Purtscher-like retinopathy following coronary artery bypass grafting in an antiphospholipid syndrome patient: a case report.

BACKGROUND: Purtscher retinopathy is a rare occlusive microangiopathy comprising a constellation of retinal signs including cotton wool spots, retinal hemorrhages and Purtscher flecken. While classical Purtscher must be antedated by a traumatic incident, Purtscher-like retinopathy is used to refer to the same clinical syndrome in the absence of trauma. Various non-traumatic conditions have been associated with Purtscher-like retinopathy e.g. acute pancreatitis, preeclampsia, parturition, renal failure and multiple connective tissue disorders. In this case study, we report the occurrence of Purtscher-like retinopathy following coronary artery bypass grafting in a female patient with primary antiphospholipid syndrome (APS). CASE PRESENTATION: A 48-year-old Caucasian female patient presented with a complaint of acute painless diminution of vision in the left eye (OS) that occurred approximately two months earlier. Clinical history revealed that the patient underwent coronary artery bypass grafting (CABG) two months earlier and that visual symptoms started 4 days thereafter. Furthermore, the patient reported undergoing percutaneous coronary intervention (PCI) one year before for another myocardial ischemic event. Ophthalmological examination revealed multiple yellowish-white superficial retinal lesions i.e. cotton-wool spots, exclusively in the posterior pole and predominantly macular within the temporal vascular arcades only OS. Fundus examination of the right eye (OD) was normal and the anterior segment examination of both eyes (OU) was unremarkable. A diagnosis of Purtscher-like retinopathy was made based on clinical signs, suggestive history and consolidated by fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) of macula, optic nerve head (ONH) according to the diagnostic guidelines of Miguel. The patient was referred to a rheumatologist to identify the underlying systemic cause and was diagnosed with primary antiphospholipid syndrome (APS). CONCLUSIONS: We report a case of Purtscher-like retinopathy complicating primary antiphospholipid syndrome (APS) following coronary artery bypass grafting. This conveys a message to clinicians that patients presenting with Purtscher-like retinopathy should undergo meticulous systemic work-up in order to identify potentially life-threatening underlying systemic diseases.

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.

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.

Catastrophic Antiphospholipid Syndrome as a Complication of COVID-19 Infection.

COVID-19 infection has been found to precipitate hypercoagulability and transiently increase antiphospholipid antibodies. However, it is yet to be determined how likely these transient changes contribute to thrombotic events and antiphospholipid syndrome. We present a case in which antiphospholipid antibodies were detected in the presence of significant thromboses. The patient was subsequently treated for suspected catastrophic antiphospholipid syndrome following COVID-19 infection.

Antiphospholipid antibodies: what is new in 2022 / Détection des anticorps antiphospholipides : actualités en 2022

Antiphospholipid syndrome (APS) is a clinicobiological entity defined by the association of thrombotic events and/or obstetric complications and the presence of persistent antiphospholipid antibodies (aPLs) detected by coagulation tests (lupus anticoagulant, LAC) and/or immunological assays (anticardiolipin and anti-glycoprotein-beta-I antibodies). The increased use of direct oral anticoagulants (DOAC) for the treatment of venous thromboembolism (VTE) is now a challenge for hematology laboratories for the diagnosis of APS. DOAC interfere with LAC screening and confirmation tests resulting in a risk of false positive results. To avoid these interferences, several solutions are suggested. Some of them rely on the use of DOAC-reversal systems (activated charcoal tablet, filter system) others on the use of reagents insensitive to DOAC presence in the sample. Detection of anti-phosphatidylserine/prothrombin antibodies may be helpful because they are strongly associated to the presence of LAC and are increasingly recognized as a useful tool in the diagnosis and prognosis of APS. Finally, positivity of LA in the setting of a viral infection is frequent and not specific to APS. During the Covid-19 pandemic, many patients developed arterial and VTE that could suggest testing for aPLs. The association between LAC and a risk of VTE or in-hospital mortality in hospitalized Covid-19 patients was not demonstrated. Moreover, aPLs do not persist after Covid-19. Currently, testing for aPLs in Covid-19 patients is not recommended.

Le syndrome des antiphospholipides (SAPL) est une entité clinico-biologique définie par l'association de manifestations thrombotiques et/ou de complications obstétricales et la présence persistante d'anticorps antiphospholipides (aPLs) détectés par des tests de coagulation (lupus anticoagulant, LA) et/ou par des tests immunologiques (anticorps anti-cardiolipine et anticorps anti-ß2-glycoprotéine-I). L'essor des anticoagulants oraux directs (AOD) dans la prise en charge des évènements thrombotiques veineux (ETV) constitue aujourd'hui un défi pour les laboratoires d'hémostase dans le cadre du diagnostic du SAPL. Les AOD interfèrent avec les tests de dépistage et de confirmation du LA occasionnant des faux positifs. Afin de se soustraire à ces interférences plusieurs solutions sont proposées. Certaines reposent sur l'utilisation de système neutralisant l'AOD (pastille de charbon activé, système de filtre) d'autres sur l'utilisation de réactifs insensibles à la présence d'AOD. On peut également faire appel aux anticorps anti-phosphatidylsérine/prothrombine très corrélés à la présence de LA et constituant un outil de plus en plus reconnu dans le diagnostic biologique du SAPL et son pronostic. Enfin, la positivité des aPLs dans un contexte infectieux est fréquente et non spécifique du SAPL. Au cours de la pandémie Covid-19, de nombreux patients ont présentés des ETV et artériels qui ont pu motiver la recherche d'aPLs. L'association entre LA et le risque d'ETV ou la mortalité hospitalière chez les patients Covid-19 hospitalisés n'a pas été démontrée. De plus, il ne semble pas qu'il y ait de persistance de ces aPLs après la Covid-19. A ce jour, la recherche d'aPLs chez les patients atteint de Covid-19 n'est pas recommandée.

Rapidly progressive ischemic strokes and transient antiphospholipid syndrome during a mild SARS-CoV-2 infection.

SARS-CoV-2 infection is associated with an increased risk of thrombotic events, especially during severe forms of disease. Here we describe the clinical history of a patient with a mild form of Covid-19 infection presenting with multiple cerebral ischemic lesions that evolved in an atypical way.

The clinical significance of antiphospholipid antibodies in COVID-19 infection.

INTRODUCTION: One of the factors that may aggravate the clinical presentation in COVID-19 is the increased level of antiphospholipid antibodies (aPLs) and thrombotic events that can be seen with the disease. In our retrospective study, we aimed to evaluate the effect of aPLs on the clinical findings in patients with a diagnosis of COVID-19. METHODOLOGY: Seventy-three patients diagnosed with COVID-19 and examined for aPLs were included in the study. Patients were divided into two groups according to the test results of aPLs. Clinical and laboratory parameters were compared in both groups to reveal whether there was any difference between the groups. RESULTS: There were 15 patients with a positive aPLs test. Dyspnea, nausea, vomiting, myalgia, and abdominal pain were significantly higher in the aPLs positive group than those with negative aPLs. The duration of hospital stays and the need for oxygen therapy of the patients in the aPLs positive group were significantly higher than the aPLs negative group. However, no difference was found between the two groups in terms of mechanical ventilation need, intensive care admission rate, thrombosis and mortality. In terms of laboratory findings, those with positive aPLs have higher median C-reactive protein (CRP) and ferritin values than those with negative aPLs. CONCLUSIONS: In our study group, we could not find a relationship between aPLs positivity and critical complications. According to our hypothesis, it may not be necessary to routinely examine aPLs in patients with a diagnosis of COVID-19 to determine the risk of thromboembolic complications.

Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia propelled by circulating antiphospholipid antibodies that herald vascular thrombosis and obstetrical complications. Antiphospholipid antibodies recognize phospholipids and phospholipid-binding proteins and are not only markers of disease but also key drivers of APS pathophysiology. Thrombotic events in APS can be attributed to various conspirators including activated endothelial cells, platelets, and myeloid-lineage cells, as well as derangements in coagulation and fibrinolytic systems. Furthermore, recent work has especially highlighted the role of neutrophil extracellular traps (NETs) and the complement system in APS thrombosis. Beyond acute thrombosis, patients with APS can also develop an occlusive vasculopathy, a long-term consequence of APS characterized by cell proliferation and infiltration that progressively expands the intima and leads to organ damage. This review will highlight known pathogenic factors in APS and will also briefly discuss similarities between APS and the thrombophilic coagulopathy of COVID-19.

Summary of the 12th Meeting of the European Forum on antiphospholipid antibodies ONLINE.

As a result of the current COVID-19 pandemic, the 12th meeting of the European Forum on Antiphospholipid Antibodies was held in a digital format on 26th March 2021. Even experienced for the first time in a virtual set-up, it kept its strength in continuation of the opportunity for more than 200 physicians from all continents and 20 countries to meet the experts in the field. Contemporary research in the area of antiphospholipid syndrome was presented, and proposals for the new research projects, as a distinguishing feature of the meeting, made a major contribution. Despite challenging times, this meeting enabled the highest number of registered participants to have interactive communication with presenters. This report summarizes major studies and new research projects presented during the online forum meeting.

Coronavirus-disease-2019-induced antiphospholipid-like syndrome: a case report.

BACKGROUND: This paper describes a case of antiphospholipid syndrome-like condition caused by coronavirus disease 2019. The medical community still faces many diagnostic and therapeutic challenges vis-à-vis coronavirus disease 2019. Ultimately, coronavirus disease 2019 is diagnosed on the basis of laboratory and radiological findings. Considering the high rate of mortality due to coagulation abnormalities and thrombosis among coronavirus disease 2019 patients, it is important to pay attention to the differential diagnoses of coronavirus disease 2019 and other diseases following thrombotic events. CASE DESCRIPTION: The patient was a 56-year-old Iranian man who underwent coronary artery bypass graft surgery and mitral valve repair. During hospitalization, the patient showed an elevated level of anticardiolipin antibody (immunoglobulin G isotype), antiphospholipid antibodies, and thrombosis in the brachial artery of the left hand, based on which a differential diagnosis of antiphospholipid syndrome was made. However, ultimately, the coronavirus disease 2019 polymerase chain reaction test and computed tomography scan of the lungs showed that the patient had coronavirus disease 2019. CONCLUSION: According to the few studies performed on coronavirus disease 2019 patients, elevated levels of the isotypes of antiphospholipid antibodies in coronavirus disease 2019 patients create conditions similar to antiphospholipid syndrome, which, in the absence of reliable coronavirus disease 2019 testing, can lead to misdiagnosis and consequently delayed or improper treatment. Therefore, to provide timely and appropriate treatment, it is important to pay attention to differential diagnosis.

Catastrophic antiphospholipid syndrome during pregnancy.

Catastrophic antiphospholipid syndrome (CAPS) is an uncommon and the most severe form of antiphospholipid syndrome (APS). A 33-week pregnant patient with Klippel-Trenaunay syndrome, past SARS-CoV-2 infection and type I fetal growth restriction with shortening of the fetal long bone was diagnosed in our center with a probable CAPS. Cesarean section was performed four days after the diagnosis due to the torpid evolution of the patient. Clinical improvement was noted a few days later and the mother and baby were discharged within a week. We review the current literature on CAPS during pregnancy and provide an updated view.

Is Lupus Anticoagulant a Significant Feature of COVID-19? A Critical Appraisal of the Literature.

The term "lupus anticoagulant (LA)" identifies a form of antiphospholipid antibodies (aPLs) causing prolongation of clotting tests in a phospholipid concentration-dependent manner. LA is one of the laboratory criteria identified in patients with antiphospholipid (antibody) syndrome (APS). The presence of LA in patients with APS represents a significant risk factor for both thrombosis and pregnancy morbidity. There have been several reports of similarities between some of the pathophysiological features of COVID-19 and APS, in particular the most severe form, catastrophic APS. There have also been many reports identifying various aPLs, including LA, in COVID-19 patients. Accordingly, a very pertinent question arises: "Is LA a feature of COVID-19 pathology?" In this review, we critically appraise the literature to help answer this question. We conclude that LA positivity is a feature of COVID-19, at least in some patients, and potentially those who are the sickest or have the most severe infection. However, many publications have failed to appropriately consider the many confounders to LA identification, being assessed using clot-based assays such as the dilute Russell viper venom time, the activated partial thromboplastin time (aPTT), and the silica clotting time. First, most patients hospitalized with COVID-19 are placed on anticoagulant therapy, and those with prior histories of thrombosis would possibly present to hospital already on anticoagulant therapy. All anticoagulants, including vitamin K antagonists, heparin (both unfractionated heparin and low-molecular-weight heparin), and direct oral anticoagulants affect these clot-based assays. Second, C-reactive protein (CRP) is highly elevated in COVID-19 patients, and also associated with severity. CRP can also lead to false-positive LA, particularly with the aPTT assay. Third, persistence of aPL positivity (including LA) is required to identify APS. Fourth, those at greatest risk of thrombosis due to aPL are those with highest titers or multiple positivity. Most publications either did not identify anticoagulation and/or CRP in their COVID-19 cohorts or did not seem to account for these as possible confounders for LA detection. Most publications did not assess for aPL persistence, and where persistence was checked, LA appeared to represent transient aPL. Finally, high titer aPL or multiple aPL positivity were in the minority of COVID-19 presentations. Thus, at least some of the reported LAs associated with COVID-19 are likely to be false positives, and the relationship between the detected aPL/LA and COVID-19-associated coagulopathy remains to be resolved using larger and better studies.

Neurologic Manifestations of the Antiphospholipid Syndrome - an Update.

PURPOSE OF REVIEW: In recent years, the spectrum of neurological manifestations of antiphospholipid syndrome (APS) has been growing. We provide a critical review of the literature with special emphasis on presentation, proposed mechanisms of disease, and treatment of neurological involvement in APS. RECENT FINDINGS: Although stroke is the most common cause of neurological manifestations in patients with APS, other neurological disorders have been increasingly associated with the disease, including cognitive dysfunction, headache, and epilepsy. Direct oral anticoagulants have failed to show non-inferiority compared to vitamin K antagonists for the prevention of major thrombotic events. Antiphospholipid antibodies are often found in patients with acute COVID-19 but clear evidence supporting an association between these antibodies and the risk of thrombotic events, including stroke and cerebral venous thrombosis, is still lacking. APS patients may present with several distinct neurological manifestations. New criteria will facilitate the classification of patients presenting with increasingly recognized non-criteria neurological manifestations.

Failure of Anticoagulation to Prevent Stroke in Context of Lupus-Associated Anti-Phospholipid Syndrome and Mild COVID-19.

Hypercoagulability and virally-mediated vascular inflammation have become well-recognized features of the SARS-CoV-2 virus infection, COVID-19. Of growing concern is the apparent ineffectiveness of therapeutic anticoagulation in preventing thromboembolic events among some at-risk patient subtypes with COVID-19. We present a 43-year-old female with a history of seropositive-antiphospholipid syndrome and systemic lupus erythematosus who developed an acute ischemic stroke in the setting of mild COVID-19 infection despite adherence to chronic systemic anticoagulation. The clinical significance of SARS-CoV-2-mediated endothelial cell dysfunction and its potential to cause macrovascular events in spite of full anticoagulation warrants further investigation and likely represents another disease-defining pathology of COVID-19.

Antiphospholipid antibodies in COVID-19-associated pneumonia patients in intensive care unit.

OBJECTIVES: Antiphospholipid antibodies (APAs) increase the risk of excessive blood clotting, but their role in COVID-19 remains unclear. We aimed to investigate the presence of conventional APAs used in the classification of antiphospholipid antibody syndrome in patients with severe lung infection with SARS-CoV-2 and to compare these results with non-COVID-19 critically ill patients. METHODS: Thirty-one COVID-19 patients (COVID group) and 28 non-COVID-19 critically ill patients (non-COVID group), were included in the study. Anti-cardiolipin (ACA) (IgG, IgM), anti-ß2-glycoprotein 1 (Anti-ß2GPI) (IgG, IgM, and IgA), and if the patient had not received any anti thrombotic agent before blood collection, lupus anticoagulant (LAC) tests were studied from the plasma of the patients. For testing ACA and Anti-ß2GPI, ELISA method was used, while fully automated coagulometer device was used for LAC test. RESULTS: APAs were positive in 25.81% in the COVID group (8/31) and 25% in the non-COVID group (7/28). LAC was the most common APA present in 23.08% of the COVID-19 group, who underwent measurement (6/26), while 3.57% of the non-COVID group was LAC positive (1/28) (p = .047). In the COVID group, ACA IgM, and IgG were positive in 6.45% and 0%, respectively (2/31 vs 0/31). In the non-COVID group, ACA IgM was not positive in any patient, while ACA IgG was positive in 7.14% (2/28). Anti-ß2GPI IgG and IgM tests were not positive in any patient in either the COVID or the non-COVID group. Anti-ß2GPI IgA were positive in 6.45% and 14.29%, respectively (2/31 vs 4/28). CONCLUSION: In this study, APAs were equally positive in critically ill patients among COVID-19 or non-COVID-19 patients. Only LAC was more observed in COVID-19 patients.

High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019.

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.