Transcatheter mitral valve-in-valve for pregnancy with anti-phospholipid syndrome: a case report.

BACKGROUND: Perioperative management and cardiac surgery in pregnant women with anti-phospholipid syndrome combined with heart valve disease have been rarely reported. CASE PRESENTATION: We describe a case of transcatheter mitral valve-in-valve replacement in a pregnant woman with bioprosthetic valve failure and anti-phospholipid syndrome at 18 weeks' gestation. The patient underwent a cesarean section delivery at 34 weeks of gestation, resulting in the birth of a healthy baby. CONCLUSIONS: Transapical mitral valve-in-valve surgery resulted in safe maternal and infant outcomes in a pregnant woman with anti-phospholipid syndrome combined with mitral bioprosthetic valve failure. The success of this procedure underscored the importance of multidisciplinary teamwork.

Acute Q fever revealed by an anti-phospholipid syndrome: A case report.

INTRODUCTION: Q fever is a zoonosis caused by Coxiella burnetii. Acute infection is mainly asymptomatic. In other cases it mainly causes a flu-like illness, a pneumonia, or an hepatitis. We present an atypical case of an acute Q fever revealed by a massive pleural effusion. CASE REPORT: We report the case of a 43-year-old man referred to our hospital for an acute respiratory distress. Further analyses showed an exudative eosinophilic pleural effusion, associated with a pulmonary embolism and a deep femoral vein thrombosis. Aetiologic explorations revealed an acute Q fever (IgM and IgG against C. burnetii phase II antigens) associated with anti-phospholipids. The outcome was favorable with vitamin K antagonists, doxycycline, and hydroxychloroquine, till the negativation of the anti-phospholipid antibodies. DISCUSSION AND CONCLUSION: During acute C. burnetii infections, anti-phospholipid antibodies are highly prevalent but thrombotic complications are rare. The 2023 ACR/EULAR APS criteria restricts the diagnosis of APS, as in our case of acute severe infection. In front of an atypical pneumonia and/or thrombotic events, screening of C. burnetii and anti-phospholipid antibodies could be useful. Given its low level of evidence, prolongated treatment by doxycycline, hydroxychloroquine ± anticoagulant for C. burnetii's associated anti-phospholipid syndrome is discussed, but succeeded in our case.

Vessel wall imaging in the diagnosis of antiphospholipid syndrome presenting as Moyamoya syndrome-A case report.

Objectives: We describe a case of anti-phospholipid syndrome (APLS) vasculopathy presenting with Moyamoya syndrome (MMS) and show the associated intracranial vessel wall MRI (VWI) findings. Methods: A 37-year-old-woman presented with acute onset dizziness and left-sided weakness. Neurologic exam revealed a left facial droop and left hemiparesis. She underwent a comprehensive laboratory work-up for stroke. Neuroimaging included a CT head, CT angiogram, VWI, and digital subtraction angiography. Results: Work-up revealed a triple-positive APLS antibody profile. CT of the head showed an acute right basal ganglia infarction and right frontal subarachnoid hemorrhage. CT angiogram revealed severe stenosis of the right internal carotid artery terminus in a Moyamoya pattern. Intracranial VWI showed long-segment concentric vessel wall thickening and homogeneous vessel wall enhancement and T2-hyperintense wall edema of the stenotic right ICA terminus, M1 middle cerebral artery, and A1 anterior cerebral artery. She was treated with long-term anticoagulation with warfarin and a right superficial temporal artery to middle cerebral artery bypass. Discussion: We present intracranial VWI features of vessel wall pathology in a patient with primary APLS presenting with MMS.

Inflammatory and vaso-occlusive ulcers: Part I - clinical presentation and diagnosis.

In this CME, we review two specific categories of ulcers: inflammatory (where inflammation is the primary pathologic process leading to ulceration) and vaso-occlusive (where occlusion is the primary process). Inflammatory ulcers include pyoderma gangrenosum and vasculitides, whereas livedoid vasculopathy, calciphylaxis and Martorell ulcers are vaso-occlusive ulcers. Determining the causes of ulcers in these conditions may require laboratory evaluation, biopsy and imaging.

Inflammatory and vaso-occlusive ulcers: Part II - Management.

In the second part of this CME, we present an approach for the management of inflammatory and vaso-occlusive ulcers and highlight the need for further research in this field. The three overarching principles for management are etiology-specific treatment, ulcer care, and consideration of patient comorbidities and risk factors for poor healing. Both etiology-specific treatment and management of patient comorbidities and risk factors often require collaboration with providers from other specialties. Ulcer care is governed by TIME, or tissue debridement, infection control, management of moisture imbalance and epithelial edge advancement. As wound healing is a dynamic process, management should be adapted to changes in the status of the ulcer.

Recurrent Syncope Unveiling Pulmonary Hypertension Secondary to Pulmonary Artery Thrombi in a Pediatric Patient.

We present a case of a nine-year-old female patient who presented with recurrent syncope and was ultimately diagnosed with pulmonary hypertension (PH) secondary to pulmonary artery thrombi in the context of anti-phospholipid syndrome (APS). Extensive investigations including imaging studies revealed PH. Thromboembolic workup confirmed multiple pulmonary artery thrombi, and anti-phospholipid antibody testing confirmed APS. The patient received anticoagulation therapy tailored to APS management. Follow-up assessments demonstrated significant improvement in PH leading to cessation of syncope episodes. In this case, we underscore the importance of considering rare causes of syncope in the pediatric age group, particularly autoimmune disorders. Timely recognition and appropriate management are crucial for favorable outcomes in such cases. This report contributes to understanding the diverse clinical presentations of APS and emphasizes the need for a comprehensive diagnostic approach in patients with unexplained syncope.

Antiphospholipid syndrome pathogenesis in 2023: an update of new mechanisms or just a reconsideration of the old ones?

Antibodies against phospholipid (aPL)-binding proteins, in particular, beta 2 glycoprotein I (ß2GPI), are diagnostic/classification and pathogenic antibodies in antiphospholipid syndrome (APS). ß2GPI-aPL recognize their target on endothelium and trigger a pro-thrombotic phenotype which is amplified by circulating monocytes, platelets and neutrophils. Complement activation is required as supported by the lack of aPL-mediated effects in animal models when the complement cascade is blocked. The final result is a localized clot. A strong generalized inflammatory response is associated with catastrophic APS, the clinical variant characterized by systemic thrombotic microangiopathy. A two-hit hypothesis was suggested to explain why persistent aPL are associated with acute events only when a second hit allows antibody/complement binding by modulating ß2GPI tissue presentation. ß2GPI/ß2GPI-aPL are also responsible for obstetric APS, being the molecule physiologically present in placental/decidual tissues. Additional mechanisms mediated by aPL with different characteristics have been reported, but their diagnostic/prognostic value is still a matter of research.

Identification of MARK2, CCDC71, GATA2, and KLRC3 as candidate diagnostic genes and potential therapeutic targets for repeated implantation failure with antiphospholipid syndrome by integrated bioinformatics analysis and machine learning.

Background: Antiphospholipid syndrome (APS) is a group of clinical syndromes of thrombosis or adverse pregnancy outcomes caused by antiphospholipid antibodies, which increase the incidence of in vitro fertilization failure in patients with infertility. However, the common mechanism of repeated implantation failure (RIF) with APS is unclear. This study aimed to search for potential diagnostic genes and potential therapeutic targets for RIF with APS. Methods: To obtain differentially expressed genes (DEGs), we downloaded the APS and RIF datasets separately from the public Gene Expression Omnibus database and performed differential expression analysis. We then identified the common DEGs of APS and RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and we then generated protein-protein interaction. Furthermore, immune infiltration was investigated by using the CIBERSORT algorithm on the APS and RIF datasets. LASSO regression analysis was used to screen for candidate diagnostic genes. To evaluate the diagnostic value, we developed a nomogram and validated it with receiver operating characteristic curves, then analyzed these genes in the Comparative Toxicogenomics Database. Finally, the Drug Gene Interaction Database was searched for potential therapeutic drugs, and the interactions between drugs, genes, and immune cells were depicted with a Sankey diagram. Results: There were 11 common DEGs identified: four downregulated and seven upregulated. The common DEG analysis suggested that an imbalance of immune system-related cells and molecules may be a common feature in the pathophysiology of APS and RIF. Following validation, MARK2, CCDC71, GATA2, and KLRC3 were identified as candidate diagnostic genes. Finally, Acetaminophen and Fasudil were predicted as two candidate drugs. Conclusion: Four immune-associated candidate diagnostic genes (MARK2, CCDC71, GATA2, and KLRC3) were identified, and a nomogram for RIF with APS diagnosis was developed. Our findings may aid in the investigation of potential biological mechanisms linking APS and RIF, as well as potential targets for diagnosis and treatment.

Lupus anti-coagulant hypoprothrombinemia syndrome across different ages: a case report and review of the literature.

Lupus anti-coagulant hypoprothrombinemia syndrome (LAHPS) is a rare condition that can be difficult to treat. It increases the risk of thrombosis and bleeding due to the presence of lupus anti-coagulant and factor II deficiency, respectively. There are a limited number of cases described in the literature. Herein we describe a case of LAHPS with bleeding symptoms as a first clinical manifestation of systemic lupus erythematosus (SLE) in an 8-year-old female. She has had multiple recurrences of her bleeding symptoms, requiring treatment with steroids, cyclophosphamide, mycophenolate mofetil, and rituximab. Her course was later complicated by development of arthritis and lupus nephritis. Her complicated course provides a new perspective on the clinical course and treatment of LAHPS. We also present a comprehensive literature review which demonstrates the difficulty in treating patients with LAHPS with underlying SLE and the variability of the clinical course and management of LAHPS depending on the age at presentation.

Stroke with postoperative visual loss as the first clinical manifestation of antiphospholipid antibody syndrome: Case report.

INTRODUCTION: Postoperative visual loss (POVL) is a rare and devastating complication. Its incidence in nonophthamologic surgeries varies from 0.056 % to 1.3 %. Autoimmune rheumatic diseases with a predisposition to thrombotic events, such as antiphospholipid antibody syndrome (APS), may constitute an important risk factor for this complication. PRESENTATION OF CASE: A 34-year-old female patient, who was a former smoker and had no other comorbidities. She underwent orthopedic surgery and presented with bilateral POVL associated with the loss of secondary muscle strength and intraoperative venous and arterial cerebral thrombosis. She was thoroughly investigated regarding the etiology of her condition, and high levels of antiphospholipid antibodies were found. DISCUSSION: APS is an autoimmune disease that predisposes the patient to thrombotic events. Among these, stroke is one of the main causes of POVL secondary to ischemia of the cortical territory, or also known as "cortical blindness." CONCLUSION: The rare incidence of POVL in nonophthalmological surgeries and the consequence and preservation in the literature on the subject, explain the limitations of its pathophysiology, and especially the development of guidelines focused on the prevention of patients with risk factors for this condition. Thus, this case report warns about the risks and anesthetic care that patients with risk factors should have when undergoing nonophthalmological surgeries.

Intravenous Immunoglobulins as Immunomodulators in Autoimmune Diseases and Reproductive Medicine.

Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few diseases, while in most cases, their application is off-label and thus different from their registered therapeutic indications according to the summary of product characteristics. In this review, we present the state-of-the-art use of IVIGs in various autoimmune conditions and immune-mediated disorders associated with reproductive failure, as approved therapy, based on indications or off-label. IVIGs are often an alternative to other treatments, and the administration of IVIGs continues to expand as data accumulate. Additionally, new insights into the pathophysiology of immune-mediated disorders have been gained. Therefore, the need for immunomodulation has increased, where IVIG therapy represents an option for stimulating, inhibiting and regulating various immune processes.

A Curious Case of Occlusive Retinal Vasculitis in a Young Individual Associated with COVID-19 Vaccination.

A 23-year-old man presented with the blurring of vision in the left eye for 4 days. Best-corrected visual acuity was 6/6 N6 in both eyes. Examination revealed an unremarkable right eye while the left eye showed occlusive retinal vasculitis with no retinitis, choroiditis, or macular involvement. Fundus fluorescein angiography confirmed the same. History revealed the patient had received 2nd dose of Covishield vaccination 4 weeks before the onset of symptoms. Blood investigations were negative for infectious or any systemic autoimmune disease. Serum homocysteine and serum CMV IgG levels were grossly increased while tests for antiphospholipid syndrome were weakly positive. He responded well to a combination of intravitreal and oral antivirals, oral steroids for vasculitis and tablets Clopilet and Homin. This case is extremely intriguing in terms of the involvement of the adenoviral vector vaccine either as a causative factor or being just a coincidental finding.

Antiphosphatidylserine/prothrombin antibodies (aPS/PT) and risk of obstetric anti-phospholipid syndrome.

OBJECTIVE: Assessment of the prevalence of anti-phosphatidylserine-prothrombin antibodies (aPS/PT) with OAPS and SN-OAPS in Chinese patients. METHODS: This retrospective study proceeded at Ren Ji Hospital, Shanghai, China, from January 2019 to January 2020. Two hundred eleven OAPS, 68 SN-OAPS, 81 disease controls, and 30 healthy donors were enrolled. IgM and IgG aPS/PT, IgM/IgG - aCL, and IgM/ IgG/ anti-ß2GPI antibodies were tested by ELISA while LAC was tested by clotting assays. All the patients were followed up and tested at least twice over 12 weeks apart. RESULTS: Thirty-three OAPS (15.64%) and 31 SN-OAPS (45.59%) were positive for aPS/PT. aPS/PT IgM showed a high Youden index (.813), which classified OAPS and SN-OAPS patients from healthy controls and other autoimmune diseases. aPS/PT showed a stronger relationship with LAC. Of the 25 OAPS women positive for IgM aPS/PT, 19 (79%) LAC were positive, while of the eight women positive for IgG aPS/PT, 100% were found LAC positive. CONCLUSION: aPS/PT antibody showed an efficient diagnostic value for Chinese patients with OAPS and SN-OAPS, which could be a potential risk predictor for obstetric complications.

Evaluation of Antiphospholipid Antibodies in COVID-19 Patients with Coagulopathy.

Background: Due to the importance of recent published studies regarding the thrombotic events in COVID-19 patients, the purpose of this study was to evaluate the frequency of antiphospholipid antibodies in COVID-19 patients with coagulopathy. Materials and Methods: The present cross-sectional study was conducted on COVID-19 patients with coagulopathy admitted to Imam Khomeini Hospital in Sari, Iran, between June and September in 2020. Later on, the levels of anti-phospholipid antibodies (aPL-ab) and biochemical factors were measured. Results: This study was performed on 40 patients. Individuals who were positive for at least one of the aPL-ab were classified in the group of aPL-ab positive; according to which 29 patients (72.5%) had no positive aPL-ab and 11 patients (27.5%) had at least one positive aPL-ab. 8 patients were only positive for lupus anticoagulant (LA) assay, one patient had B2GPI- IgM, one patient had aCL-IgG and only one patient had two positive simultaneous tests for LA and aCL-IgG. Thrombotic events have been found in 7 patients (17.5%) of which, three patients with deep vein thrombosis, one patient with pulmonary embolism, two patients with stroke, and one patient with myocardial infarction. The values of aPTT for the screening of Lupus anticoagulant assay were significantly different between the two groups, although there was no significant difference between the two groups in the co-morbidities, disease severity, death and laboratory tests (P> 0.05). Conclusion: Despite the high incidence of thrombotic complications reported in COVID-19 patients in the current study, the levels of antiphospholipid antibodies had no significant correlation with the occurrence of thromboembolic events and disease outcome in COVID-19 patients with coagulopathy.

Bilateral Upper Limb Symmetrical Digital Gangrene: A Rare Presentation of Anti-Phospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease present most commonly in young women, characterized by the presence of antibodies against various phospholipids and culminating in alteration of the flow of blood, leading to arterial and venous thrombosis. Although it can present with a wide range of manifestations, digital gangrene is one of the important ones. We present a case of a young female with antiphospholipid syndrome who presented with acute onset bilateral upper limb symmetrical digital gangrene with prior history of multiple fetal losses. Acute onset, symmetrical gangrene, limited to the bilateral upper limbs without venous system involvement, that too in association with systemic lupus erythematosus (SLE) which does not usually manifest as such make this case a unique and interesting one.

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

Background: At the beginning of the SARS-CoV-2 pandemic, there was a lack of information about the infection's impact on pregnancy and capability to induce de novo autoantibodies. It soon became clear that thrombosis was a manifestation of COVID-19, therefore the possible contribution of de novo antiphospholipid antibodies (aPL) raised research interest. We aimed at screening SARS-CoV-2 positive pregnant patients for aPL. Methods: The study included consecutive pregnant women who were hospitalized in our Obstetric Department between March 2020 and July 2021 for either a symptomatic SARS-CoV-2 infection or for other reasons (obstetric complications, labour, delivery) and found positive at the admission nasopharyngeal swab. All these women underwent the search for aPL by means of Lupus Anticoagulant (LA), IgG/IgM anti-cardiolipin (aCL), IgG/IgM anti-beta2glycoprotein I (aB2GPI). Data about comorbidities, obstetric and neonatal complications were collected. Results: 151 women were included. Sixteen (11%) were positive for aPL, mostly at low titre. Pneumonia was diagnosed in 20 women (5 with positive aPL) and 5 required ICU admission (2 with positive aPL). Obstetric complications occurred in 10/16 (63%) aPL positive and in 36/135 (27%) negative patients. The occurrence of HELLP syndrome and preeclampsia was significantly associated with positive aPL (p=0,004). One case of maternal thrombosis occurred in an aPL negative woman. aPL positivity was checked after at least 12 weeks in 7/16 women (44%): 3 had become negative; 2 were still positive (1 IgG aB2GPI + IgG aCL; 1 IgM aB2GPI); 1 remained positive for IgG aCL but became negative for aB2GPI; 1 became negative for LA but displayed a new positivity for IgG aCL at high titre. Conclusions: The frequency of positive aPL in pregnant women with SARS-CoV-2 infection was low in our cohort and similar to the one described in the general obstetric population. aPL mostly presented as single positive, low titre, transient antibodies. The rate of obstetric complications was higher in aPL positive women as compared to negative ones, particularly hypertensive disorders. Causality cannot be excluded; however, other risk factors, including a full-blown picture of COVID-19, may have elicited the pathogenic potential of aPL and contributed themselves to the development of complications.

A novel aGAPSS-based nomogram for the prediction of ischemic stroke in patients with antiphospholipid syndrome.

Background: Ischemic stroke (IS) is the most common and life-threatening arterial manifestation of antiphospholipid syndrome (APS). It is related to high mortality and severe permanent disability in survivors. Thus, it is essential to identify patients with APS at high risk of IS and adopt individual-level preventive measures. This study was conducted to identify risk factors for IS in patients with APS and to develop a nomogram specifically for IS prediction in these patients by combining the adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS) with additional clinical and laboratory data. Methods: A total of 478 consecutive patients with APS were enrolled retrospectively. All patients were randomly assigned to the training and validation cohorts. Univariate and multivariate binary logistic analyses were conducted to identify predictors of IS in the training cohort. Then, a nomogram was developed based on these predictors. The predictive performance of the nomogram for the training and validation cohorts was evaluated by determining areas under the receiver operating characteristic curve (AUROC) and creating calibration plots. A decision curve analysis (DCA) was conducted to compare the potential net benefits of the nomogram with those of the aGAPSS. Results: During a mean follow-up period of 2.7 years, 26.9% (129/478) of the patients were diagnosed with IS. Binary logistic regression analysis revealed that five risk factors were independent clinical predictors of IS: age (P < 0.001), diabetes (P = 0.030), hyperuricemia (P < 0.001), the platelet count (P = 0.001), and the aGAPSS (P = 0.001). These predictors were incorporated into the nomogram, named the aGAPSS-IS. The nomogram showed satisfactory performance in the training [AUROC = 0.853 (95% CI, 0.802-0.896] and validation [AUROC = 0.793 (95% CI, 0.737-0.843)] cohorts. Calibration curves showed good concordance between observed and nomogram-predicted probability in the training and validation cohorts. The DCA confirmed that the aGAPSS-IS provided more net benefits than the aGAPSS in both cohorts. Conclusion: Age, diabetes, hyperuricemia, the platelet count, and the aGAPSS were risk factors for IS in patients with APS. The aGAPSS-IS may be a good tool for IS risk stratification for patients with APS based on routinely available data.

Antiphospholipid Antibody Syndrome in Childhood Systemic Lupus Erythematous With a Unique Presentation: A Case Report.

Initial presentation of childhood systemic lupus erythematosus (SLE) as antiphospholipid syndrome (APS) is uncommon; moreover, APS presenting with both hemorrhage and thrombosis is very rare. We report a case of a previously healthy eight-year-old boy, without any significant past or family history, who presented with ecchymotic patches, epistaxis, and right-side hemiparesis. Investigation showed severe thrombocytopenia and isolated high activated partial thromboplastin time (aPTT) not corrected by mixing study. During his hospital stay, the child developed left-sided focal seizure and digital gangrene as thrombotic events. Neuroimaging revealed initially hemorrhagic stroke and subsequently bilateral infarct of middle cerebral artery (MCA) territory. The child was diagnosed as a case of SLE with APS based on Systemic Lupus International Collaboration Clinics (SLICC) criteria, revised APS classification, clinicoimmunological profile and neuroimaging. As the child was progressing towards catastrophic APS, he was treated aggressively with intravenous pulse methylprednisolone, intravenous cyclophosphamide and plasmapheresis with successful recovery. A simple bleeding manifestation may mask a serious disorder. A simple test like mixing study is helpful in diagnosis and in avoiding unnecessary investigations. A combination of both hemorrhage and thrombosis is an unusual presentation of APS and should always be suspected in case of autoimmune disorder, especially in SLE.