Presence Of Antiphospholipid Antibodies Research Articles

Pathogenetic significance of antiphospholipid antibodies in the development of placenta-associated complications in pregnant women with thrombocytopenia

BACKGROUND: Thrombocytopenia is one of the most common cytopenic syndromes that complicate pregnancy. It is considered a typical hematological criterion and the second most common manifestation of antiphospholipid syndrome. In recent years, the relationship between the development of thrombotic and placenta-associated pregnancy complications and the circulation of antiphospholipid antibodies has been actively studied, which makes it necessary to search for new methods for hemostasis correction and for prevention of the development of obstetric complications.
 AIM: The aim of this study was to assess the incidence of antiphospholipid antibodies in pregnant women with thrombocytopenia in order to determine the risk of obstetric complications and adverse pregnancy outcomes depending on the presence of antiphospholipid antibodies in the examined women.
 MATERIALS AND METHODS: 299 pregnant women were included in this multicenter prospective study: the main study group (n = 249) consisted of patients with thrombocytopenia, and the control group (n = 50) comprised women with normal platelet counts during a physiological pregnancy. All participants underwent a complete clinical and anamnestic examination and a study of the hemostasis system. To determine antibodies to cardiolipin, beta-2 glycoprotein 1, annexin V, and prothrombin (IgG/IgM/IgA), we performed enzyme-linked immunosorbent assay in 84 pregnant women with thrombocytopenia and in 25 women in the control group. Lupus anticoagulant was determined in 123 pregnant women of the main group and 25 women in the control group using an ACL-200 coagulometer (Instrumentation Laboratory, Spain).
 RESULTS: A comparative analysis of antiphospholipid antibodies detection has shown that in pregnant women with thrombocytopenia, lupus anticoagulant was detected in every third case (35.8% of cases, 44/123 women), which is more common than in the control group (8.0% of cases, 2/25 women; p = 0.008). Antibodies to beta-2 glycoprotein 1 were detected in pregnant women with thrombocytopenia in every fourth case (27.4% of cases, 23/84 women), and in the control group only in 4% of cases (1/25 women; p = 0.013). Antibodies to cardiolipin were also more often detected in pregnant women with thrombocytopenia (23.8% of cases, 20/84 women) compared to the control group (4% of cases, 1/25 women; p = 0.040). Based on the data obtained with V Cramer, we established medium-strength direct correlations between criterial antiphospholipid antibodies circulation and the development of placenta-associated complications of pregnancy (p 0.05; 0.2 V 0.4). We also identified statistically significant risks of developing placenta-associated complications in pregnant women with circulating antiphospholipid antibodies (95 % confidence interval excludes 1).
 CONCLUSIONS: Thrombocytopenia during pregnancy develops more often in women with antiphospholipid antibodies. Antiphospholipid antibodies circulation elevates coagulation potential and activates intravascular coagulation, resulting in an increased risk of placenta-associated complications of pregnancy, which requires hemostasis correction.

Secondary antiphospholipid syndrome in systemic lupus erythematosus – screening, diagnosis and treatment methods

Systemic Lupus Erythematosus is the hallmark of autoimmune diseases, being characterized by multiple organ involvements and immune abnormalities, amongst which the presence of antiphospholipid antibodies with or without specific clinical manifestations (vascular thromboses and pregnancy morbidities) has a significant impact on the disease course, both short and long term, causing the accumulation of irreversible damage. This study evaluates the aforementioned impact, highlighting the importance of very early screening for these antibodies.

P-371 The role of pharmacogenetics for individualized adjuvant therapy in patients with recurrent implantation failures

Abstract Study question In women with recurrent implantation failure (RIF), could we improve IVF/ICSI outcomes after administration of appropriate adjuvant therapies depending on patient's genetic profile?. Summary answer In RIF patients carrying polymorphisms detected in p53, IL-11 and VEGF genes, the addition of aspirin and intralipids administration appears to be beneficial. What is known already RIF is a distressing phenomenon of obscure etiology. Among the putative factors associated with this condition, we have immunological factors (the presence of antiphospholipid antibodies, certain cytokines or NK cells in maternal serum), genetic alterations in the parents or embryos, uterine abnormalities, or the presence of endometritis. Recently, certain genetic polymorphisms in genes involved in embryo implantation mechanisms at the endometrial (p53 and VEGF), immunological (IL-11 and Apo-E) and thrombotic levels (F5, F2 and MTHFR) have been identified. Study design, size, duration 104 IVF cycles (2017-2021), corresponding to ninety-eight patients, were included in this retrospective study. RIF was defined as the failure of achieving an on-going pregnancy after the transfer of at least three good-quality embryos. Exclusion criteria were abnormal karyotype or sperm FISH, uterine malformations, or positive antiphospholipid antibodies. During the index cycle, these patients received different adjuvant therapies; the following were analyzed: hydroxychloroquine, intrauterine hCG instillation, scratching, intralipids, corticosteroids, aspirin, and low molecular weight heparin. Participants/materials, setting, methods To carry out the genetic profile, different SNPs were analyzed in p53 (rs1042522), VEGF (rs1570360), IL-11 (rs11668344), Apo-E (rs429358 and rs7412), F5 (rs6025), F2 (rs199963) and MTHFR (rs1801133 and rs1801131) genes.Taqman® Life Technologies allelic discrimination real-time-PCR and TRP-PLUS kit were used for the detection of the different alleles. The following IVF outcome variables were considered: positive b-hCG, clinical (gestational sac) and on-going (10 week) pregnancy rate. SPSSv20.0 was used for statistical analysis. Main results and the role of chance Polymorphisms associated with a higher risk for RIF were PR and PP genotype for p53 gene, GG for VEGF, GG for IL-11, E4 isoform for Apo-E, GA and AA for F5, GA and AA F2, TT and CC for MTHFR gene. Accordingly, 64% of patients included in our study showed a high-risk genetic profile for RIF. Genotype variants for p53, IL-11 and VEGF were the most prevalent among this population. A multivariate binary logistic regression for possible confounding factors (maternal age, embryo quality, oocyte origin, number of embryos transferred, PGT-A and other adjuvants treatments) showed that those patients with PR/PP genotype for p53, GG for VEGF and GG for IL-11, obtained significantly higher positive b-hCG, clinical and on-going pregnancy rates when aspirin was administered compared to other genotypes (p < 0.05). Furthermore, patients with GG genotype for VEGF, also obtained a significant improvement in positive b-hCG and clinical pregnancy rates after intralipids administration (p < 0.05). None of the other adjuvant treatments employed showed significant differences regardless of the genetic profile. Limitations, reasons for caution The inherent limitations of a retrospective analysis of a limited sample size. Wider implications of the findings IVF/ICSI outcome of RIF patients was analyzed according to the adjuvant treatment received and considering their genetic profile. Pharmacogenetics seems promising in identifying patients at high risk for RIF and may add in the optimization of specific pharmacotherapy depending on the genetic background of each infertile woman. Trial registration number not applicable

Serum antiphospholipid antibody status may not be associated with the pregnancy outcomes of patients undergoing in vitro fertilization.

Antiphospholipid syndrome (APS) is an autoimmune disease that is associated with recurrent pregnancy loss. It is still controversial whether the presence of antiphospholipid antibodies (aPL) in the serum of patients with in vitro fertilization-embryo transfer (IVF-ET) has a negative effect on the outcomes. In view of the discrepancies, a meta-analysis of the published data was performed to explore the relationship of aPL and IVF-ET outcomes. We searched for all published articles indexed in PubMed, Web of Science, and Cochrane Library, which were retrieved up to April, 2021. A total of 921 studies were yielded, of which 6 finally met the inclusion criteria. We carried out the meta-analysis by pooling results of these studies with Review Manager 5.3 software. The effect index was measured with 95% confidence intervals (CIs) of the relative risks (RRs). Six eligible studies were included in this meta-analysis, involving 3214 patients. Our results showed that positive aPL was not associated with decreased clinical pregnancy rate (RR 0.97; 95% CI 0.91-1.04). There was no correlation between positive aPL and increased miscarriage risk (RR 1.22; 95% CI 0.94-1.58). Only 5 of the 6 studies referred to live birth rate, but still no association was found between them (RR 0.95; 95% CI 0.81-1.11). The results showed that the presence of positive aPL neither decreased clinical pregnancy rate and live birth rate, nor increased miscarriage rate in women undergoing IVF, which is differed from the opinion of clinical practice. More prospective studies with high quality and larger sample size are needed to evaluate the relationship between positive aPL and outcomes of IVF-ET.

Non-criteria manifestations in the presence of antiphospholipid antibodies in a paediatric cohort.

To identify the variables associated with the development of non-criteria manifestations in the presence of antiphospholipid antibodies (aPLs) in a paediatric cohort. Multicentric historical cohort study of children under the age of 18 years to determine thrombotic events (TEs) and non-criteria manifestations in the presence of aPL. Eighty-two children were included; 8.5% had at least one TE and 69.5% at least one non-criteria manifestation. Of them, 96.5% did not associate TEs. Haematological manifestations were the most frequent (43.65%), followed by cutaneous (22%), neurological (15.9%) and cardiac (4.9%) events. The most frequent aPLs were: 77.8% LA; 42.7% aCL and 41.5% aβ2GP. The positivity rate was: 64.6% simple, 18.3% double and 17.1% triple. ANA positivity was 68.1%. A bivariate analysis revealed that children with IgM aCL+, IgM aβ2GP+, ANA+, an SLE diagnosis or the absence of TEs had a significantly higher percentage of non-criteria manifestations (P<0.05). The logistic regression showed family history of autoimmune diseases [odds ratio (OR) 4.26, 95% CI: 0.8, 22.2, P=0.086] and the absence of TEs (OR 17.18, 95% CI: 1.2, 244.6, P=0.03) as independent risk factors of developing non-criteria manifestations. An SLE diagnosis, aPL profile and ANA+ were not identified. Non-criteria manifestations were more frequent than TEs. A positive family history of autoimmune diseases and the absence of TEs were associated with a higher risk of developing non-criteria manifestations. Therefore, their inclusion as APS classification criteria should be considered in order to get an improved prognosis in the paediatric population.

Clinical and pathophysiological features of stroke in patients with COVID-19

To study of modern literature on the clinical and pathophysiological features of stroke in patients with a new coronavirus infection (COVID-19). Published data were searched in the electronic databases Medline (PubMed) and eLIBRARY for the period 2019-2022. It has been shown that patients with COVID-19 have a large number of risk factors for stroke, which may indicate that COVID-19 is a trigger for the development of the disease. Stroke predominantly occurs in 10-14 days after the onset of COVID-19, i.e. there was a delayed manifestation. Patients with stroke due to a COVID-19 are characterized by occlusion of large vessels or vessels, in which occlusion occurs extremely rarely, as well as the presence of several lesions. Specific laboratory signs are coagulopathy, the presence of antiphospholipid antibodies, as well as impaired liver and kidney function. This cohort of patients is characterized by high mortality and poor functional outcome (in more than 70% of cases). The pathogenetic mechanism underlying stroke has not been established yet, however, in patients with COVID-19, the activation of a cascade of blood coagulation and thrombosis reactions is recorded. Suppression of ACE2 due to the affinity of its receptors for the COVID-19 virus probably also plays a role in the pathogenesis of stroke, since when the virus enters the body, an imbalance of the renin-angiotensin system develops. COVID-19 can lead to the development of various neurological diseases, including stroke. Further researches are needed to study neuropathogenesis of COVID-19 and the impact of virus SARS-CoV-2 on disease progression.

COVID-19 infection complicated by priapism

SARS-CoV-2 infections are accompanied by a high incidence of thromboembolic events. The infection is responsible for endothelial injury, with frequent presence of anti-phospholipid antibodies and a pro thrombotic state. All of these manifestations lead to localized thrombosis mainly in the lungs and much more rarely to arterial thrombosis. We report the case of a 67-year-old patient who presented to the emergency room for priapism complicating a Covid-19 infection.

Epidemiology, Evaluation and Management of Anti-Phospholipid Syndrome

Antiphospholipid syndrome is defined as the presence of antiphospholipid antibodies in the setting of thrombosis and/or pregnancy loss (APLS).Antiphospholipid syndrome (APS) is an autoimmune thromboinflammatory condition that affects individuals and their families in a negative and often fatal way. There are the two types of APS: Primary APS, which develops on its own, and secondary APS, which is linked to another autoimmune disorder, most often systemic lupus erythematosus (SLE). The HLA-DR7, DR4, DRw53, DQw7, and C4 null alleles have all been linked to APLS. APS is frequently misdiagnosed due to clinical diversity and a lack of diagnostic test consistency. The classification criteria were created to categorise APS patients for research reasons, but they can also be used by professionals to establish diagnoses. Unprovoked thrombosis is currently treated with long-term warfarin or another vitamin K antagonist drug. To avoid obstetric complications, low-dose aspirin and prophylactic heparin, primarily low-molecular-weight heparin, are utilised.In this article we’ll be looking at Anti-phospholipid Syndrome, it’s etiology, epidemiology, evaluation and management.

Determination of the Risk Factors Contributing to the Development of Neuropsychiatric Lupus in a Systemic Lupus Erythematosus Cohort.

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex, varied clinical presentation that is both more common and has poor outcomes in women of color. SLE outcomes also seem to be influenced by socioeconomic factors. Neuropsychiatric lupus (NPL) is a common manifestation of SLE that is difficult to diagnose and treat and has poor clinical outcomes. There is no clear relationship between NPL and SLE-related autoantibodies, and this contributes to the difficulty in diagnosing NPL. As a result, NPL is a significant contributor to morbidity and mortality in patients with SLE.ObjectiveThe purpose of this study was to examine the relationship between serological and socioeconomic factors in the development of NPL in our patient cohort and determine the risk factors for the development of NPL.MethodsThis was an SLE single-center, retrospective chart review study that was performed at a university-based tertiary referral center. Patients aged 18 and older who meet the American College of Rheumatology (ACR) 1997 criteria and were seen between June 1st, 2015, and June 1st, 2019, were included in this study. Overall, 629 patients with SLE were identified, and 263 patients were included. Demographic and serological data were collected. Supplemental socioeconomic information for each zip code in Southwest Virginia was obtained from the United States Government Census website. Continuous variables were analyzed using the T-test or Mann-Whitney U test. Categorical variables were analyzed using chi-square tests or Fisher’s exact tests. Statistical analysis was performed using SAS9.4, and p-value < 0.05 was considered statistically significant.ResultsWe reviewed a number of risk factors including age, sex, race, and median household income (MHI), noting no statistical relationship between these factors and the diagnosis of NPL. We did find that the presence of antiphospholipid antibodies (aPL) was significantly associated with a diagnosis of NPL and that complement 4 (C4) levels trended toward statistical significance.ConclusionIn our cohort of patients, there was no relationship between age, sex, race, and median household income, and the diagnosis of NPL. There was a statistically significant relationship between aPL and the diagnosis of NPL. Other SLE-related antibodies showed no statistical relationship with the diagnosis of NPL. Although not statistically significant, there was a trend toward significance between complement 4 (C4) levels and the diagnosis of NPL.

Abstract 13625: Association of Antiphospholipid Antibodies With Venous Thromboembolism in COVID-19

Introduction: Coagulation abnormalities leading to arterial and venous thrombotic events have been described in patients with COVID-19 and studies have reported an overall pooled incidence of venous thromboembolism (VTE) of 17%, however little is known regarding VTE association with antiphospholipid antibodies in patients with COVID-19. Hypothesis: Antiphospholipid antibodies are associated with VTE events in COVID-19. Methods: This is a retrospective cohort study of COVID-19 patients hospitalized at the University of Virginia Medical Center (UVA). Serum samples were collected and stored in the UVA COVID-19 biorepository. Anti-cardiolipin (aCL) and anti-b2glycoprotein1(ab2GLP1), IgM/IgG titres, were measured from stored samples, using the enzyme-linked immunosorbent assay (ELISA). Specimens were analysed at two distinct time-points/days during the patient’s hospitalization for COVID-19. VTE incidence was collected retrospectively by chart review. The study was approved by the Institutional Review Board at UVA. Two-tailed Mann-Whitney two-sample rank-sum tests were conducted to examine whether there were significant differences in APS antibody levels, and mean change in APS levels between the two time points analysed, and VTE events. Additionally, logistic regression models were constructed to examine whether APS antibody levels and mean change in APS levels had a significant effect on the odds of observing a case of VTE. Results: There were 53 patients included in the study. The mean age of participants was 57.2 years (SD 13.9). VTE did not corelate with the levels of APS at studied time points, or the mean change in APS levels during the disease course. aCL IgM (p = 0.24), aCL IgG (p = 0.92), ab2GLP1 IgM (p = 0.79), and ab2GLP1 IgG (p = 0.79). Changes in the APS antibody levels during the course of the disease were not predictive of the odds of having VTE. Similarly, these changes did not predict the need for ICU care. Conclusions: This study shows that neither the presence of antiphospholipid antibodies nor the change in APS levels during the course of COVID-19 correlated with VTE events.

Antiphospholipid Antibody Profiles and Thrombotic Outcomes in the Starlet Cohort of Patients with Systemic Lupus Erythematosus

IntroductionAntiphospholipid syndrome (APS) is an autoimmune condition characterized by the presence of antiphospholipid antibodies (aPL) and clinical outcomes of thrombosis and obstetric morbidity. APS is more common in patients with systemic lupus erythematous (SLE), with persistently positive aPLs being found in 20-30% of SLE patients. The revised Sapporo lab criteria for APS includes one or more of a positive lupus anticoagulant (LAC), anti-beta 2 glycoprotein 1 (aβ2GP1), or anticardiolipin (aCL). Antibodies must be persistently positive at >99 th percentile over at least 12 weeks (Miyakis et al. J Thromb Haemost, 2006). IgG anti-phosphatidylserine/prothrombin complex (aPS/PT), IgM aPS/PT, and IgG anti-domain 1β2GP1 (aD1β2GP1) are novel aPLs that have been associated with thrombosis, however, conclusive data is still lacking, and it remains unclear how best to incorporate these novel autoantibodies into clinical decision making. The aims of this study were to assess whether the non-criteria IgG aPS/PT, IgM aPS/PT, or IgG aD1 β2GP1 were associated with an increased risk of a first-time thrombotic event in SLE patients. By better understanding the risk of thrombosis in patients with novel aPLs, independent of their association with established criteria aPLs, we can better counsel patients on individual risk of thrombosis.MethodsA retrospective chart review was performed on all participants enrolled in the SouThern Alberta Registry for Lupus EryThematosus (STARLET) database. STARLET is a prevalent cohort of 348 adult patients fulfilling American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. Serology results for LAC, IgG aCL, IgG aβ2GP1, IgG aPS/PT, IgM aPS/PT, and IgG aD1β2GP1 were recorded over the patient's disease course. Anti-PS/PT antibodies were measured by an enzyme-linked immunosorbent assay and IgG aD1β2GP1 by a chemiluminescence immunoassay. Electronic medical records were reviewed from March 2006 to January 2021 for first-time objectively confirmed venous, arterial, and small vessel thrombotic events, as defined by the revised Sapporo criteria. Libman-Sacks endocarditis, livedo reticularis, superficial vein thrombosis and transient ischemic attacks were not included as thrombotic events. Discrepancies in outcomes were resolved by consensus.ResultsAmong patients in the STARLET database, 91.8% were women, 65.5% were White, and the mean age was 42.7 (SD 15). Of 348 patients, 60 (17%) met the revised Sapporo lab criteria, and of those 30 (50%) had a thrombotic event. Among patients who met the revised Sapporo lab criteria, there was an increased risk of thrombosis (OR 3.7, 95% CI, 2.1-6.6).Among the 143 patients that had at least one positive non-criteria autoantibody, 46 (32.2%) had a thrombotic event (OR 1.6, 95% CI 0.97-2.6) (Table 1). Univariate analysis for the association between each non-criteria antibody type and thrombosis are presented in Table 1.There were statistically significant correlations between the revised Sapporo criteria aPLs and non-criteria aPLs; the IgG aPS/PT had a stronger correlation to LAC (Spearman=0.47) than the IgM aPS/PT (Spearman=0.38) (Table 2).In a multivariate analysis that controlled for age, sex, and meeting the revised Sapporo lab criteria, only the non-criteria antibody IgG aPS/PT was associated with an increased risk of thrombosis with an OR of 2.8 (95% CI, 1.3-6.0) (Table 3). There were 35 patients in our cohort that did not meet revised Sapporo lab criteria that had a positive IgG aPS/PT and of these patients 8 (22.9%) had a thrombotic event.ConclusionsIn this cohort of SLE patients, IgG aPS/PT and IgG aD1 β2GP1 were associated with an increased risk of thrombosis, and both antibodies were correlated with previously established aPLs. In our multivariate analysis, only the IgG aPS/PT non-criteria antibody was associated with an increased risk of thrombosis, independent of revised Sapporo criteria aPLs, with an OR of 2.8 (95% CI, 1.3-6.0). Not all patients in the STARLET database had non-criteria aPL autoantibodies measured, and so a smaller sample size may have affected our ability to detect associations with thrombosis. Given the limited data in the area, this valuable information can help inform clinician and patient decision making and provide further guidance on the role of non-criteria antibody testing for patients with SLE. [Display omitted] DisclosuresBarber: AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Sanofi Genzyme: Consultancy, Honoraria. Fritzler: MitogenDx Laboratory: Current Employment; Werfen International: Consultancy; Aesku Group: Consultancy; Alexion Canada: Consultancy. Skeith: CSL Behring: Research Funding; Leo Pharma: Honoraria; Sanofi: Honoraria.

ANTICARDIOLIPINIC ANTIBODIES IN NON-HODGKIN LYMPHOMA

Identification of hemostasis changes in patients with non-Hodgkin's lymphoma (NHL) and anticardiolipin antibodies (aCL). The study included 83 patients (men-34, women-49) with a mean age of 63.2 years, with NHL, investigated complex, by research of lupus anticoagulant (LA) by Turbidimetry; antiβ2glycoprotein I IgG, IgM and aCL antibodies, by ELISA method. Hemostasis disorders were evaluated according to the type of NHL, stage, tumor size. aCL were detected in 10 (12%) patients: 6 patients with aggressive type lymphoma and 4 patients with indolent type lymphoma, with advanced stage B cell NHL in 60%, mean age 52.8 years. LA was present in 80% of cases, unlike aCL IgG antibodies (10%) and antiβ2glycoprotein I IgG (10%). Hemostasis disorders were found in 6 (60%) patients: thrombotic events-at 4 (40%) patients with Mantle cell lymphoma (1 patient), Small lymphocytic lymphoma (1 patient), lymphoblastic lymphoma (2 patients). Local stage (I and II) of the lymphoma was in 75%, but with a large size of the tumor (&gt; 11 cm), and hemorrhage at 2 (20%) patients with stage IV Small lymphocytic lymphoma, in which immune thrombocytopenia developed. The presence of antiphospholipid antibodies, in particular of lupus anticoagulant, advanced age, generalized stage, and large tumor size are risk factors for the development of hemostasis diseases in NHL patients, especially thrombosis.

THE PARADOXICAL PRESENTATION OF PRE-ECLAMPSIA WITH DIFFUSE ALVEOLAR HEMORRHAGE AND VENOUS THROMBOSIS AS CLINICAL MANIFESTATIONS OF ANTIPHOSPHOLIPID SYNDROME

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Antiphospholipid Syndrome (APS) is an autoimmune disorder clinically defined by the presence of antiphospholipid antibodies (aPL), history of arterial or deep venous thrombosis (DVT), and/or repeat episodes of early pregnancy loss. Due to the increased risk for thrombosis, often overlooked is a rare and seemingly paradoxical association between APS and diffuse alveolar hemorrhage (DAH) - a disorder characterized by non-localized alveolar bleeding. Rare manifestation of APS presenting with preeclampsia, DAH, and DVT offers a variety of multi-disciplinary challenges. CASE PRESENTATION: A 34-year-old G6P3 woman at 28 weeks gestation with a remote history of pulmonary embolism (PE), presented to the Emergency Department with a two-day history of dyspnea and hemoptysis. Exam was remarkable for sinus tachycardia, grade 3 systolic murmur at the apex, and increased work of breathing with bilateral pulmonary rhonchi. Computed tomography (CT) scan demonstrated centrally predominant opacities without signs of PE. Bronchoscopy was significant for diffusely hemorrhagic airways with progressively hemorrhagic serial lavage aliquots. Emergent delivery was performed in the setting of Preeclampsia while high-dose steroids were administered for DAH. The patient returned to baseline over the next 3 days without returning signs of hemoptysis. Lupus anticoagulant was positive but PT and PTT were both normal. Steroids were discontinued and therapeutic enoxaparin was started for a possible novel diagnosis of APS.Six days later, she reexhibited hemoptysis. Repeat CT revealed bilateral alveolar infiltrates consistent with the recurrence of DAH. Disproportionate left lower extremity edema and a femoral vein DVT were also discovered. Anticoagulation was again withheld, high-dose steroids were re-started, and an inferior vena cava filter was placed. Repeat lupus anticoagulant testing was positive. In addition, the dilute russell viper venom time (DRVV) was prolonged in the setting of normal PT/PTT, confirming APS diagnosis. She recovered within five days and was prescribed warfarin for chronic anticoagulation, glucocorticoids were tapered, while rituximab infusions were initiated as glucocorticoid-sparing therapy. DISCUSSION: This case highlights challenges associated with the diagnosis and management of rare simultaneous manifestations of APS. In particular, the management of DAH in this scenario is unique because unlike the glucocorticoid-responsive antibodies of ANCA-associated vasculitides, aPL are not known to cause alveolar capillaritis; therefore, the role of steroids is unclear. CONCLUSIONS: Chronic anticoagulation is an absolute requirement for long-term management of APS. Yet as this case exemplifies, in the case of concomitant DAH, administration of glucocorticoids, and subsequently glucocorticoid-sparing immunosuppression is recommended as the safest approach to avoid life-threatening hemorrhage. REFERENCE #1: Cartin-Ceba R, Peikert T, Ashrani A, Keogh K, Wylam ME, Ytterberg S, Specks U. Primary antiphospholipid syndrome-associated diffuse alveolar hemorrhage. Arthritis Care Res (Hoboken). 2014 Feb;66(2):301-10. doi: 10.1002/acr.22109. PMID: 23983016. REFERENCE #2: Stoots SA, Lief L, Erkan D. Clinical Insights into Diffuse Alveolar Hemorrhage in Antiphospholipid Syndrome. Curr Rheumatol Rep. 2019 Sep 6;21(10):56. doi: 10.1007/s11926-019-0852-7. PMID: 31493005; PMCID: PMC7102334. REFERENCE #3: Janowiak P, Sieminska A, Porzezinska M, Smolenska Z, Suchanek H, Jassem E. Difficulties in the treatment of recurring diffuse alveolar hemorrhage accompanying primary antiphospholipid syndrome: a case report and literature review. Adv Respir Med. 2018;86(3). doi: 10.5603/ARM.2018.0020. PMID: 29960279. DISCLOSURES: No relevant relationships by Eric Knott, source=Web Response no disclosure on file for Eric Lang; No relevant relationships by Claudia Saborit, source=Web Response

Кардиоваскулярные манифестации у пациентов с антифосфолипидным синдромом: вопросы диагностики и менеджмента

Антифосфолипидный синдром (AФС) представляет собой аутоиммунное системное заболевание, характеризующееся рецидивирующими тромботическими событиями и/или патологией беременности, ассоциированное с наличием антифосфолипидных антител (aФЛ-АТ). Другие возможные клинические проявления, ассоциированные аФЛ-АТ, представлены вовлечением сердечно-сосудистой системы. Патогенетические особенности этого клинического состояния иммунологически опосредованы и/или связаны с повышенным риском тромбообразования и могут быть объяснены такими механизмами, как воспаление, активация комплемента и тромбоцитов. Вовлечения сердечно-сосудистой системы при АФС включают широкий спектр клинических проявлений: аномалии клапанов (небактериальные вегетации, утолщение их и дисфункция), ишемическую болезнь сердца, внутрисердечный тромбоз и ускоренный коронарный атеросклероз. Кроме того, АФС также может вызвать повреждение миокарда, легочную артериальную гипертензию, дисфункцию левого и правого желудочка. Среди всего этого спектра вовлечение клапанов является наиболее распространенным проявлением кардиоваскулярной патологии у пациентов с АФС и составляет около 30 %. Из-за высокой распространенности вовлечения сердца при АФС клиницисты должны знать об этой патологии с целью уменьшения частоты сердечно-сосудистых осложнений, а профилактические стратегии должны быть сбалансированы на основе глобального профиля риска развития сердечно-сосудистых заболеваний.

Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed.

Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement (p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings (p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041-7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065-1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Prevalence and clinical significance of antiphospholipid antibodies among hospitalized COVID-19 patients

Objective: To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19 (COVID-19) and to find potential associations between antiphospholipid antibody positivity and clinical outcomes. Methods: From September to November 2020, clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang, Indonesia. Antiphospholipid antibodies were measured by finding IgM anti-β2 glycoprotein, lupus anticoagulant, and IgM/IgG anticardiolipin. Clinical characteristics, thrombotic events, ICU admission, and mortality during hospitalization were recorded. Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19, Indonesia. Results: Among 50 patients, 5 patients (10.0%) were positive for antiphospholipid antibodies: 4 patients (80.0%) had IgM anti-β2 glycoprotein and 1 patient had IgG anti-cardiolipin (20.0%) and IgM anti-cardiolipin (20.0%), none of lupus anticoagulant was detected. Antiphospholipid antibodies were associated with anosmia (OR 8.1; 95% CI 1.1-57.9; P=0.018), nausea and vomiting (OR 12.4; 95% CI 1.2-122.6; P=0.010), diarrhea (OR 9.8; 95% CI 1.3-70.9; P=0.010), cardiovascular disease (OR 1.4; 95% CI 1.0-1.9; P=0.001), chronic kidney disease (OR 12.0; 95% CI 1.6-90.1; P=0.05), acute coronary syndrome (OR 29.3; 95% CI 2.0-423.7; P=0.001), moderate (OR 0.11; 95% CI 0.01-1.10; P=0.031) and severe (OR 18.5; 95% CI 1.8-188.4; P=0.002) disease severity, and in-hospital mortality (OR 8.1; 95% CI 1.1-57.9; P=0.018). However, there is no correlation between the presence of antiphospholipid antibody and ICU admission. Conclusions: In summary, the prevalence of antiphospholipid antibodies in COVID-19 patients is low, mainly against IgM anticardiolipin, and is associated with an acute coronary syndrome, gastrointestinal manifestations, moderate and severe disease severity, and increased risk of mortality.

Inactivated SARS-CoV-2 vaccine does not influence the profile of prothrombotic antibody nor increase the risk of thrombosis in a prospective Chinese cohort

The presence of antiphospholipid antibodies was shown to be associated with thrombosis in coronavirus disease 2019 (COVID-19) patients. Recently, according to reports from several studies, the vaccine-induced immune thrombotic thrombocytopenia is mediated by anti-platelet factor 4 (PF4)-polyanion complex in adenovirus-vectored COVID-19 vaccine recipients. It is impendent to explore whether inactivated COVID-19 vaccine widely used in China influences prothrombotic autoantibody production and induces thrombosis. In this prospective study, we recruited 406 healthcare workers who received two doses, 21 days apart, of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBP-CorV, Sinopharm). Paired blood samples taken before vaccination and four weeks after the second vaccination were used in detecting prothrombotic autoantibodies, including anticardiolipin (aCL), anti-β2 glycoprotein I (aβ2GP1), anti-phosphatidylserine/prothrombin (aPS/PT), and anti-PF4-heparin. The seroconversion rate of SARS-CoV-2 specific antibodies was 95.81% (389/406) four weeks after vaccination. None of the subjects had spontaneous thrombosis or thrombocytopenia over a minimum follow-up period of eight weeks. There was no significant difference in the presence of all ten autoantibodies between samples collected before and after vaccination: for aCL, IgG (7 vs. 8, P = 0.76), IgM (41 vs. 44, P = 0.73), IgA (4 vs. 4, P = 1.00); anti-β2GP1, IgG (7 vs. 6, P = 0.78), IgM (6 vs. 5, P = 0.76), IgA (3 vs. 5, P = 0.72); aPS/PT IgG (0 vs. 0, P = 1.00), IgM (6 vs. 5, P = 0.76); aPF4-heparin (2 vs. 7, P = 0.18), and antinuclear antibody (ANA) (18 vs. 21, P = 0.62). Notably, seven cases presented with anti-PF4-heparin antibodies (range: 1.18–1.79 U/mL) after vaccination, and none of them exhibited any sign of thrombotic disorder. In conclusion, inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibody and anti-PF4-heparin antibody nor increase the risk of thrombosis.

Anti-Phospholipid Antibodies and COVID-19 Thrombosis: A Co-Star, Not a Supporting Actor.

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.

Direct Oral Anticoagulants in Anti-Phospholipid Syndrome

BACKGROUND: Anti-phospholipid antibody syndrome (APS) is an autoimmune thrombophilic syndrome characterized by venous and arterial thromboembolic disease (TED) in the presence of anti-phospholipid antibodies. Treatment requires anticoagulation, though the optimal choice for anticoagulant is not clear. Warfarin is the most common agent these patients are started on but it requires frequent INR monitoring and has many drug and dietary restrictions. The use of direct oral anticoagulants (DOACs) in this setting is an attractive option but has not been well studied. DOACS include apixaban, dabigatran, edoxaban, and rivaroxaban and have been approved in the treatment of venous thromboembolism but not in APS.METHODS: We sought to identify patients with antiphospholipid syndrome who have been treated with DOACs through a retrospective cohort analysis. Our objectives were to measure the incidence of recurrent TED, bleeding rates or other complications from the DOAC treatment. We used an institutional patient database at a single center to find patients on DOACs who were tested for antiphospholipid antibodies (lupus anticoagulant or Russell venom viper time, anti-cardiolipin antibody, and beta-2 glycoprotein-1 antibody) and fulfill the Revised Sapporo criteria regarding thrombosis, pregnancy complications, and laboratory evidence. Chart reviews were conducted to find bleeding and clotting complications, in addition to any other complications that led to changes in their management.RESULTS: Three hundred and sixty seven patients on DOACs were tested for antiphospholipid antibodies. One hundred and seventy of these had positive antiphospholipid testing. However, only 41 patients' positive tests were confirmed after a 12-week window per Sapporo diagnostic criteria. Most common DOAC used was rivaroxaban (29/41, 71%; see table 1). Within these 41 patients with confirmed APS, 5 (12%) had recurrent TED events (see table 1). Three of the patients who had recurrent TED were non-compliant with anticoagulation. These included 1 PE,1 DVT and 1 stroke patient. Two of those patients continued with a DOAC and did well since being compliant. The third patient had both thrombosis and hemorrhage of unclear etiology, so was not restarted on any anticoagulation. Two patients (5%) experienced major bleeding and 5 (12%) minor bleeding. Regarding the two major bleeds, one patient had a gastrointestinal bleed nearly 1 year after starting a DOAC and the second patient had a retroperitoneal bleed 2 months after starting. The second patient was treated with 4-factor activated prothrombin complex concentrate, which was complicated by a stroke. No patients died from any of the adverse events. Fourteen patients (34%) started on DOACs as the first line regimen while the rest had been previously treated with another anticoagulant. Reasons for switching to DOAC were mostly because of difficulty managing INR's with warfarin in 11 patients (27%). Thirty-two patients (78%) are still on a DOAC. For these 32 patients, safe and effective anticoagulation with a DOAC is noted for a median of 48 months (range 14-62 months).CONCLUSION: In this study, rates of recurrent TED and bleeding complications were shown to be similar to previously published studies using warfarin in APS. DOACs appear to be a safe and effective treatment option for APS. However larger prospective studies are needed for DOACs to be routinely considered. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.