Catastrophic Antiphospholipid Syndrome Research Articles

OA04 Paediatric APS - children are not just small adults

OA04 Paediatric APS - children are not just small adults

Rapidly evolving necrotic skin lesions of the face

Rapidly evolving necrotic skin lesions of the face

Antiphospholipid Antibody Syndrome-Associated Increased Surface Expression of VLA4 Integrin on Human Monocytes.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis and/or obstetric complications in the presence of antiphospholipid antibodies (aPL). Catastrophic APS (CAPS) is the most severe form of the disease, in which microvascular thromboses develop rapidly, leading to multiorgan failure. Monocytes, along with endothelial cells, are critical players in the pathogenesis of APS. Recruitment of these cells to the site of injury/inflammation involves a series of events, including capture, rolling, adhesion enhancement, and transmigration, which are controlled by surface adhesion molecules. The aim of our study was to investigate the surface adhesion profile of monocytes from APS patients and monocytes stimulated in vitro with aPL from a CAPS patient. The surface expression of the adhesion molecules LFA1, L-selectin, MAC1, PSGL1, and VLA4 was analyzed by flow cytometry. To our knowledge, this preliminary study was the first to show that VLA4 was significantly increased on the surface of monocytes from APS patients. Moreover, in vitro stimulations mimicking CAPS showed an even greater increase in VLA4. Our data suggest that the surface adhesion profile on monocytes is altered in APS and CAPS and may be involved in the thrombotic pathophysiology of the disease by enhancing monocyte adhesion.

Cœur et médecine interne : lupus systémique et syndrome des antiphospholipides

Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure.

Neurologic Manifestations of Catastrophic Antiphospholipid Syndrome.

Understanding of antiphospholipid antibody syndrome (APS), associated neurological manifestations, and disease-directed treatment has grown considerably over the last decade. Herein, we critically review the current and high-yield literature related to the pathophysiology, neurological presentations, and management of APS with particular emphasis on the rare and more fatal subset of APS, catastrophic antiphospholipid syndrome (CAPS). APS may manifest with a variety of neurologic syndromes, with cerebrovascular disease representing the most commonly encountered presentation. Diagnostic evaluation and treatment are often tailored to the specific presentation, with suspicion and testing for antiphospholipid antibodies recommended when neurologic presentations occur atypically or in younger individuals. In CAPS, which is more rapidly progressive with multiorgan involvement, potential alternative microangiopathic syndromes should be carefully considered in the differential diagnosis. To date, anticoagulation with vitamin K antagonists remains the mainstay of therapy in APS while triple therapy with anticoagulation, corticosteroids, and plasma exchange is standard of care in CAPS. Immunotherapy has shown early promise in refractory cases. APS is an autoimmune clinical syndrome with neurologic presentations classically characterized by vascular thrombosis, though recent understandings suggest additional direct immune-mediated phenomena. Our understanding of the underlying pathogenic mechanisms of APS continues to grow and will continue to influence our therapeutic approaches.

Update in Hyperferritinemic Syndromes: Recognition and Management - A Scoping Review

Elevated serum ferritin is a marker of macrophage activation and is associated with increased mortality. The hyperferritinemic syndromes which include hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS), catastrophic antiphospholipid syndrome (CAPS), septic shock, adult-onset Still’s Disease (AOSD), and multi-inflammatory syndrome related to COVID-19 (MIS-C/A) are characterized by intense inflammation and its sequalae. Prompt recognition and management of these heterogenous disorders is required to improve patient outcomes. We perform a scoping review of the existing literature on the key features of these rare syndromes.

Suspected COVID-19 Immunization-Induced Probable Catastrophic Antiphospholipid Syndrome

In this report, we describe the case of a woman with suspected COVID-19 immunization-induced probable catastrophic antiphospholipid syndrome. The patient is a 35-year-old female with a past medical history significant for antiphospholipid syndrome, not on anticoagulation, who presented with a 5-day history of abdominal pain and distention, nausea, vomiting, and shortness of breath. She had received her first dose of the Pfizer COVID-19 vaccine one day prior to the onset of symptoms. After extensive workup at an outside hospital, she was found to be in acute heart failure exacerbated by severe mitral and tricuspid regurgitation. She was transferred to our hospital for escalation of care. EKG showed evidence of prior inferior and septal myocardial infarction. Transesophageal echocardiogram (TEE) showed reduced ejection fraction, severe mitral and tricuspid regurgitation, and a left ventricular thrombus. Cardiac MRI showed subendocardial late gadolinium enhancement indicative of ischemia. However, CTA of the coronary vessels showed no signs of obstruction. Therefore, her acute heart failure was thought to be due to small vessel thrombosis secondary to antiphospholipid syndrome. During admission, she had several absence seizure-like episodes. CT head showed several hypodensities of the deep white matter and brain MRI demonstrated multiple hyperintense T2 FLAIR signal foci with restriction diffusion and enhancement involving the cerebral hemisphere, consistent with subacute strokes attributed to being secondary to antiphospholipid syndrome or embolic from the left ventricular thrombus. She was treated with heparin for suspected catastrophic antiphospholipid syndrome and high-dose corticosteroid therapy for concomitant Systemic Lupus Erythematosus (SLE). She was discharged in a stable condition.

The challenges in diagnosing pediatric primary antiphospholipid syndrome

Pediatric primary antiphospholipid syndrome (APS) is a very rare disease with significant distinctions from the APS in adults. Herein, we present our experience in the diagnosis and treatment of six pediatric primary APS patients, who met the updated Sapporo criteria for the APS diagnosis. One of them was also diagnosed as having probable catastrophic APS (CAPS) due to the involvement of three different organ systems simultaneously. Besides vascular involvement, four patients had thrombocytopenia, one had psychiatric disorder, and one had chorea and valvular heart disease. All patients received immunosuppressive treatment along with long-term anticoagulation therapy. Specific neurologic and hematologic manifestations that are not part of the classification criteria can be seen in children with primary APS. Therefore, using the adult criteria for diagnosing pediatric APS may result in missed or delayed diagnoses in children.

The clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome: A descriptive analysis of 73 patients from the "Catastrophic antiphospholipid syndrome registry".

To explore the prevalence and clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome (CAPS). We reviewed data from the "CAPS Registry" on C3 and/or C4 complement plasma protein levels during acute CAPS episodes. Patients were classified into those with low and normal complement levels. Data on clinical presentation, with special focus on thrombotic microangiopathy (TMA) features, diagnosis of systemic lupus erythematosus (SLE), and antiphospholipid antibody (aPL) profile were reviewed. The chi-square exact test was performed to evaluate differences between categorical data. The "CAPS Registry" includes 566 patients with a total of 578 episodes of CAPS. Data on complement plasma protein levels was available in 73 episodes from the same number of patients. Low levels of C3 and/or C4 complement plasma proteins were detected in 42 (58%) CAPS episodes. Low complement levels were more common in SLE patients (55% SLE vs. 19% No SLE; p<0.001). The frequencies of clinical TMA (72% vs. 80%; p=0.4) or TMA syndrome (86% vs. 84%, p=0.9), frequency of triple aPL triple positivity (67% vs 33%; p=0.3), or the mortality (35% vs. 31%; p=0.7) were similar between low and normal complement groups. In our study, low levels of C3 and C4 plasma proteins are detected in 58% episodes of CAPS, which were not associated with clinical presentation including TMA features, aPL triple positivity, or mortality.

A CASE OF INTERMITTENT HEMOPTYSIS: THE SPECTRUM OF ANTIPHOSPHOLIPID ANTIBODY SYNDROME

TYPE: Late Breaking Case Report TOPIC: Pulmonary Manifestations of Systemic Disease INTRODUCTION: A 46 year old WM presented with several years of intermittent hemoptysis. Symptoms resolve spontaneously, improve with diuresis or required antibiotics/steroids. Evaluation for infection was negative and was maintained on daily prednisone with benefit. Malaise, hypoxemia, edema with hemoptysis but no other associated symptoms. CASE PRESENTATION: Past medical history includes CVA at age 24 related to antiphospholipid antibody syndrome and treated with anticoagulation. No other organ involvement reported. Medical history: CKD, HTN, non-ischemic cardiomyopathy. Remote 15PY tobacco history, no other exposures. On exam, room air O2 saturation 92%, desaturation to 70s with exertion. Oropharynx class III Mallampati score, lungs clear, CV RRR, no murmurs, gallops, extremities with lower extremity edema, no clubbing, rashes, ecchymosis, petechiae. Evaluation: negative ANA, DS-DNA, ENA, ANCA, anti-GBM, anti-CCP Ab. Normal immunoglobulins, complements and positive lupus anticoagulant. Chemistries: elevated creatinine, WBC 13.1, Hemoglobin 10.5, platelets 89. BNP 659, normal urinalysis. PFTs: restriction and reduced DLCO. Cardiac echo: moderately dilated LV, LVEF 40%, normal right ventricular size and function. CT chest showed diffuse bilateral pulmonary ground glass opacities. DISCUSSION: Clinical course included empiric antibiotics, bronchoscopy, heart failure management, high-dose steroids, and cyclophosphamide initiation for diffuse alveolar hemorrhage. He had clinical improvement but required readmission with progressive pulmonary symptoms, acute renal failure, and an acute ischemic stroke despite adequate anticoagulation. This met criteria for Catastrophic Antiphospholipid Antibody Syndrome. He was treated with plasma exchange, steroids/cyclophosphamide and rituximab. CONCLUSIONS: This case represents the spectrum of disorders seen in antiphospholipid antibody syndrome. Antiphospholipid antibody syndrome can have a broad range of presentation in the lungs. DISCLOSURE: Nothing to declare. KEYWORD: ANTIPHOSPHOLIPID ANTIBODY SYNDROME

Significance of hyperferritinemia as a diagnostic and prognostic biomarker

Ferritin is a complex protein composite (iron protein) that plays the role of the main intracellular iron depot in humans and animals, consisting of the protein apoferritin and the ferric atom in the composition of phosphate hydroxide. The reference value of ferritin in women is 200 μg/l, in men – 300 μg/l. Ferritin is a marker of total body iron stores, and low levels are specific for iron deficiency. Ferritin is also involved in immune processes and has both pro-inflammatory and immunosuppressive activity. Hyperferritinemia is a nonspecific symptom that occurs in a number of immunoinflammatory, infectious diseases, as well as during body iron stores overload. Hyperferritinemia is a criterion sign of macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis, systemic lupus erythematosus and Kawasaki disease, as well as a predictive biomarker of adult-onset Still's disease. High ferritin levels occur in catastrophic antiphospholipid syndrome, as well as in infectious pathologies such as septic shock and COVID-19, including multisystem inflammatory syndrome associated with COVID-19. Ferritin concentration is an important parameter for assessing the activity and prognosis of the disease, which allows a rational approach to the choice of therapy in these patients.

Early recognition of catastrophic antiphospholipid syndrome in patients with antiphospholipid syndrome based on a Chinese cohort study.

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of antiphospholipid syndrome (APS) with high mortality. We try to develop a predictive model to achieve early recognition of CAPS. Data of APS patients referred into Peking Union Medical College Hospital from May 2013 to October 2021 was collected. A binary logistic regression method was used to identify predictors of CAPS, coefficient B was assigned with score value in the development of prediction model, and risk-stratification was based on the calculated scores using the model. Twenty-seven CAPS (11.9%) occurred in 226 APS patients. CAPS was more likely to occur in male secondary APS patients with a history of hypertension, hyperlipidaemia, and arterial thrombosis, presented with haematological, nephrological and immunological abnormalities simultaneously. Hypertension history (OR 5.091, 95% CI 1.119-23.147), anaemia (OR 116.231, 95% CI 10.512-1285.142), elevated LDH (OR 59.743, 95% CI 7.439-479.815) and proteinuria (OR 11.265, 95% CI 2.118-59.930) were independent predictors for CAPS, and the scores were 1, 3, 3 and 2 points, respectively. The risk scores were divided into high-risk (6-9) and low risk (0-5), the risk for CAPS were 54.1% and 0.6%, with sensitivity of 0.963 and specificity of 0.886. The Nagelkerke's R2 (0.739) and the Omnibus test (χ2 =109.231, df=4, p=0.000) indicated the model has a good fit. The AUC of 0.971 indicated good discrimination. The calibration curve in internal validation showed good calibration of this predictive model. A predictive model of CAPS was developed with hypertension, anaemia, elevated LDH and proteinuria. This model could help identify CAPS in high-risk patients, achieve early recognition and intervention to improve prognosis.

Anticoagulation and Stroke.

In 2019, the American Heart Association did not recommend the emergent use of anticoagulation to prevent recurrence or progression of acute ischemic stroke. However, its indication in patients with extracranial artery intraluminal thrombus with artery-to-artery cerebral embolization must be analyzed. In this article, we will also discuss other indications of anticoagulation. This treatment could be indicated in patients with ischemic stroke caused by embolization from cervical artery dissection, catastrophic antiphospholipid antibodies syndrome (APS) and some cases of Covid 19. For secondary prevention, anticoagulation is recommended for Cardioembolic stroke such as nonvalvular atrial fibrillation and other cardiopathies, some patients with cervical artery dissection, stroke associated with cancer, and thrombophilia such as APS. The timing to restart anticoagulation after a large ischemic stroke or after a cerebral hemorrhagic transformation always represent a challenge. Even in patients with high risk of thromboembolism it should be delayed at least two weeks, ideal after four weeks.

231 Acute Kidney Injury due to Thrombotic Microangiopathy From Catastrophic Antiphospholipid Syndrome Treated With Eculizumab

231 Acute Kidney Injury due to Thrombotic Microangiopathy From Catastrophic Antiphospholipid Syndrome Treated With Eculizumab

All catastrophes are not catastrophic antiphospholipid syndrome

All catastrophes are not catastrophic antiphospholipid syndrome

Liver infarctions as the first manifestation of antiphospholipid antibody syndrome in pregnancy: a case report

BackgroundThe differential diagnosis of abdominal pain in pregnant women is broad. Liver diseases as the origin of abdominal pain in pregnancy are rare, and severe forms occur in less than 0.1% of pregnancies. Some disorders, such as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and preeclampsia, are unique to pregnancy, while others, such as antiphospholipid antibody syndrome, may manifest in pregnancy but have consequences beyond the current pregnancy. All of them require prompt identification and treatment.Case presentationA 27-year-old Caucasian woman who was 15+1 weeks pregnant reported to the emergency department twice due to stabbing right-upper-quadrant abdominal pain. Initial laboratory testing revealed mild leukocytosis and slightly elevated liver enzymes. On second presentation, the patient was febrile and had an increased C-reactive protein concentration. Over the course of the next days, nonhemolytic anemia and thrombocytopenia emerged with elevated liver enzymes. Coagulation studies also revealed a prolongation of activated partial thromboplastin time. Magnetic resonance imaging showed nonspecific alterations in the right liver lobe, possibly corresponding to infection or infarction. A hepatic viral infection was ruled out. At that time, the most likely diagnosis was cholangitis with liver abscess formation, and antibiotic therapy was started. Further worsening of the anemia and thrombocytopenia, development of proteinuria, together with a miscarriage on the fourth day of hospitalization resulted in the tentative diagnosis of (triple-positive) antiphospholipid antibody syndrome, which was confirmed 12 weeks after the initial investigation. Treatment consisted of prompt anticoagulation with heparin and later on with a vitamin K antagonist as well as high-dose glucocorticoid therapy. There was no need for intravenous immunoglobulin therapy or plasma exchange, although we suspected a catastrophic form of antiphospholipid antibody syndrome due to infarctions of the liver, placenta, and possibly kidneys (proteinuria). The outcome was favorable.ConclusionWe report a 27-year-old pregnant woman whose abdominal pain was caused by liver infarctions as the first manifestation of catastrophic antiphospholipid antibody syndrome. The antiphospholipid antibody syndrome was possibly secondary to hitherto clinically silent systemic lupus erythematosus since the antinuclear antibodies were increased later on. Hydroxychloroquine therapy was initiated to prevent antiphospholipid antibody syndrome recurrence in a future pregnancy.

Treatment of catastrophic antiphospholipid syndrome to pregnant woman

The research aimed to study and analyze the life-threatening complication of antiphospholipid syndrome by acute thrombotic microangiopathy, which can lead to multiorgan damage. The progression of catastrophic antiphospholipid syndrome during pregnancy creates a lot of problems in diagnostic due to its extended clinical manifestations and coincidence with additional obstetric intricacies and microangiopathic diseases. Early diagnosis and aggressive treatment (anticoagulants, glucocorticoids, and plasma metabolism (or intravenous immunoglobulins) remain key factors for favorable. In cases of refractory CAPS, cyclophosphamide or monoclonal antibodies (rituximab, eculizumab) should be considered.

Clinical Management of Thrombotic Antiphospholipid Syndrome.

Thrombotic manifestations of antiphospholipid syndrome are often a therapeutic dilemma and challenge. Despite our increasing knowledge of this relatively new disease, many issues remain widely unknown and controversial. In this review, we summarise the latest literature and guidelines on the management of thrombotic antiphospholipid syndrome. These include the laboratory assays involved in antiphospholipid antibodies (aPL) testing, the use of direct oral anticoagulants in secondary prevention, management of recurrent thrombosis, individuals with isolated aPL, and catastrophic antiphospholipid syndrome. Treatment aims to prevent the potentially fatal and often disabling complications of APS with antithrombotic and cardiovascular risks prevention strategies. Some insights and updates on topical issues in APS are provided. We also include our current practice, which we believe is the pragmatic approach based on the currently available evidence.

Interaction between Antiphospholipid Antibodies and Protein C Anticoagulant Pathway: A Narrative Review

Thrombotic antiphospholipid syndrome (APS) is a condition in which thrombosis in venous, arterial, and/or small vessels is ascribed to the presence of antiphospholipid antibodies (aPL). Among the various proposed pathogenic theories to explain thrombotic APS, those involving the interaction between aPL and the protein C system have gained much consensus. Indeed, robust data show an acquired activated protein C resistance (APC-R) in these patients. The role of aPL in this impairment is clear, but the mechanism of action is uncertain, as the type of aPL and to what extent aPL are involved remains a gray area. Lupus anticoagulant (LA) is often associated with APC-R, but antibodies generating LA comprise those directed to β2-glycoprotein I and antiphosphatidylserine/prothrombin. Moreover, the induction of APC-R by aPL requires the presence of phospholipids and is suppressed by the presence of an excess of phospholipids. How phospholipids exposed on the cell membranes work in the system in vivo is unknown. Interestingly, acquired APC-R due to aPL might explain the clinical phenotypes of thrombotic APS. Indeed, the literature reports cases of both venous and arterial thromboembolism as well as skin necrosis, the latter observed in the severe form of protein C deficiency and in catastrophic APS.

Catastrophic antiphospholipid syndrome (Asherson’s syndrome) caused by a suspected intestinal neuroendocrine tumor: a case report

Background. Every year, the number of people with rare forms of the disease is increasing worldwide. One of these is the catastrophic antiphospholipid syndrome — Asherson’s syndrome. To date, it is being actively studied, but the pathophysiological mechanisms of its development have not yet been fully investigated. Our work is the first attempt to describe Asherson’s syndrome on the example of a clinical case in Ukraine. Objective: to determine the factors and mechanisms that led to the death of a patient with Asherson’s syndrome in Ukraine. Materials and methods. The structural-logical analysis and the clinical-statistical method were used. Results. Based on clinical and laboratory criteria, our medical team established a clinical diagnosis of systemic lupus erythematosus complicated by a catastrophic antiphospholipid syndrome (CAPS). Despite treatment with glucocorticoids and anticoagulants according to international guidelines, the patient died. The autopsy results showed that the immediate cause of death was a large blood clot that blocked the pulmonary artery and its main branches. Histological examination revealed thrombosis of small vessels of the kidneys and brain; a neuroendocrine tumor (G2; pT3pNxpM1b) of the small intestine with metastases to the liver, brain, myocardium and kidneys was suspected. An additional immunohistochemical study was performed to clarify the histological diagnosis. The morphological picture and results of immunohistochemical study mostly correspond to the moderately differentiated (G2) non-keratinizing squamous cell carcinoma (ICD-O code: 8070/3) with damage to the walls of the small intestine, liver, lungs, kidneys, myocardium and brain. Conclusions. These data emphasize that despite the rarity of Asherson’s syndrome, it is always necessary to consider its probability in the presence of signs of multiple thrombosis and multiple organ failure. Because its development is the result of serious diseases, including connective tissue diseases, malignancies, infections, the etiotropic and pathogenetic treatment can prevent the development of CAPS and death.