Positive Antiphospholipid Antibodies Research Articles

A retrospective study of the prevalence of isolated prolongation of activated partial thromboplastin time in the preoperative setting

BackgroundIsolated prolongation of activated partial thromboplastin time (APTT) has various causes including inheritable bleeding disorders, and has medical significance as it can lead to the cancelation of surgery. However, even an emergency surgery can be conducted in a patient presenting with severe APTT prolongation, provided careful evaluation and appropriate measures are taken. Hence, the identification of the underlying etiology of the prolonged APTT is crucial. To date, little evidence exists regarding the prevalence of isolated APTT prolongation in Japanese patients undergoing surgery. Herein, we aimed to clarify the prevalence of isolated prolongation of APTT in the preoperative setting and to identify the reasons underlying isolated, severely prolonged APTT.MethodsPreoperative coagulation data of all elective and emergent patients who presented to the anesthetic department between January 1, 2020, and June 30, 2023, were retrospectively collected. Isolated prolongation of APTT was defined as an APTT ≥ 37 s with an international normalized ratio of prothrombin time < 1.2. The underlying etiology of the patient with isolated, severely prolonged APTT (≥ 46 s) was investigated, and canceled surgical procedures in relation to the isolated APTT prolongation were searched.ResultsOverall, 10,684 measurements from 9413 patients were included, of which 725 (6.8%) were identified as having isolated APTT prolongation. The reasons for the severely prolonged APTT (n = 60) were miscellaneous, with the most frequently detected etiology being antiphospholipid antibody positivity. Preoperative isolated APTT prolongation contributed to the cancellation of surgery in elective five cases.ConclusionsWe clarified the prevalence of preoperative isolated prolongation of APTT. The presence of antiphospholipid antibody was the most frequently detected etiology of the patient with isolated, severely prolonged APTT. The present study provides an important dataset regarding the isolated prolongation of APTT in East Asian patients undergoing surgery.

Clinical Features and Outcomes of Twin Pregnancies with Antiphospholipid Antibodies Positivity: A Retrospective Study.

This study aimed to evaluate the impact of twin pregnancies with antiphospholipid antibody (aPL) positivity, a rare and complex clinical condition that remains a huge challenge for management. This study enrolled twin-pregnant women at our hospital between January 2018 and August 2023. Women with and without aPL positivity were selected using propensity score matching (PSM). Clinical features and pregnancy outcomes were compared between the two groups in the PSM cohort. To analyze the effect of aPL positivity on pregnancy outcomes, multivariate logistic models were used to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI). Among the 773 women with twin pregnancies, aPL positivity was found in 26 women (3.36%). In the PSM cohort, there were 24 twin-pregnant women with positive aPL, and 48 women without aPL were selected as controls. Twin-pregnant women with aPL positivity had a higher proportion of abortion (8.33% vs 0, P = 0.043), preterm birth < 34 weeks (33.33% vs 8.33%, P = 0.007) and very low birthweight (<1500 g) (20.83% vs 4.17%, P = 0.016) than the control group. In addition, stillbirth of one fetus was observed in one twin-pregnant woman with positive aPL. Multivariate logistic regression analysis revealed that twin pregnancy with aPL positivity was associated with preterm birth < 34 weeks (aOR = 2.76, 95% CI: 0.83-4.70, P = 0.005), very low birthweight (<1500 g) (OR = 2.40, 95% CI: 0.18-4.67, P = 0.034) and small for gestational age (SGA) (aOR = 1.66, 95% CI: 0.22-3.10, P =0.024). Twin pregnancies with aPL positivity were correlated with obstetric complications, including abortion, preterm birth < 34 weeks and very low birthweight (<1500 g). The detection of aPL may be of clinical significance for women with twin pregnancies and should be considered in future studies.

Dilemmas in the diagnosis and management of antiphospholipid syndrome

Antiphospholipid syndrome (APS) is characterized by thrombosis (which may be venous, arterial, or microvascular) and/or pregnancy morbidity in association with persistently positive antiphospholipid antibodies. Although thrombosis and pregnancy morbidity are the main clinical criteria for a diagnosis of APS in the revised Sapporo (Sydney) criteria, recently published American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for APS have significantly refined the diagnostic algorithm to include a scoring system clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular thrombosis, obstetric, cardiac valve, and hematologic). Diagnosis of APS is complicated by the fact that significant heterogeneity exists in patients’ clinical presentation, underlying vascular risk factors, and methods of detecting antiphospholipid antibodies. Despite the autoimmune nature of APS, anticoagulation remains the main strategy for secondary prevention of thrombosis. However, optimal antithrombotic treatment in APS patients with arterial thrombosis remains controversial due to a paucity of data from randomized controlled studies. In this paper, we present 2 cases and highlight the diagnostic and therapeutic challenges they pose and how we approach them in the light of current evidence.

P030 Multiple autoantibody formation post COVID-19 infection

Abstract Background/Aims COVID-19 has been linked to the formation of a number of autoantibodies. This case is an important reminder to clinicians interpreting autoantibody results in conjunction with clinical manifestations. A previously fit 51 year old gentleman, with no prior history of autoimmune disease required admission with respiratory symptoms in April 2020 consistent with COVID-19 infection. His acute respiratory illness was complicated by empyema and left-sided pneumothorax requiring left pleural decortication and adhesiolysis under (VATS). Persistent respiratory symptoms and fatigue lead to investigations for long COVID. Positive antibodies detected were dsDNA 166IU/ml, Proteinase 3 antibodies 20IU/ml, Myeloperoxidase antibodies 32IU/ml, IgG anticardiolipin antibodies 90IU/ml and Glomerular basement membrane antibodies 351 IU/ml. Negative autoantibodies included ANA, RF, aCCP, b2GPI, smooth muscle, AMA and myositis related antibodies. Methods There were no clinical signs or symptoms of inflammatory arthropathy, vasculitis, thrombosis or connective tissue disease. Other investigations included a CT thorax showing no new lung lesions, unremarkable urine dipstick, normal urine ACR, normal US abdomen, CT sinuses and MRI brain. Results Trial course of prednisolone was given therapeutically due to long COVID symptoms. There was no significant impact on symptoms/ autoantibody titres thus steroids were discontinued. The patient was followed closely by the rheumatology team for two years. During that time, the autoantibody levels gradually decreased, and he did not develop clinical signs of autoimmune disease. His long COVID symptoms persisted, and he remains under the long COVID clinical team. Conclusion COVID-19 infection is known to cause an immune response. There have been published cases of positive ANA, U1-snRNP anti-SS-B/La, ANCA, anti-phospholipid and anti-SRP antibody formation following COVID-19 infection. The link between the pathophysiology of COVID-19, autoantibody formation and the role of autoimmunity is still unclear. This man's case was unusual in the number and variety of autoantibodies formed post COVID, this has not been reported in the literature to date. Some of the autoantibodies detected are highly specific for certain conditions, for example anti-GBM antibodies have a high specificity for Goodpasture’s syndrome, thus this case also illustrates the need to interpret positive autoantibodies in the context of clinical findings and history. Disclosure S. Islam: None. N. Erb: None.

Leg Ulcers in a Patient With Systemic Lupus Erythematosus and Successful Treatment With Anticoagulant Therapy.

Among specific skin manifestations of systemic lupus erythematosus such as leukocytoclastic vasculitis, and vasculopathy, the development of leg ulcers is rare and frequently seen in patients with antiphospholipid antibody positivity. Here we report the rapid healing of a leg ulcer without antiphospholipid antibody positivity in a patient with lupus in response to anticoagulant therapy. As in our case, when immunosuppressive agents are inadequate in lupus patients who develop leg ulcers, it may be beneficial to support the treatment with anticoagulants.

Noncriteria antiphospholipid antibodies in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant, anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several noncriteria aPL have been identified. Some noncriteria aPL are well studied, such as IgA aCL and aβ2GPI, the antiphosphatidylserine-prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2-glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other noncriteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin-cardiolipin complex, anti-protein S/protein C. Measurement of some of these noncriteria aPL (aPS/PT, aDI) is useful in the laboratory work-out of APS in specific situations. We have to differentiate between patients who are positive for noncriteria aPL only, and patients who have both criteria and noncriteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on noncriteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified.

Laboratory assessment of antiphospholipid syndrome: Laboratory data.

Thorough assessment of the antiphospholipid syndrome (APS) includes retesting of positive antiphospholipid antibody (aPL) tests after at least 12 weeks, and a full antiphospholipid antibody profile. To what extent this work-up is done in clinical practice is unknown. Data on 25 116 in- and out-hospital patients tested for the presence of lupus anticoagulant (LA), the aPL which most strongly correlates with thrombosis, was extracted from the laboratory information system of the only laboratory that performs LA tests in the Capital Region, Denmark. We estimated fraction of repeated tests, tests repeated within the recommended time span, and fraction with a full aPL profile. Out of 25 116 patients, 843 were positive for LA (3.3%), and 3948 results were inconclusive (16%). Only 51% (95% CI of the proportion: 48%-54%) (n = 431) of positive tests were repeated. The proportion of inconclusive LA test results increased from 13% (12%-15%) in 2009 to 20% (19%-22%) in 2020. Out of the positive tests repeated within the first year, only 60/353 (17%; 13%-21%) were repeated within 12-16 weeks; 177/353 (50%; 45%-55%) were re-tested within the first 12 weeks of first positive test result. The proportion of patients with a full antiphospholipid antibody profile increased from 161/1978 (8%) in 2010 to 1041/1978 (43%) in 2020. We found several issues with the laboratory workup of APS. This indicates a need for increased awareness of comprehensive laboratory assessment of possible APS as well as a closer collaboration between the laboratory and clinicians.

Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy

BackgroundLymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.MethodsRepeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren’s syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β2 glycoprotein I [β2GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.ResultsWomen with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4 + T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4 + T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4 + T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4 + T cell count was unrelated to treatment.ConclusionLymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.

Retinal Vasculitis in a Patient with Hansen's Disease.

Hansen's disease is endemic in over 140 countries worldwide and a potentially blinding condition. We describe a case of retinal vasculitis in a patient with Hansen's disease with concomitant positive antiphospholipid antibody serology, a potentially under-reported complication in this setting. A 37-year-old Brazilian man systemically stable on triple therapy (clofazimine, rifampin, dapsone) for Hansen's disease presented for a comprehensive ophthalmic evaluation. Dilated exam revealed diffuse peripheral intraretinal hemorrhages in his right eye. Fluorescein angiography showed peripheral non-perfusion, abnormal shunt vessels and leakage from the retinal veins in the right eye and peripheral non-perfusion and vascular leakage in the fellow eye, consistent with vasculitis. Laboratory workup was notable for positive antiphospholipid antibodies (lupus anticoagulant, anticardiolipin IgM, anti-beta-2 glycoprotein 1 IgM) and normocytic anemia. As antiphospholipid antibodies are present in a large proportion of patients with Hansen's disease, it is possible that retinal vasculitis may be more common than previously thought. The extent to which retinal vasculitis occurs in Hansen's disease remains uncertain and possibly underestimated due to the frequency of anterior segment scarring, which impedes retinal evaluation. Heightened surveillance for potential retinal vascular complications is warranted.

Contraception for antiphospholipid syndrome and systemic lupus erythematosus (according to the recommendations of the European Alliance of Associations for Rheumatology/American College of Rheumatology, EULAR/ACR)

Maintaining and strengthening the health of the population is one of the primary functions of society. Inadequate understanding of the importance of contraception by the medical community and its application by society can lead to the population’s reproductive health becoming compromised. Basic knowledge of effective and safe contraceptive methods is important for every rheumatologist, as reproductive health affects both the general condition of patients and the course of the main rheumatic diseases (RH). This is particularly true for patients with antiphospholipid antibody (aPL) positivity, antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The presence of aPL/APS, as well as the activity of SLE, are the main factors determining the choice of contraceptive method and the risk of hormonal contraception in patients with RH. Meanwhile, the use of appropriate (highly effective and safe) contraceptive therapy in this category of patients allows not only to plan the birth of a child, but also to avoid unwanted pregnancy in cases of disease activity, the use of embryotoxic and teratogenic drugs, as well as to carry out optimal treatment of concomitant pathology, which the supervising rheumatologist should be well aware of. This publication is devoted to the consideration of the main issues of contraception in the most “vulnerable” category of patients with RH – with positive aPL, APS and SLE.

Recurrent miscarriage and low-titer antiphospholipid antibodies

ObjectiveTo evaluate the clinical features and pregnancy outcomes in patients experiencing recurrent miscarriage (RM) with either low-titer or medium-high titer positivity of antiphospholipid antibodies (aPL).MethodsA retrospective review of medical records was conducted for patients with aPL positivity and recurrent miscarriage between 2018 and 2022. The clinical features, treatment strategies, outcomes were compared between the patients with low (n = 92) and medium (n = 32) titer of aPL.ResultsA total of 118 patients, resulting in 124 obstetric episodes (pregnancies), with a mean age of 33. 15 ± 4.56 and 31.47 ± 4.41 years between the two groups. The low-titer group exhibited a higher frequency of anti-cardiolipin antibodies IgM (P < 0.001), whereas the medium-high titer group demonstrated a higher frequency of anti-β2-glycoprotein 1 antibodies IgG (P < 0.001) and IgM (P = 0.032). Moreover, the medium-high titer group displayed a significantly elevated erythrocyte sedimentation rate compared to the low-titer group (P < 0.05). In the low-titer group, 71 patients (77.2%) received appropriate treatment, resulting in 48 live births (67.6%) and 23 repeat abortions (32.4%). In the medium-high titer group, 29 patients (90.6%) received relevant treatment, leading to 23 live births (79.3%) and 6 repeat abortions (20.7%). No significant differences were observed in live births or maternal-fetal complications between the two groups (all P > 0.05).ConclusionNoteworthy distinctions in laboratory parameters were identified between the low-titer and medium-high titer groups. However, when appropriately treated, the fetal-maternal outcomes were comparable in both groups. Timely intervention by clinicians is imperative to enhance pregnancy outcomes in patients experiencing recurrent miscarriage with low levels of aPL.Key Points• This study challenges the conventional belief that only the higher antiphospholipid antibodies (aPL) titers directly correlated with worse pregnancy outcomes, which emphasized the importance of patients with low titer positive aPL-positive RM.• The results underscore the need for timely intervention in women with low titer aPL-positive RM, as it leads to favorable maternal–fetal outcomes.

Digital gangrene in systemic sclerosis patients: not only due to the microvascular disease.

This study aims to investigate the characteristics, risk factors, and outcomes of digital gangrenes in SSc patients, and to identify whether vasculitis is one of the causes for digital gangrene. A retrospective case-control study was performed from February 2003 to April 2021. Forty-three SSc patients with digital gangrene admitted to Peking Union Medical College Hospital were included. One-hundred forty-six age- and sex-matched SSc patients without gangrene were selected as controls during the same period. Univariate and multivariate logistic regression analysis was used to determine risk factors. Among 43 SSc patients with gangrene, 93.0% had Raynaud's phenomenon (RP) and 32.6% had current or previous digital ulcers (DU). SSc patients with digital gangrene had more ESR elevation (54.8% vs. 34.9%, p = 0.020) and higher level of high-sensitive C reactive protein (median 7.2mg/L vs. 1.8mg/L, p = 0.045) compared with controls. In the multivariable logistic regression analysis, smoking history (OR 4.119, p = 0.037), anti-centromere antibody positivity (OR 3.542, p = 0.016), anti-neutrophil cytoplasmic antibody positivity (OR 22.605, p = 0.037), and anti-phospholipid antibody positivity (OR 16.563, p = 0.001), as well as elevated ESR (OR 2.524, p = 0.038) were identified as independent risk factors for gangrenes. Most (79.1%) cases were treated with combination of immunosuppressive and vasodilating therapy, and four cases also got remised after treatment of only glucocorticoid and immunosuppressive agent. Smoking history; positive-ACA, ANCA, and anti-phospholipid antibodies; and increased ESR were independent risk factors for digital gangrenes in SSc. Vasculitis and macrovascular disease may contribute to the progression of digital gangrenes. Key Points •18.6% of SSc patients with digital gangrene had macrovascular stenosis. •Smoking, positive-ACA, ANCA, aPL, and increased ESR were indicators for digital gangrenes in SSc. •Vasculitis and macrovascular disease may involve in the pathogenesis.

Clinical presentation and outcomes in patients with antiphospholipid syndrome-associated adrenal hemorrhage. A multicenter cohort study and systematic literature review

BackgroundAdrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR). MethodsWe performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis. ResultsWe included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47–9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30–11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33–9.85). ConclusionAH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.

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

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

Association of anti-phospholipid antibodies and hepatitis B virus infection in Najaf Governorate

Abstract Background: Antiphospholipid syndrome (APS) is an autoimmune disease with multifactorial risk factors including genetic and environmental factors such as viral infection, and it can be diagnosed by the presence of antiphospholipid antibodies (APLA) in the serum. Hepatitis B virus (HBV) is one of the most prevalent viral infections in the world and has been connected to a number of autoimmune illnesses. Some studies suggested that HBV might be the cause of APLA production and APS development. No previous study was done in Iraq regarding the relationship between these two. Objective: To estimate the prevalence of APLA in HBV-infected individuals in Najaf. Materials and Methods: A cross-sectional study was done in Najaf from September 2022 to March 2023, and it included 113 patients (70 were males, age range was 15–85 years) with HBV infection and without any history of APS. They were tested for Hepatitis B core (HBc) total and immunoglobulin M (IgM) Abs and then tested for APLA by enzyme-linked immunosorbent assay (ELISA) technique. The Statistical Program for Social Sciences (SPSS) version 26.0 was used for statistical analysis. Results: Only four patients were positive for HBc total and IgM the remaining 109 were positive for IgG only, 38 (33.63%) were positive for APLA, and the age group (41–50 years) with the highest rate of APLA positivity. Non-significant statistical difference was seen between APLA and gender or age. Acute HBV had higher titers of APLA. Conclusion: HBV may lead to the production of APLA in some patients without any other risk factors, especially in middle-aged patients.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-β2-glycoprotein I(β2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and β2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.

Choroid plexus and perivascular space enlargement in neuropsychiatric systemic lupus erythematosus.

Choroid plexus (CP) enlargement is proposed as a marker of neuroinflammation in immune-mediated conditions. CP involvement has also been hypothesized in the immunopathology of systemic lupus erythematosus (SLE). We investigated whether CP enlargement occurs in SLE patients and its association with neuropsychiatric involvement. Additionally, we explored abnormalities along the glymphatic system in SLE patients through enlarged perivascular space (PVS) quantification. Clinical assessment and 3 Tesla brain dual-echo and T1-weighted MRI scans were obtained from 32 SLE patients and 32 sex and age-matched healthy controls (HC). CPs were manually segmented on 3D T1-weighted sequence and enlarged PVS (ePVS) were assessed through Potter's score. Compared to HC, SLE patients showed higher normalized CP volume (nCPV) (p = 0.023), with higher CP enlargement in neuropsychiatric SLE (NPSLE) (n = 12) vs. non-NPSLE (p = 0.027) patients. SLE patients with antiphospholipid antibodies (APA) positivity (n = 18) had higher nCPV compared to HC (p = 0.012), while APA negative ones did not. SLE patients also had higher Potter's score than HC (p < 0.001), with a tendency towards a higher number of basal ganglia ePVS in NPSLE vs. non-NPSLE patients. Using a random forest analysis, nCPV emerged as a significant predictor of NPSLE, together with T2-hyperintense white matter (WM) lesion volume (LV) and APA positivity (out-of-bag AUC 0.81). Our findings support the hypothesis of a role exerted by the CP in SLE physiopathology, especially in patients with neuropsychiatric involvement. The higher prevalence of ePVS in SLE patients, compared to HC, suggests the presence of glymphatic system impairment in this population.

Evaluation of the Efficacy and Safety during Treatment with TPO-Ras in 40 SLE-ITP and APS-ITP Patients

Objectives: Thrombopoietin receptor agonists (TPO-RAs) have emerged over the last decade as a therapeutic option in primary immune thrombocytopenia (ITP). TPO-RAs have demonstrated their efficacy in more than 70% of cases and are taking an increasingly important place in second line therapy. However, to date, no prospective cohort has been able to question the efficacy and safety of TPO-RAs in systemic lupus erythematosus (SLE-ITP) and antiphospholipid syndrome (APS-ITP) patients, particularly regarding venous and arterial thrombosis risks in this population. Methods: This multicenter retrospective cohort study was conducted from 2012 to 2023 in seven hospitals belonging to the French national network for adult ITP. We assessed the efficacy and the tolerance of TPO-RAs on a large retrospective cohort with a long follow-up of patients with ITP associated with 1) SLE or 2) primary or secondary APS or 3) with antinuclear antibodies (ANA) and anti-dsDNA or anti-Sm antibodies or 4) with ANA and at least one antiphospholipid antibody (APA) without thrombotic events (TEs). We studied the efficacy according the international criteria of response (Rodeghiero et al, Blood 2009) and the incidence of TEs, the risk factors for the occurrence of thrombosis, the management of TPO-RAs and their combination with antiplatelet agents or anticoagulants. Results: We included 40 ITP patients treated with TPO-RAs; 28 SLE-ITP, four APS-ITP, four with both SLE and APS, and four with significant ANA and APA positivity without definite SLE or APS. Five patients were triple positive for APA. The median duration of follow up was 46 months (1-132). The overall response rate was 84.2% for patients treated with romiplostim and 71% for those treated with eltrombopag after failure of standard treatments such as corticosteroids, intravenous immunoglobulins, rituximab and immunosuppressive agents. Eight TEs occurred in seven (17.5%) patients at a median of 119 days (IQR=171.5) after eltrombopag (n=4) or romiplostim (n=4) initiation with a median exposure duration of 37 days (13-119) for romiplostim and 255 days (30-807) for eltrombopag. Two venous TEs were observed including one cerebral vein thrombosis and one pulmonary embolism. We observed six arterial thrombotic events, such as myocardial infarctions and ischemic strokes including one fatal catastrophic APS. Four of these patients had a history of APS, and most had thrombotic risk factors and positive APA. TPO-RAs were continued after TEs in two patients for a total duration of 20 and 53 months in association with an antiplatelet agent for one patient and a combination of an antiplatelet agent and an anticoagulant for the second one without a new TE thereafter. TPO-RAs were transiently stopped and then reintroduced due to ITP flare in two patients. A new episode of myocardial infarction occurred in one of them despite association with antiplatelet agents requiring TPO-RAs definitive arrest. Conclusion: We confirmed the effectiveness of TPO-RAs in over 70% of SLE-ITP and APS-ITP patients who failed to respond to corticosteroids, intravenous immunoglobulins, rituximab and/or standard immunosuppressive agents. Nevertheless, these findings highlight the need to carefully consider the potential benefits and thrombotic risks before initiating TPO-RAs, especially in elderly patients with thrombotic risk factors and positive APA or a confirmed APS. Further studies are needed to evaluate more precisely the TEs risk factors of these agents in this specific population, in order to better select SLE and APS-ITP patients who could benefit from them.

Natural supplements in antiphospholipid syndrome: A case for further study

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or pregnancy complications in the presence of persistently positive antiphospholipid antibodies (aPL). Although long-term anticoagulation with vitamin K antagonists is considered standard of care, there is an unmet need for safe therapeutics as primary thromboprophylaxis or adjuncts to standard of care in APS. APS is driven by oxidative stress, procoagulant, proinflammatory and angiogenic pathways. For these reasons there has been an increased interest into the investigation of antithrombotic, anti-inflammatory and anti-oxidant properties of natural supplements in APS. The objective of this review is to summarize the mechanistic, epidemiologic and clinical evidence behind the use of natural supplements in APS, with a specific focus on vitamin D, omega-3 fatty acids, coenzyme Q10, gingerol, and isoquercetin. This review should serve as a compelling argument for the future study of natural supplements in APS.

Do Patients with Antiphospholipid Syndrome Have More Significant Venous Thromboembolic Clot Burden?: A Single-Center Retrospective Analysis

Background: Antiphospholipid syndrome (APS) is a prothrombotic condition defined by arterial or venous thrombotic events and/or obstetrical morbidity in the presence of persistently positive antiphospholipid antibodies (aPL). Venous thromboembolic disease (VTE), comprised mostly of deep vein thrombosis (DVT) and pulmonary embolism (PE), is the initial presenting clinical manifestation in approximately 35% of APS diagnoses. VTE is a heterogenous disease and can present with varying degrees of clot burden. Lower extremity DVT can present with thrombus in the iliofemoral, femoropopliteal, and/or distal calf veins; pulmonary embolism can present with thrombus in the main pulmonary arteries, lobar branches, segmental, and/or subsegmental branches. In both DVT and PE, more proximal clot burden portends higher morbidity and mortality. While VTE is a commonly encountered clinical presentation, the decision regarding whom to test for APS is often challenging. Current guidelines recommend that clinicians consider testing for APS in patients with unexplained venous or arterial thrombotic events, especially young patients, or when a patient has one or more specific adverse outcomes related to pregnancy. To date, no data exist to suggest that patients with APS are more likely to present with more extensive venous thromboembolic clot burden as compared to patients without APS. Purpose: To assess clot burden in patients with a co-diagnosis of VTE and APS in comparison to patients with VTE without APS to determine if clot burden should be considered when deciding whom to test for APS. Methods: This retrospective cohort study included adult patients with a history of VTE who had also been tested for APS within a multihospital academic healthcare system from December 1, 2019 through January 31, 2022. All patients in the study had a history of VTE and were considered to be positive for APS if they had persistently positive aPL and/or lupus anticoagulant in accordance with the revised Sapporo APS Classification Criteria. Patients were excluded if they had confounding provoking risk factors for thrombosis. Patients were stratified as APS and non-APS. Significant clot burden was defined as PE involving the main and/or lobar pulmonary arteries or DVT involving the iliofemoral veins. Assessment of clot burden was performed by review of radiology reports of the sentinel clotting event.Patients were further stratified based on age, BMI, insurance status, severity of APS (triple-positive APS versus non-triple-positive APS), and type of APS (primary versus secondary). Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Chi square test was used to compare percentages and t-test was used to compare means. Univariate and multivariate regression models were used to analyze the predictors of significant clot burden. Results: We identified 748 patients with a history of VTE who had also been tested for APS. The study population was comprised of 53.1% females with a median age of 59 (IQR 46-69). A majority of the patients were Caucasian (85%). APS was detected in 75 (10%) patients. Significant clot burden was present in 29 (38.7%) APS patients and 269 (40.0%) non-APS patients (OR 0.95, 95% CI 0.58-1.56; P = 0.85). On univariate analysis, age (OR 1.01, 95% CI 1.00-1.02; P = 0.02) and being uninsured (OR 9.2, 95% CI 1.10-76.10; P = 0.04) were associated with more significant clot burden. No predictors for significant clot burden were found on multivariable analysis. Triple positive APS (OR 0.83, 95% CI 0.16-4.21; P = 0.82) and primary APS (OR 0.72, 95% CI 0.15-3.45; P = 0.68) were not associated with more significant clot burden. Conclusions: In this retrospective cohort of 748 patients with a history of VTE, the presence of antiphospholipid syndrome was not associated with more significant VTE clot burden as compared to non-APS patients. Based on these data, VTE clot burden may not be a reliable predictor for the presence of APS. Study limitations include selection bias, retrospective design, and lack of precise volumetric measurement of blood clots.