipid Antibodies in Antiphospholipid Syndrome and Systemic Lupus Erythematosus.

Objective: To define the role of IgA antibodies to cardiolipin (aCL) and IgA antibodies to beta-2 glycoprotein 1 (anti-β2-GP1) in the development of vascular complications in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Material and methods: A total of 187 patients with one of the following diagnoses: primary APS (PAPS), probable APS, SLE with APS, and SLE without APS. The comparison group consisted of 49 patients with other rheumatic diseases (RD), the control group included 100 relatively healthy individuals (without RD, oncological pathology, and infectious diseases). All patients underwent standard clinical, laboratory, and instrumental examinations before being included in the study and during follow-up. The aPL study included the determination of IgG/IgM aCL, IgG/IgM anti-β2-GP1 by enzyme-linked immunosorbent assay (ELISA), IgG/IgM/IgA aCL, IgG/IgM/IgA anti-β2-GP1 by chemiluminescence analysis (CLA), and lupus anticoagulant (LA). Results: IgA aCL were detected in 75 (40%) of the 187 patients with APS and SLE, in none of the comparison group, and in 2 (2%) of the control one. IgA anti-β2-GP1 were detected in 63 (34%) of the 187 patients with APS and SLE, in none of the patients in the comparison group, and in one (1%) of the control group. The prevalence of IgA aCL and IgA anti-β2-GP1 and their levels were statistically significantly higher in patients with APS (PAPS and SLE + APS) than the levels in patients with SLE and those of the comparison and control groups (p < 0.05). IgA aCL and IgA anti-β2-GP1 were significantly associated with thrombosis in APS (χ2 = 4.96; p = 0.02 and χ2 = 4.37; p = 0.04, respectively). The risk of thrombosis was 2.04 times higher in patients with positive IgA aCL than in patients without these antibodies, as well as in patients with positive IgA anti-β2-GP1; it was twice as high as in patients without antibodies. There was a high specificity of IgA aCL and IgA anti-β2-GP1 for both the diagnosis of APS and its clinical manifestations, despite a low sensitivity. Conclusions: The study revealed a relationship of thrombosis and APS with IgA aCL and IgA anti-β2-GP1. There was a high specificity of IgA aCL and IgA anti-β2-GP1 (95% and 93%, respectively) for the diagnosis of APS with a low sensitivity (54% and 44%, respectively). There were no patients with isolated positivity of IgA aCL and IgA anti-β2-GP1.

Anti-phospholipid antibodies in the setting of thromboembolic events associated with severe COVID-19 pneumonia

BackgroundThrombotic consequences have been reported in COVID-19-infected patients, especially those who are critically ill. Multiple studies have tested antiphospholipid antibodies (aPLs) among COVID-19 patients, but to date, the actual frequency of aPLs is still uncharted.In this cohort study, we analyzed the outcomes of 173 consecutive patients with confirmed COVID-19 infection. Anti-phospholipid antibodies, which include anti-cardiolipin antibodies [aCL (IgM), aCL (IgG)], and B2-glycoprotein I antibodies [aβ2GPI (IgM), aβ2GPI (IgG)] were detected by using immunoassays. In contrast, lupus anti-coagulant (LAC) antibodies are identified through a coagulation-based assay.ResultsThe study demonstrated a high incidence of thrombotic consequences in severe COVID pneumonia cases and supported an increased risk of developing aPLs following COVID-19 infection. Pulmonary embolism had the most common prevalence of all thrombotic events. Among the various aPLs tested in thrombotic patients, lupus anti-coagulant (LAC) had the highest positivity (46.2%). Most patients with arterial thromboembolism (stroke, myocardial infarction, limb ischemia, bowel ischemia, and renal artery thrombosis) had triple positivity of anti-phospholipid antibodies. Testing aPLs antibodies after 12 weeks of recovery for survived patients only 2 out of 23 patients had aPLs positivity compared to 35 out of 65 tested during hospital admission. Furthermore, we found no significant changes in aPLs positivity between survived and non-survived patients with thrombotic event.ConclusionsaPLs increased transiently as an inflammatory-mediated condition. Individuals with aPLs triple positivity (positive LAC, aCL, and aB2GPI) had a considerable risk of arterial thromboembolism (ATE).

Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: Untangling the knot

BackgroundAlthough the triple positivity of antiphospholipid antibodies (aPL) is important for classifying high‐risk patients, interpretation of aPL positivity, namely the lupus anticoagulant (LA), anti‐cardiolipin (aCL), and anti‐beta2‐glycoprotein I autoantibodies (aB2GPI) remains challenging for thrombotic risk stratification. ObjectiveTo compare biological and clinical data between triple aPL– and single aCL–positive patients. MethodsOf the 6500 patients assayed for aPL in daily practice within 3 years, we retrospectively analyzed data from 161 patients that were either triple aPL–positive or single aCL–positive with 5 years’ follow‐up for 121 of them. ResultsWhatever triple or single aPL positivity, we found a high prevalence of “carrier” patients (43%), which led us to question the clinical relevance of the triple aPL positivity. This result also justified the need to identify high‐risk profiles. In asymptomatic patients, high risk of thrombotic events is associated with (1) two positive tests for LA or a Rosner Index >27 combined with both aCL‐IgG and aB2GPI‐IgG positivity, (2) persistent single aCL positivity without an associated autoimmune disease. In symptomatic patients, we demonstrated differences in the phenotype of patients and their therapeutic anticoagulation according to the number of positive aPL but we did not find differences in the number of clinical events, recurrence, or relapse, even in the absence of treatment. ConclusionThis study shows that the thrombotic risk does not necessarily increase with the number of positive tests and raises the question of the therapeutic management of single aCL–positive patients.

Management and Outcomes of Women with Antiphospholipid Antibodies or Antiphospholipid Syndrome during Pregnancy

BackgroundPregnant women with antiphospholipid antibodies (aPLs) or antiphospholipid syndrome have an increased risk for thrombosis. Although a combination of low-dose aspirin and unfractionated heparin (UFH) or low molecular weight heparin (LMWH) are usually prescribed in pregnancy, there is no consensus on optimal dosing of these agents. Despite the use of low-dose aspirin and LMWH, approximately 30% of women with a positive lupus anticoagulant (LA), underlying autoimmune disease, or a previous history of thrombosis have unfavorable outcomes.AimTo describe the management and outcomes of women with either aPLs or APS during pregnancy at a university medical center.MethodsWe conducted a retrospective cohort study of pregnant women with either aPLs or APS seen in our hematology clinic in consultation between January 2006 and August 2021. Data collected included demographics, reason for aPLs testing, personal or family history of thrombosis or autoimmune disease, and presence of other thrombophilias. Antiphospholipid antibodies included the LA, anti-cardiolipin (aCL) and anti-beta-2 glycoprotein 1 (ß2GP1) confirmed on two occasions at least 12 weeks apart. Data was collected on antithrombotic agents used during pregnancy, including aspirin, dose of LMWH, UFH and certolizumab. We recorded the following obstetric outcomes: live births, early delivery, fetal loss, early pregnancy loss <10 weeks gestational age (GA), pre-eclampsia, venous thromboembolic events (VTE), arterial thromboembolism (ATE), and post-partum hemorrhage (PPH). We compared management and outcomes in the presence or absence of LA. Statistical comparisons between groups were conducted with the Fisher's exact test.ResultsThere was a total of 202 pregnancies in 62 women with 11% of pregnancies achieved with assisted reproductive techniques. The most common reasons for aPLs testing were pregnancy loss (35%), VTE (23%), and ATE (8%). Antiphospholipid antibody profiles consisted of 56% triple positive, 8% positive LA plus either aCL or anti- ß2GP1, 13% positive LA alone and 22% with either double positive aCL and anti- ß2GP1 or single aCL or anti- ß2GP1. Twenty-tree percent of women had an additional inherited thrombophilia (Table 1). Of the 202 pregnancies, 52% resulted in live births, 20% in pregnancy loss <10 weeks, 12% in pregnancy loss >10 weeks, and 28% were either electively terminated, resulted on an ectopic pregnancy, or the outcome was unknown due to lost to follow up. Antithrombotic therapy was used in 47% of pregnancies: 26% used aspirin and LMWH, 10% used LMWH alone, and 7% used aspirin alone (Table 2). In 10% of pregnancies, patients were transitioned to UFH prior to delivery. Pre-eclampsia with or without HELLP syndrome occurred in 10% of pregnancies and maternal thromboembolic complications occurred in 6%. On analysis of outcomes stratified by LA status, there was a trend toward a higher rate of preterm births in the presence of a positive LA (Table 3). The rate of live births was increased with the use of antithrombotic therapy (Table 4).ConclusionPatients with antiphospholipid antibodies (aPLs) and antiphospholipid syndrome had elevated rates of complications and adverse outcomes during pregnancy. LA positive status was associated with a trend toward a higher rate of preterm births. Further studies are needed to clarify the factors associated with adverse outcomes and optimal anticoagulation management. [Display omitted] DisclosuresDesancho: Sanofi-Genzyme: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure:Certolizumab with the hypothesis of improving clinical outocomes

The Predictive Value of the aCL and Anti-β2GPI at the Time of Acute Deep Vein Thrombosis-A Two-Year Prospective Study.

Antiphospholipid syndrome (APS) is an important cause of deep vein thrombosis (DVT). According to current APS classification criteria, APS cannot be confirmed until 24 weeks after DVT. This time frame results in frequent discontinuation of anticoagulant treatment before APS is diagnosed. Therefore, the aim of our study was to evaluate the potential predictive value of anticardiolipin (aCL) and anti-β2glycoprotein I (anti-β2GPI) before discontinuation of anticoagulation therapy. Patients with newly diagnosed DVT were included into a 24-month prospective study. All patients received anticoagulant therapy. aCL and anti-β2GPI were determined at inclusion and every four weeks for the first 24 weeks and then one and two years after inclusion. APS was confirmed in 24/221 (10.9%) patients. At the time of acute DVT 20/24 (83.3%), APS patients had positive aCL and/or anti-β2GPI. Two patients had low aCL levels and two were negative at the time of acute DVT but later met APS criteria due to lupus anticoagulant (LA). Our data indicate that negative aCL and/or anti-β2GPI at the time of acute DVT make further aPL testing unnecessary; however, LA should be determined after discontinuation of anticoagulant therapy. Positive aCL and/or anti-β2GPI at the time of acute DVT have a strong positive predictive value for APS and may support therapeutic decisions.

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.

Poor Agreement between Commercially Available Anti-Cardiolipin and Anti-β2glycoprotein I IgG and IgM Solid Phase Assays Hampers Uniformity in the Classification of Antiphospholipid Syndrome Patients

The antiphospholipid syndrome (APS) is characterized by thrombosis and/or specific pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPL). Given the high frequency of clinical symptoms irrespective of APS, laboratory tests are of utmost importance for the diagnosis of the disease. Laboratory criteria include aPL detection by a functional assay referred to as lupus anticoagulant (LAC) or by semi-quantitative solid phase assays measuring anti-β2glycoprotein I (aβ2GPI) or anti-cardiolipin (aCL) IgG/IgM antibodies. 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. In a large multicentre study, we aimed to assess the agreement between four solid phase assays measuring IgG and IgM aCL and aβ2GPI aPL.1168 patients were included from eight European centers. Patients were classified by the local centers resulting in 259 thrombotic APS patients, 204 diseased controls for thrombosis, 122 obstetric APS patients, 33 diseased controls for pregnancy complications, 196 patients with autoimmune disease other than APS, 100 pregnant women without complications, 194 patients without clinical and laboratory criteria for APS and 60 APS patients without specification of the clinical condition. Four platforms were selected based on frequency of use and the willingness of manufacturers to provide their assays (Table 1). All samples with all assays were tested at one location by a single technician.To assess the agreement between the four platforms in the detection of IgG/IgM aCL and aβ2GPI aPL Kappa statistics was performed. A Kappa agreement value of 0.40-0.59 implies that only 15-35% of the data are reliable. Low levels of reliability affect diagnosis and treatment of APS patients and are unacceptable for clinical laboratories. In this study a Kappa agreement value of ≥0.8 (“good agreement”) was considered as acceptable. The manufacturer's recommended cut-off value was used upon confirmation in at least 20 healthy donors.Apart from Bioplex versus AcuStar and ImmunoCap EliA versus AcuStar (good agreement) all the other tested platforms did not reach a Kappa value ≥0.80 for aCL IgG and aβ2GPI IgM positivity (Table 2). Only two assays were in good agreement for aβ2GPI IgG positivity (AcuStar versus Bioplex and Quanta Lite ELISA versus ImmunoCap EliA), while all other tested platforms did not reach the threshold value. aCL IgM reactivity showed the lowest level of agreement, resulting in Kappa values <0.80 between the platforms.Additionally, we determined the aPL titer correlation using a Spearman's rank test to be independent of differences in cut-off values. Values below the detection limit were replaced by the lower detection limit value. Apart from AcuStar and Bioplex all the other tested platforms had a Spearman's rank correlation coefficient <0.80 for aβ2GPI IgG, aCL and aβ2GPI IgM positivity (Table 3). None of the tested platforms resulted in a correlation coefficient ≥0.80 for aCL IgG.To assess the clinical implications of the observed (dis)agreements, we investigated the number of patients that would be reclassified from thrombotic APS to non-APS thrombosis and vice versa based on our results. From the 259 thrombotic APS patients, 35 were negative for LAC (determined by the center). From these 35 patients, 18 up to 26 patients tested negative for any aPL in the four included platforms. Additionally, from the 204 non-APS thrombotic patients 1 up to 11 patients were positive for at least one aPL. In case of repetitive positivity, these patients in our hands would be classified as APS patients. Similar data were obtained for obstetric patients, resulting in a possible reclassification of 17 up to 21 patients.Our study clearly indicates that diagnosis of APS is strongly platform dependent. Since APS patients have an increased risk for thrombosis recurrence, misclassification of patients has major implications. Falsely diagnosed patients may be given indefinite oral anticoagulant treatment, thus being exposed to a high risk of bleeding without having any benefit of such treatment. False-negative results have serious consequences as they need long-term anticoagulation to prevent recurrence. Standardization/uniformity of laboratory assays for the diagnosis of APS is therefore urgently warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

POS1238 ANTIPHOSPHOLIPID ANTIBODIES AND COVID-19: TREND OVER TIME

Background:Since the beginning of the SARS-CoV-2 outbreak, antiphospholipid antibodies (aPL), a known thrombotic risk factor, have been studied in COVID-19 patients, in whom thromboembolic events have been associated with poor prognosis. To date, the pathogenetic role of aPL and the trend over time is still unknown.Objectives:Aim of the study was to investigate whether aPL positivity was correlated with thrombosis in COVID-19 patients and whether it was a transient or persistent.Methods:We included all consecutive COVID-19 patients hospitalized at Policlinico Umberto I, Sapienza University of Rome from April 1, 2020 to June 7, 2020. In these patients, serum levels of anti-cardiolipin (aCL) IgM, IgG, IgA, anti-β2glycoprotein I (aβ2GPI) IgM, IgG were measured by enzyme-linked immunosorbent assay (ELISA) and Lupus Anticoagulant (LA) was detected with coagulatory tests in patients not in treatment with anticoagulant drugs.Results:Five out of 73 (6.8%) patients resulted positive for aCL IgM, 3 of them also tested positive for aβ2GPI IgM. aCL IgA were tested positive in 14 out of 46 patients (30.4%). Overall 18 patients resulted positive for at least one test. Seven (9.6%) patients developed thrombotic events during hospitalization, 3 of them resulting positive for aPL (Table 1. below).Table 1.Clinical and demographic features of the 7 Covid-19 patients that presented thrombotic eventsFeaturesPatient 1Patient 2Patient 3Patient 4Patient 5Patient 6Patient 7Age - yr67788343707495SexfemalefemalefemalemalemalefemalemaleMedical HistoryMalignancy, HypertensionStrokeChronic obstructive pulmonary diseaseNo medical historyChronic obstructive pulmonary disease, HypertensionMalignancy,HypertensionInitial findingsSigns and symptomsDyspneaDyspneaDyspneaFever, ageusia/anosmia, chest painFever, coughDyspneaDyspneaHRCT chest: Bilateralground glass opacityyesyesyesyesyesyesyesBaseline laboratory valuesLymphocytecount, cells x 106/L2202102330158016806001390Lactatedehydrogenase, U/L223321199227226349199Ferritin mcg/L6143172133874622455197D-dimer mcg/L7301213291228268812981097PaO2:FIO2, mm Hg132120442534348493314Anticoagulant therapy at the time of the thrombotic eventTherapeutic dosageProphylactic dosageProphylactic dosageNot administeredTherapeutic dosageTherapeutic dosageTherapeutic dosageThrombotic eventsStrokePulmonary embolismPeripheral venous thrombosisMyocardial infarctionPulmonary embolismMyocardial infarction, peripheral arterial thrombosis, peripheral venous thrombosisPeripheral venous thrombosisAntiphospholipid antibodiesnegativeAnti-cardiolipin IgM low title, anti-β2glicoprotein I IgM low titlenegativenegativenegativeAnti-cardiolipin IgM low title, anti-β2glicoprotein I IgM low titleAnti-cardiolipin IgA low titleOutcomeExitusExitusSuicideDischargedDischargedDischargedExitusAntiphospholipid antibodies tested after at least 12 weeksNPNPNPNPNPNegativeNPWe observed that patients showing double positivity for aCL IgM and aβ2GPI IgM had a likelihood positive ratio of 6.3 for thrombotic events (p=0.012) and a likelihood positive ratio of 4.9 for increased D-dimer levels (p=0.027). aCL IgA, the most prevalent aPL in this cohort, was not associated with thrombosis. Of the 18 aPL positive patients, 5 died, 3 were lost to follow-up, and 10 were tested on a second occasion at least 12 weeks, two patients confirmed positivity without clinical signs suggestive of APS.Conclusion:These results suggest that double positivity for aCL and aβ2GPI IgM increases the risk of thrombosis in COVID-19 patients, unlike aCL IgA. APL positivity may be persistent and it is advisable to monitor it over time.Disclosure of Interests:None declared

P028 Aortic thrombosis with persistently positive antiphospholipid antibodies in a patient with COVID-19 pneumonitis

Background/Aims Arterial thrombosis and positive antiphospholipid antibodies have been reported following COVID-19 infection. We report a case of aortic thrombosis occurring after COVID-19 pneumonitis, with persistently positive anticardiolipin antibodies. Methods A 63-year-old lady presented with sudden onset of abdominal pain radiating to the back, associated with vomiting. She reported feeling slightly breathless, and ten days prior to admission a throat swab for SARS-CoV-2 tested positive. Oxygen saturation was 96% (94-100%) on room air. Respiratory examination revealed minimal basal crackles bilaterally. Her heart sounds were normal, and there was no carotid or subclavian bruit. Radial, ulnar, brachial, subclavian and temporal pulses were intact and symmetrical. The abdomen was soft, but tender over the right upper quadrant and epigastrium. Nailfolds were normal, and there was no livedo reticularis and no vasculitic rash. Initial investigations showed a CRP of 235 mg/L (<5), White blood cell count 15.2 x109/L (4.0-11.0), neutrophil count 12.6 x109/L (1.7-7.5). She was reviewed by the surgical team and CT Thorax, Abdomen and Pelvis requested due to the high CRP. Results CT showed a mild COVID pattern pneumonitis, inflammatory changes around the infrarenal aorta containing irregular circumferential clot, raising the suspicion of aortitis. An autoimmune screen was requested with following Results positive IgM Anti-Cardiolipin Antibodies (ACL) at 34.6 U/mL (0.0-20.0), IgG ACL 8.5 U/mL (0.0-20.0), Anti-B2-GP1 (B2GP1) Antibodies negative, Lupus anticoagulant (LAC) was not tested as patient was already on Low Molecular Weight Heparin (LMWH). ANA screen, Anti-ENA screen, ANCA screen, Crithidia Lucillae (dsDNA), RF, Anti-CCP Antibodies, Complement C3 and C4 were all negative. No steroid treatment was commenced. The patient then self-discharged against medical advice and was reviewed as an out-patient. CT scan was reviewed by a vascular radiologist who confirmed the suspicion of aortitis. Subsequently, a 5-Fluorodeoxyglucose-Positron Emission Tomography (FDG PET) CT scan showed no evidence of active, ongoing large vessel vasculitis. A short, linear focus of mild increased FDG uptake associated with some calcification within the left lateral abdominal aortic wall was more typical of atheromatous disease than vasculitis. LMWH was switched to long-term warfarin. She has now fully recovered from COVID and has remained well. Repeat Antiphospholipid screen taken more than 12 weeks later showed a positive IgM ACL (40.2 U/mL), and negative IgG ACL and B2GP1. Once again LAC was not tested as the patient has continued warfarin. IgM ACL positivity following COVID-19 infection has been reported by several other centres. Conclusion Our understanding of the significance of positive antiphospholipid antibodies and COVID-19 infection is evolving. Further research is needed to establish if there is a relationship between COVID-19 infection, thrombosis and positive ACL or if this is an epiphenomenon. Disclosure M. Curuvija: None. K. Hawkins: None. S. Al-Mudhaffer: None. E.P.M. Humphreys: Honoraria; E.H. has participated in advisory board meetings for Pfizer. Other; E.H. has received sponsorship to attend conferences from Abbvie, UCB and Celgene.

Location of recurrent cardiovascular events and anticardiolipin antibodies.

The relationship between anticardiolipin (aCL) antibodies and cardiovascular events is uncertain and may vary according to arterial location. FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral artery disease (PAD). The rate of subsequent ischaemic events was cross-referenced with the presence of aCL antibodies (any isotype, IgG or IgM). As of June 2017, 1387 stable outpatients were recruited. Of these, 120 (8.7%) showed positive levels of aCL antibodies. Over an average follow-up of 18months, 250 patients developed subsequent events: 101 myocardial infarction, 57 ischaemic stroke and 92 critical leg events. Patients with positive aCL antibodies had a higher risk of distal artery events (a composite of ischaemic stroke or critical leg events) than patients with undetectable or low levels (rate ratio: 1.66; 95% CI: 1.07-2.60). However, an association with central coronary events was not found. The multivariate Cox analysis after adjustment for relevant clinical covariates showed that positivity of aCL antibodies is an independent risk factor for distal events (hazard ratio: 1.60; 95% CI: 1.01-2.55; P<.05). Positivity of aCL antibodies is associated with an increased risk of subsequent distal artery ischaemic events (cerebral or leg arteries) but not coronary artery events. Anticardiolipin antibodies appear to have a different relationship on the localisation of ischaemic events in patients with symptomatic artery disease.