Current status and value of testing antiphospholipid antibody in patients with acute ischemic stroke: a retrospective single-center study in China.

BACKGROUND AND PURPOSE: Testing for antiphospholipid antibodies (aPL) is useful to determine the cause of ischemic stroke in young and female patients. However, the clinical relevance of aPL in older patients with ischemic stroke remains unclear. We aimed to explore the status and diagnostic value of initial aPL testing in all patients with acute ischemic stroke. METHODS: We retrospectively analyzed patients with acute ischemic stroke who were consecutively hospitalized in our hospital between June 2012 and January 2022 and investigated the factors associated with performing aPL screening in real-world clinical practice. Furthermore, factors associated with initial aPL positivity were evaluated by comparing the demographic, etiological, and therapeutic characteristics. RESULTS: Of 1209 patients, 287 (23.7%) were tested for aPL and 58 (20.2%) tested positive. Physicians tended to conduct aPL testing on female patients (P<0.001), younger patients (P<0.001), patients with fewer vascular risk factors (P<0.001), and multiple infarctions in the multivascular blood supply area (P<0.001). Multivariate logistic regression analysis showed that only stroke of other determined etiology type was a significant influencing factor for positive aPL results (OR 2.97, 95% CI 1.137, 7.774, P=0.026), adjusting for sex, age, and causes of stroke, etc. CONCLUSION: Approximately one-quarter of the patients with acute ischemic stroke were tested for aPL. Age, sex, number of vascular risk factors, and neuroimaging features affected the discretion in performing aPL testing. aPL testing may be appropriate in older patients with no identified cause of ischemic stroke and may provide additional diagnostic opportunities for acute ischemic stroke.

Antiphospholipid Syndrome and Kidney Involvement.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the development of autoantibodies and the impairment of the coagulation system. Knowledge about this syndrome is increasing over time, but kidney involvement, especially APS nephropathy, still represents a challenge for physicians. SUMMARY: A "two hit" model has been hypothesized to explain APS pathophysiology, and the role played by some factors, such as the complement system, is becoming more and more clear. From a clinical point of view, along with thrombosis in any site and/or obstetric morbidities, that are the hallmarks of APS, a constellation of several other clinical symptoms is related to APS. These symptoms alone are not sufficient to fulfill Sydney criteria for APS and this could potentially lead to omitting some diagnoses. The mainstay of management of APS is antithrombotic therapy, but there are expectations for new drugs that regulate the immune system. APS could affect the kidneys in many ways and among them, APS nephropathy is an intriguing entity that has been overlooked in recent years. Novel studies on APS nephropathy are lacking. KEY MESSAGES: In this review, we discuss what we currently know about APS and its relationship with the kidney, with an eye toward the future perspectives. Multicenter studies on APS nephropathy are necessary in order to develop targeted therapies.

A review of the development of gangrene in patients with systemic lupus erythematosus - A 44-year follow-up study.

OBJECTIVES: This review addresses the question of what happens long-term to those systemic lupus erythematosus (SLE) patients who develop gangrene. It also seeks to find common clinical and serological features, risk factors and triggers and how best to manage this challenging complication. METHODS: We reviewed 850 patients with SLE attending a UK tertiary referral center, followed up over 44 years, assessing their demographics, clinical and serological features, treatment in the acute phase, their long-term outcome and long-term management. RESULTS: Ten out of 850 patients (1.2%) developed gangrene; the mean age of onset was 17 years (range 12-26 years) Eight out of 10 patients had a single episode of gangrene. One of the other two was not willing to have anticoagulation. The first episode of gangrene ranged from presentation to 32 years after SLE onset, mean duration of SLE at the onset of the gangrene was 18.5 years SD 11.5 years. Anti-phospholipid (PL) antibodies were over-represented in the patients with gangrene. All had active SLE at the time the gangrene developed. All patients were treated with intravenous (IV) iloprost infusions, and the antiphospholipid-antibody positive patients were anti-coagulated, most staying on long term anticoagulation. Underlying possible triggers were treated appropriately. Two patients who did not respond to the initial treatment needed further immunosuppression. All patients suffered digit loss. CONCLUSION: Although rare, gangrene is a sinister, potentially late developing complication of SLE, it rarely recurs. It is associated with anti-phospholipid antibodies, active disease, and other possible triggers such as infection and cancer. Anticoagulation therapy, steroids and iloprost, and further immunosuppression may be needed to stop the evolution of gangrene.

[Venous thromboembolism and antiphospholipid syndrome - considerations on diagnosis and treatment]. / Veneuze trombo-embolie bij antifosfolipidensyndroom.

Antiphospholipid syndrome (APS) is an auto-immune syndrome defined by thrombosis and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies. Antiphospholipid antibodies are a group of antibodies predominantly directed at phospholipid-bound plasma proteins. The more antibodies a patient has the higher the risk of thrombosis. The origin of the antibodies and the precise prothrombotic mechanism are incompletely understood. A diagnosis of APS can in certain clinical scenarios implicate a longer treatment with anticoagulants after a venous thromboembolism. High level evidence is absent. In addition, APS patients with a high risk antibody profile had a higher risk of arterial thrombosis in randomized trials when treated with direct oral anticoagulants compared to vitamin K antagonists. The number needed to screen in light of these possible consequences of an APS diagnosis for treatment, appears to high to justify routine screening. In this review we suggest indications for APS testing in the context of venous thromboembolism.

What you need to know about migraine in Hughes syndrome patients.

BACKGROUND: Headache, often migrainous, is common in patients with antiphospholipid antibodies, whether or not they meet Sydney criteria for a definite diagnosis of Hughes syndrome. Migraine may be a harbinger of stroke in this patient population and even refractory migraine may be highly responsive to antithrombotic therapy in this clinical context. PURPOSE: To summarize what is known to date about managing this important manifestation of the immune-mediated hypercoagulable Hughes syndrome. RESULTS: We provide a suggested management algorithm for refractory headache in this unique patient population. CONCLUSION: Most neurologists don't see or recognize many aPL-positive patients in their practice, so hematologists and rheumatologists who see these patients should recognize that refractory headache may be a manifestation of their immune-mediated hypercoagulable disorder and understand that the potential risks of not addressing this issue may be high.

Pregnancy in patients with systemic lupus erythematosus: a systematic review.

Systemic lupus erythematosus (SLE)-a most common disorder in women of reproductive age-has been described to be associated with adverse pregnancy outcomes. Despite the increased health risks for the mother (preeclampsia, lupus flare, arterial hypertension, gestational diabetes mellitus and thrombotic risk when antiphospholipid antibodies are present) and fetus (miscarriage, stillbirth, premature birth, intrauterine growth restriction and neonatal lupus), the majority of patients can deliver healthy neonates. With appropriate management by a multidisciplinary team, composing rheumatologists, obstetricians and neonatologists, women with SLE can achieve better pregnancy outcomes by monitoring associated predictive indicators, raising major concern for severe complications and somewhat early delivery if necessary. In this review, we summarize the latest advances in secondary infertility and pregnancy-related risk perception for lupus patients, with an emphasis on the safety of biological agents (mainly belimumab and rituximab) and traditional therapeutic regimens.

Antiphospholipid syndrome, antiphospholipid antibodies, and stroke.

Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease with heterogeneous clinicopathological manifestations and is a well-established cause of acute ischemic stroke (AIS) and transient ischemic attack (TIA), particularly in younger patients. There is growing recognition of a wider spectrum of APS-associated cerebrovascular lesions, including white matter hyperintensities, cortical atrophy, and infarcts, which may have clinically important neurocognitive sequalae. Diagnosis of APS-associated AIS/TIA requires expert review of clinical and laboratory information. Management poses challenges, given the potential for substantial morbidity and recurrent thrombosis, additional risk conferred by conventional cardiovascular risk factors, and limited evidence base regarding optimal antithrombotic therapy for secondary prevention. In this review, we summarize key features of APS-associated cerebrovascular disorders, with focus on clinical and laboratory aspects of diagnostic evaluation. The current status of prognostic markers is considered. We review the evidence base for antithrombotic treatment in APS-associated stroke and discuss uncertainties, including the optimal intensity of anticoagulation and efficacy of direct oral anticoagulants. Clinical practice recommendations are provided, covering antithrombotic treatment, supportive management, and options for anticoagulant-refractory cases, and we highlight the benefits of adopting a considered, multidisciplinary team approach.

Acute Coronary Syndromes in Antiphospholipid Syndrome-above Suspicion: A Systematic Review.

Antiphospholipid syndrome(APS) is an autoimmune disorder characterized clinically by vascular thrombosis and/or pregnancy morbidity, associated with persistently elevated titers of antiphospholipid antibodies on at least two measurements over 12 weeks apart. In this study, we conducted a systematic review of the literature utilizing the Pubmed platform, in order to acquire clinical information about acute coronary syndromes in patients with APS. The obtained articles were reviewed in order to register the clinical characteristics, the rate of occurrence, the prognosis and the therapeutic approach of these patients. APS should be considered in young patients with acute myocardial infarction, even in patients with normal coronary arteries. The pharmaceutical approach is mainly based on the vitamin K antagonists, and in certain occasions aspirin, without any definite guidelines on the subject. Further randomized clinical trials are imperative for a better understanding of the particular characteristics of this group of patients, so that a more complete therapeutic approach to be obtained.

[Efficacy of rituximab in minimal change disease, an atypical renal manifestation of antiphospholipid syndrome]. / Skutecznosc rytuksymabu w leczeniu choroby zmian minimalnych stanowiacej nietypowa nerkowa manifestacje zespolu antyfosfolipidowego.

Antiphospholipid syndrome (APS) is defined as presence of antiphospholipid antibodies along with hypercoagulable events. Renal involvement in APS usually manifests as thromboembolic complications observed in large blood vessels or small intrarenal vessels (APS nephropathy). We report a rare case of glomerulitis associated with APS and being characterised by features different from typical APS nephropathy. A CASE REPORT: A 23-years-old patient was admitted to the nephrology department with steroid-sensitive, steroid-dependent nephrotic syndrome secondary to minimal change disease, first diagnosed at the age of 18 months. Subsequent thromboembolic events, such as deep vein thrombosis, unilateral thrombosis of the popliteal artery, and pulmonary embolism, led to the diagnosis of antiphospholipid syndrome. The patient also had a history of acute kidney injury. On the day of admission, the patient had normal renal function and was taking an increased dose of prednisone owing to nephrotic syndrome relapse. In the past, attempts to reduce the dosage of glucocorticoids were made using cyclophosphamide, cyclosporin A, mofetil mycophenolate, and their combinations. It rendered ineffective as nephrotic syndrome relapses occurred. The patient's eligibility for the rituximab treatment was established in a series of diagnostic tests which excluded any contraindications. No adverse effects were observed during or after intravenous infusion of the drug. CONCLUSIONS: The case emphasizes a rare renal clinical manifestation of APS in nephrologist's practice. The combination of anti-CD20 monoclonal antibody and anticoagulants is highly likely to be the optimal solution for this problem.

Emerging Therapies in Antiphospholipid Syndrome.

The antiphospholipid syndrome (APS) is the most common cause of acquired immune-mediated thrombophilia. This syndrome is broadly defined by the presence of arterial or venous thrombosis, or pregnancy morbidity, in the presence of high levels of antiphospholipid antibodies. Despite recognition of this disorder more than 50 years ago, a fundamental unifying pathogenesis has not been determined. Due to this, mechanism-based therapies for APS are not available, and current management following thrombotic events suggests anticoagulation of indeterminate duration, or for obstetric complications, heparin/low molecular weight heparin and aspirin. However, APS is an autoimmune disorder, and several approaches focused on modulating the immune response or its effectors have been employed. Those which have been most extensively studied include hydroxychloroquine, rituximab and eculizumab, an inhibitor of complement C5. In this report, we review in depth, and critique, key clinical studies of these agents. Since all of these studies are small, our conclusions are qualified. However, it appears that hydroxychloroquine may enhance the anticoagulant efficacy of vitamin K antagonists in APS patients, and that rituximab may ameliorate some of the "non-criteria" manifestations of APS. The catastrophic antiphospholipid syndrome (CAPS) is associated with diffuse thrombosis, multi-organ dysfunction, and ∼30% mortality. A high incidence of complement regulatory gene mutations, and compelling data concerning the efficacy of eculizumab in CAPS, suggests an important role for complement in this disorder. However, additional work is needed to clarify the role of complement in non-catastrophic APS, though emerging data suggests that complement inhibition may be effective in preventing thrombosis in these patients as well.

The use of fondaparinux and rituximab for recurrent thrombotic events in antiphospholipid syndrome.

Limited evidence exists to guide the management of recurrent thrombosis occurring despite therapeutic anticoagulation in patients with thrombotic antiphospholipid syndrome (APS). In this case series, fondaparinux, with or without an antiplatelet agent, provided an effective and safe option in three patients with thrombotic APS, all two triple and one single positive for antiphospholipid antibodies, who had recurrent venous and/or arterial thromboembolism. Rituximab was also used in all patients. Recurrent events occurred despite therapeutic anticoagulation, including at high-intensity, with warfarin and subsequent low-molecular-weight heparin. There were no major bleeding events. Adjunctive therapies used for thrombosis included catheter-directed thrombolysis and rituximab.

Immunological parameters of recurrent miscarriages among women in Thi-Qar province.

Recurrent miscarriage (RM) is defined as the loss of pregnancy three or more consecutive times in the first and second trimester, which in some cases occurs due to immune abnormalities. This study aimed to assess some immunological parameters in women with recurrent miscarriages, including the level of antiphospholipid antibody (APA), anticardiolipin (ACA), antinuclear antibody (ANA), complement C3 and C4, and interleukine-3 (IL-3). We included 100 patients together with 100 healthy women as a control. ELIZA was used to measure some types of autoantibodies. APA and ACA significantly increased (P≤0.05) in patients compared to control. In addition, 29% of the patients were positive for antinuclear antibodies (ANA), while the control subjects had negative results for these autoantibodies. Regarding the complement, the serum levels of C3 and C4 were significantly elevated in the serum level of patients when compared to the control group, but in treated patients (heparin and low-dose aspirin), the levels of the complement (C3 and C4) showed a significant decrease in patients compared to total controls. Cytokine level (IL-3) significantly decreased in untreated patients 302.78 pg/ml compared to treated patients (741.57 pg/ml). Antiphospholipid antibodies are more prevalent among women with recurrent miscarriages and are also believed to be the result of abnormal autoimmune activation.

Treatment advances in antiphospholipid syndrome: 2022 update.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy morbidity, or non-thrombotic manifestations in patients with persistently positive antiphospholipid antibodies (aPL). Conventional treatment strategies of antiphospholipid syndrome focuses on antithrombotic agents, however they are usually not effective for microvascular and non-thrombotic manifestations of aPL. In parallel to our increased understanding of the mechanisms of aPL-mediated clinical events, immunosuppression has been increasingly used in aPL-positive patients. This review focuses on the role of potential targeted immunosuppressive treatments in APS (B-cell inhibition, complement inhibition, mechanistic target of rapamycin inhibition, and traditional rheumatologic disease-modifying agents including hydroxychloroquine) and future perspectives.

Idiopathic multicentric Castleman disease with positive antiphospholipid antibody: atypical and undiagnosed autoimmune disease?

Idiopathic multicentric Castleman disease (iMCD) is a systemic disorder characterized by systemic inflammation and organ dysfunction associated with an increase in pro-inflammatory cytokines. Some patients with iMCD are positive for autoantibodies, although their significance and relationship with specific associated autoimmune diseases are unclear. This study retrospectively analyzed the clinicopathological features of iMCD patients focusing on autoantibodies. Among 63 iMCD patients in our database, 19 were positive for at least one autoantibody. Among the 19, we identified five with plasma cell type (PC)-iMCD lymph node histopathology and positive anti-phospholipid antibodies. These patients were likely to have thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, organomegaly (TAFRO) symptoms, and thrombotic events. The present study suggests that patients with undiagnosed or atypical autoimmune diseases, including anti-phospholipid syndrome (APS), were treated for iMCD. APS may present with thrombocytopenia or even multi-organ failure, which overlap with clinical presentations of iMCD. Due to differences in the treatment regimen and follow-up, recognition of the undiagnosed autoimmune disease process in those suspected of iMCD is essential. Our study highlights the importance of complete exclusion of differential diagnoses in patients with iMCD in their diagnostic workup.

APA scoring system: a novel predictive model based on risk factors of pregnancy loss for recurrent spontaneous abortion patients.

The aim of this study was to analyse the risk factors of pregnancy loss of patients with recurrent spontaneous abortion (RSA) and develop a scoring system to predict RSA. Clinical data of 242 cases, with RSA who were treated at Fujian Provincial Maternity and Children's Hospital, were selected. The factors of pregnancy loss for RSA patients were evaluated by univariate and multivariate analyses. There were 242 RSA patients, of whom 34 (14.0%) developed pregnancy loss. A multivariate analysis showed the following adverse risk factors for RSA: antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies. The pregnancy loss rates of antinuclear antibody spectrum group, protein S deficiency group and antiphospholipid antibodies group were 25.0%, 22.5% and 19.4%, respectively. Each of these factors contributed 1 point to the risk score. The pregnancy loss rates were 6.3%, 24.6%, 50% for the low-, intermediate- and high-risk categories, respectively (p < .001). The area under the receiver operating characteristic curve for the score of RSA was .733. Our findings suggest that this validated and simple scoring system could accurately predict the risk of pregnancy loss of RSA patients. The score might be helpful in the selection of risk-adapted interventions to decrease the incidence. Impact StatementWhat is already known on this subject? The live birth rate increases to 80%-90% after anticoagulant and/or immunosuppressive treatment in patients with RSA. However, there is still a high rate of re-abortion even after active treatment.What do the results of this study add? Antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies were independent risk factors for pregnancy loss. A novel predictive model based on these factors was then established and validated.What are the implications of these findings for clinical practice and/or further research? The newly developed score might be helpful in the selection of risk-adapted interventions to decrease the incidence. For patients in the intermediate-risk and high-risk groups, we should conduct more targeted studies and formulate corresponding therapies to improve the success rate of treatment.

Obstetric anti-phospholipid syndrome: from pathogenesis to treatment.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by clinical manifestations such as thrombosis and obstetric complications with documented persistence of antiphospholipid antibodies (aPLs). Recent studies have revealed that the cause of aPL-related obstetric complications is dysfunction of placental trophoblasts and inflammation of the maternal-fetal interface induced by aPLs, not thrombosis. Although aPLs are associated with recurrence of serious complications during pregnancy, appropriate combination therapy with heparin and low-dose aspirin can improve the course of 70-80% of subsequent pregnancies. Preconception counseling and patient-tailored treatment are fundamental to improving maternal and fetal outcomes. Non-anticoagulant treatments such as hydroxychloroquine and statins are being developed for cases refractory to conventional treatment. Risk factors for thrombosis after pregnancy complications were identified based on the analysis of large databases of obstetric APS.

The digestive system involvement of antiphospholipid syndrome: pathophysiology, clinical characteristics, and treatment strategies.

Antiphospholipid syndrome (APS) is an autoimmune disease mainly characterised by vascular thrombosis and pregnancy morbidity. APS has broad spectrum of clinical manifestations. The digestive system involvement of antiphospholipid syndrome is a critical but under-recognised condition. Digestive system involvement may be the result of direct (autoimmune-mediated) or indirect (thrombotic) mechanisms. Liver is the most commonly involved organ, followed by intestines, oesophagus, stomach, pancreas and spleen. This review describes possible digestive system manifestations in APS patients, and illustrates the epidemiology and possible pathophysiology of APS. The role of different treatment strategies in the management of digestive system manifestations of APS were also discussed.Key messagesAntiphospholipid syndrome is a multi-organ, multi-system disease and its clinical manifestation spectrum is gradually expanding. Since the first diagnosis of APS, the clinical manifestations of digestive system have been reported successively. This narrative review describes the major digestive system manifestations of APS and illustrates the epidemiology, pathophysiology and the role of therapeutic strategies of these patients.

Pregnancy Outcomes in Systemic Lupus Erythematosus Women: A single tertiary centre experience.

OBJECTIVES: This study was conducted to assess pregnancy outcomes in women with systemic lupus erythematosus (SLE) in Oman. METHODS: A retrospective cohort study of 149 pregnancies in 98 women with SLE was conducted over 10 years to evaluate the impact of clinical and laboratory parameters in predicting adverse pregnancy outcomes. RESULTS: Mean maternal age was 30.6 ± 5 years ranging from 20-44 years, and the mean disease duration was 10 ± 5 years, ranging from 2-27 years. The most common maternal manifestations were joint pain in 36 (24.2%), lupus nephritis (LN) in 18 (12.08%), preeclampsia in 11 (7.4%), eclampsia in three (2%) and lupus flare in one pregnancy. The live birth rate was 139 (93.3%) with a mean gestational age of 36 ± 2 weeks ranging from 26-40 weeks. In total, 55 (39.6%) were preterm deliveries, six (4%) pregnancies ended in miscarriage, and four (2.7%) resulted in intrauterine fetal death. Intrauterine growth restriction was observed in 49 babies (35%). A significant association was found between hypertension (HTN) and miscarriage (P = 0.024) and preterm birth (P = 0.019). In addition, HTN was positively associated with preeclampsia (P = 0.004) and LN (P = 0.048). Antiphospholipid syndrome impacted preterm birth (P = 0.013) and postpartem haemorrhage (PPH) (P = 0.027) and was found to be a significant predictor for women developing deep vein thrombosis and pulmonary embolism (P <0.001 for both). CONCLUSION: Despite potential complications, most pregnancies complicated by SLE in Oman result in good outcomes. Adverse pregnancy outcomes, however, may still occur in women with SLE. In women with SLE, pregnancy planning, careful antenatal monitoring and efficient SLE treatment need to be undertaken for successful pregnancy outcomes.

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends.

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.

16th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome.

Obstetric antiphospholipid syndrome (APS) remains a clinical challenge for practitioners, with several controversial points that have not been answered so far. This Obstetric APS Task Force met on the 16th International Congress on Antiphospholipid Antibodies in Manchester, England, to discuss about treatment, diagnostic and clinical aspects of the disease. This report will address evidence-based medicine related to obstetric APS, including limitations on our current management, the relationship between antibodies against domain 1 of ß2GPI and obstetric morbidity, hydroxychloroquine use in patients with obstetric APS and factors associated with thrombosis after obstetric APS. Finally, future directions for better understanding this complex condition are also reported by the Task Force coordinators.