Catastrophic antiphospholipid syndrome: Lessons from the "CAPS Registry".

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening clinical condition that represents the most severe clinical presentation of the antiphospholipid syndrome (APS). It was first described in 1992 in a group of patients that presented with multiorgan involvement and microangiopathic features of APS. Most of the current knowledge of CAPS comes from the analysis of all cases collected at the "CAPS Registry" that was created in 2000 to perform studies on this condition. Most cases are triggered by a prothrombotic situation that leads to a multiorgan thrombosis and a cytokine storm. The analysis of cases included in the "CAPS Registry" has shown that the triple therapy with anticoagulation, glucocorticoids, and plasma exchange and/or intravenous immunoglobulins is associated to a better prognosis of CAPS. The improvement of the knowledge allowed a decrease from the 50% mortality rate reported in the first series to 25-30% in the most recent publications.

A Genome-Wide Association Study Suggests New Susceptibility Loci for Primary Antiphospholipid Syndrome.

OBJECTIVE: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS. METHODS: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases. RESULTS: We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near HLA-DRA and in STAT1-STAT4 with a genome-wide level of significance; 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele near HLA-DRA is associated with overexpression of HLA-DRB6, HLA-DRB9, HLA-DQA2, and HLA-DQB2 in immune cells, vascular tissue, and nervous tissue. This association is independent of the association between PAPS and HLA-DRB1*1302. Functional analyses highlighted immune-related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren syndrome, suggesting co-localized causal variations close to STAT1-STAT4, TNPO3, and BLK. CONCLUSION: This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.

Tailoring the treatment of inflammatory rheumatic diseases by a better stratification and characterization of the clinical patient heterogeneity. Findings from a systematic literature review and experts' consensus.

Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders. In fact, the resulting patient heterogeneity may be driven by differences in underlying molecular pathology also resulting in variable responses to immunosuppressive drugs. Thus, the identification of different clinical subsets may possibly overcome the major obstacles that limit the development more effective therapeutic strategies for these patients with inflammatory rheumatic diseases. This clinical heterogeneity could require a diverse therapeutic management to improve patient outcomes and increase the frequency of clinical remission. Therefore, the importance of better patient stratification and characterization is increasingly pointed out according to the precision medicine principles, also suggesting a new approach for disease treatment. In fact, based on a better proposed patient profiling, clinicians could more appropriately balance the therapeutic management. On these bases, we synthetized and discussed the available literature about the patient profiling in regard to therapy in the context of inflammatory rheumatic diseases, mainly focusing on randomized clinical trials. We provided an overview of the importance of a better stratification and characterization of the clinical heterogeneity of patients with inflammatory rheumatic diseases identifying this point as crucial in improving the management of these patients.

Evaluation of a novel particle-based assay for detecting SLE-related autoantibodies.

Anti-dsDNA, anti-Sm, and anti-ribosomal-P autoantibodies are hallmarks of systemic lupus erythematosus (SLE), being anti-dsDNA and anti-Sm included in 2019-ACR/EULAR SLE-Classification Criteria. Enzyme-linked (ELISA) and chemiluminescence assays (CIA) are widely established in immunology laboratories, but new technologies, such as particle-based multi-analyte technology (PMAT), are nowadays available. The present study aimed to compare the presence of anti-dsDNA and anti-Sm autoantibodies measured by CIA and PMAT and analyze diagnostic and clinical SLE activity performance. Anti-ribosomal-P autoantibodies by PMAT were also included. Consequently, anti-dsDNA and anti-Sm detected by CIA showed substantial agreement with PMAT (Cohen's kappa = 0.662 and 0.671, respectively). Anti-dsDNA autoantibodies measured by PMAT showed a positive correlation with clinical SLEDAI-2K (p < 0.001) and a negative correlation with complement consumption (p < 0.001). Anti-Sm and anti-ribosomal-P autoantibodies showed a positive correlation with SLEDAI-2K (p < 0.001 and p = 0.001, respectively) and a negative correlation with complement consumption (p < 0.001 and p = 0.001, respectively). Finally, anti-Sm autoantibodies were associated with renal involvement (p < 0.05).

Disease phenotypes in adult patients with suspected undifferentiated autoinflammatory diseases and PFAPA syndrome: Clinical and therapeutic implications.

BACKGROUND: Undifferentiated autoinflammatory diseases are characterized by recurrent or persistent fever, usually combined with other inflammatory manifestations, and negative or inconclusive genetic studies for monogenic autoinflammatory disorders. AIMS: To define and characterize disease phenotypes in adult patients diagnosed in an adult reference center with undifferentiated autoinflammatory diseases, and to analyze the efficacy of the drugs used in order to provide practical diagnostic and therapeutic recommendations. METHODS: Retrospective study (2015-2022) of patients with undifferentiated autoinflammatory diseases among all patients visited in our reference center. Demographic, clinical, laboratory features and detailed therapeutic information was collected. RESULTS: Of the 334 patients with a suspected autoinflammatory disease, 134 (40%) patients (61% women) were initially diagnosed with undifferentiated autoinflammatory diseases. Mean age at disease onset and at diagnosis was 28.7 and 37.7 years, respectively. In 90 (67.2%) patients, symptoms started during adulthood. Forty-four (32.8%) patients met diagnostic/classification criteria for adult PFAPA syndrome. In the remaining patients, four additional phenotypes were differentiated according to the predominant manifestations: a) Predominantly fever phenotype (n = 18; 13.4%); b) Predominantly abdominal/pleuritic pain phenotype (n = 9; 6.7%); c) Predominantly pericarditis phenotype (n = 18; 13.4%), and d) Complex syndrome phenotype (n = 45; 33.6%). Prednisone (mainly on demand), colchicine and anakinra were the drugs commonly used. Overall, complete responses were achieved with prednisone in 41.3%, colchicine in 40.2%, and anakinra in 58.3% of patients in whom they were used. By phenotypes, prednisone on demand was more effective in adult PFAPA syndrome and colchicine in patients with the abdominal/pleuritic pain pattern and PFAPA syndrome. Patients with complex syndrome achieved complete responses with prednisone (21.9%), colchicine (25.7%) and anakinra (44.4%), and were the group more often requiring additional immunosuppressive drugs. CONCLUSIONS: The analysis of the largest single-center series of adult patients with undifferentiated autoinflammatory diseases identified and characterized different disease phenotypes and their therapeutic approaches. This study is expected to contribute to increase the awareness of physicians for an early identification of these conditions, and to provide the best known therapeutic options.

Factors associated with early hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

PURPOSE: Hydroxychloroquine is currently recommended for the treatment of systemic lupus erythematosus (SLE), but it can cause irreversible retinal toxicity. This study aimed to identify factors associated with early hydroxychloroquine-induced retinal toxicity in patients with SLE from a single centre for 20 years. METHODS: SLE patients diagnosed between 1998 and 2017 and followed up for at least 1 year were included. Demographic, clinical, laboratory and therapeutic data were collected from the electronic medical records and retrospectively analysed. Early hydroxychloroquine-induced retinal toxicity was defined as the development of macular toxicity within the first 5 years of hydroxychloroquine treatment. RESULTS: A total of 345 patients followed for a median of 15 years were analysed; 337 (97.7%) patients received hydroxychloroquine, 38 (11.3%) of them presented with retinal toxicity, and 10 (3%) developed early retinal toxicity. These patients had a mean treatment duration of 3.3 years with a mean cumulative dose of 241 g. Patients were diagnosed by visual field (VF) and fundoscopy, and two were also assessed using spectral domain optical coherence tomography (SD-OCT). The median (IQR) age of patients with early toxicity was 56 (51-66) years, and 80% were female. Factors independently associated with early hydroxychloroquine-induced retinal toxicity were lupus anticoagulant positivity (OR 4.2; 95% CI 1.2-15.5) and hypercholesterolaemia (OR 5.6; 95% CI 1.5-21.5). CONCLUSION: Our results suggest that lupus anticoagulant positivity and hypercholesterolaemia among SLE patients may be risk factors for early hydroxychloroquine-induced retinal toxicity, regardless of the dose or duration of treatment.

New proposal for a multimodal imaging approach for the subclinical detection of hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

OBJECTIVE: To compare multimodal structural and functional diagnostic methods in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine, to identify the best complementary approach for detecting subclinical retinal toxicity. METHODS: A cross-sectional, unicentric study was conducted on patients with SLE treated with hydroxychloroquine. Each patient underwent a comprehensive ophthalmic evaluation, comprising structural tests (spectral-domain optical coherence tomography (SD-OCT), en face OCT, en face OCT angiography (OCTA), fundus autofluorescence (FAF)) and functional tests (automated perimetry for visual field (VF) testing, multifocal electroretinography (mfERG)). A diagnosis of macular toxicity required the presence of abnormalities in at least one structural and functional test. The Kappa Concordance Index was used to assess the concordance among the different tests in detecting potential macular toxicity-associated alterations. RESULTS: Sixty-six patients with SLE (132 eyes) were consecutively enrolled. Four (6.1%) patients developed subclinical hydroxychloroquine-induced retinal toxicity without visual acuity impairment. The proportion of abnormal results was 24% for both en face OCT and en face OCTA. Regarding functional analysis, VF was less specific than mfERG in detecting subclinical retinal toxicity (VF specificity 47.5%). En face OCT and en face OCTA structural findings showed better concordance, with a kappa index >0.8, and both identified the same cases of toxicity as FAF. CONCLUSION: Although structural OCT and VF are frequently used to screen for hydroxychloroquine-induced retinal toxicity, our findings suggest that a combination of mfERG, en face OCT and en face OCTA could improve the diagnostic accuracy for subclinical retinal damage. This study emphasises the importance of a multimodal imaging strategy to promptly detect signs of hydroxychloroquine-induced retinal toxicity.

Cardiac involvement in the catastrophic antiphospholipid syndrome (CAPS): Lessons from the "CAPS registry".

OBJECTIVE: To analyze the demographic, clinical, and laboratory characteristics of catastrophic antiphospholipid syndrome (CAPS) patients with cardiac involvement, and to identify the factors associated with this cardiac involvement. MATERIAL AND METHODS: Based on the analysis of the "CAPS Registry", the demographic, clinical, and serological characteristics of patients with cardiac involvement were analyzed. Cardiac involvement was defined as heart failure, valvular disease, acute myocardial infarction, pericardial effusion, pulmonary arterial hypertension, systolic dysfunction, intracardiac thrombosis, and microvascular disease. Univariate and multivariate analysis was used for multiple comparisons. RESULTS: 749 patients (293 [39 %] women and mean age 38.1 ± 16.2 years) accounting for 778 CAPS events were included, of them 404 (52 %) had cardiac involvement. The main cardiac manifestations were heart failure in 185/377 (55 %), valve disease in 116/377 (31 %), and acute myocardial infarction in 104/378 (28 %). Of 58 patients with autopsy/biopsy, 48 (83 %) had cardiac thrombotic microangiopathy, Stroke (29% vs. 21 %, p = 0.012), transient cerebral vascular accident (2% vs. 1 %, p = 0.005), pulmonary infarction (26% vs. 3 %, p = 0.017), renal infarction (46% vs. 35 %, p = 0.006), acute kidney injury (70% vs. 53 %, p < 0.001), and livedo reticularis (24% vs. 17 %, p = 0.016) were significantly more frequent during CAPS events with versus without heart involvement. Multivariate analysis identified acute kidney injury (OR 1.068, IC 95 % 1.8-4.8, p < 0.001) as the only clinical characteristics that were, independently, associated with cardiac involvement in CAPS events. Cardiac involvement was not related to higher mortality. CONCLUSIONS: Cardiac involvement is frequent in CAPS, with association with kidney involvement, and it is not related to higher mortality. The presence of cardiac microthrombosis was demonstrated in most biopsies/autopsies performed.

Risk of diabetes mellitus in systemic lupus erythematosus: systematic review and meta-analysis.

OBJECTIVE: To investigate the risk of DM and evaluate the impact of SLE therapies on the risk of developing DM in patients with SLE. METHODS: Electronic database searches of PubMed, Embase, Cochrane Library and Web of Science were performed from inception to February 2023. Cohort and cross-sectional studies that analysed the risk of DM in patients with SLE were included. The associations between diabetes and antirheumatic agents, such as antimalarials and glucocorticoids, were analysed in cohort studies. Data were pooled using fixed- or random-effects meta-analysis to estimate pooled odd ratios (OR), relative risks (RR) and 95% confidence intervals (CIs). This study was registered with PROSPERO (CRD42023402774). RESULTS: A total of 37 studies (23 cross-sectional and 14 cohort studies) involving 266 537 patients with SLE were included. The pooled analyses from cross-sectional studies and cohort studies did not show an increased risk of DM in SLE patients (OR = 1.05, 95% CI 0.87-1.27; P = 0.63 and RR = 1.32, 95% CI 0.93-1.87; P = 0.12, respectively). However, several cohort studies consistently demonstrated a reduced risk of diabetes with antimalarials, while glucocorticoid use has been associated with an increased risk of developing diabetes. Age, sex, hypertension and immunosuppressants have not been identified as risk factors for DM in SLE patients. CONCLUSION: Although there was no increased risk of DM in patients with SLE compared with controls, HCQ users or adherents had a decreased risk, whereas glucocorticoid users had an increased risk.

Phenotypes in antiphospholipid syndrome: A hierarchical cluster analysis based on two independent databases.

BACKGROUND: Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by thromboses at various sites and obstetric events associated with the persistent presence of antiphospholipid antibodies. The identification of clinical phenotypes in APS patients is a clinical need. In this study, we aimed to determine the clinical phenotypes of APS patients through an unsupervised analysis of two well-characterized cohorts of APS patients. PATIENTS AND METHODS: APS phenotypes were defined by an ascending hierarchical cluster analysis to identify preferential associations between 18 types of organ involvement and clinical characteristics. This analysis was performed on an initial multi-center cohort of 1000 patients, with validation in a replication cohort of 435 patients. RESULTS: The hierarchical analysis identified three APS phenotypes in both the initial and replication cohorts: an obstetric phenotype (n = 259 and n = 74 patients, respectively), a venous thrombosis phenotype, accounting for the largest number of patients (n = 461 and n = 297 patients, respectively), and a skin-central nervous system-heart phenotype (n = 280 and n = 64 patients, respectively). The clinical characteristics of the patients differed significantly between the three phenotypes, but there was no difference in antiphospholipid antibody profile between the groups. CONCLUSIONS: We identified three phenotypes of APS defined based on preferential associations of organ involvements and differences in presentation. These observations may help clinicians to detect organ involvement and to manage treatment.

What we know and what we don't know about catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a severe condition with high mortality. Since its description in 1992, an important effort has been made to improve and disseminate knowledge on CAPS. Most of our current knowledge comes from the studies performed using the CAPS Registry, a database created in 2000 to gather as many cases as possible in order to better define this disease. It has demonstrated that this condition has multiple faces and is often triggered by a precipitating factor that leads to a thrombotic microangiopathy and cytokine storm involving almost any organ of the body. Analysis of the CAPS Registry has also shown that patients receiving anticoagulation, glucocorticoids and plasma exchange and/or IVIG have a better prognosis. However, there are still many unresolved questions. In this review we summarize what is known and what is still a matter of research in this condition.

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee.

Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated.

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort.

OBJECTIVES: To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE). METHODS: We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission. RESULTS: We analysed data from 321 patients; 40.8% were in LLDAS, and 17.4% in DORIS remission. After exclusion of patients in remission, 28.3% were in LLDAS. Overall, 604 pathways differed significantly in LLDAS versus non-LLDAS patients with an false-discovery rate-corrected p (q)<0.05 and a robust effect size (dr)≥0.36. Accordingly, 288 pathways differed significantly between DORIS remitters and non-remitters (q<0.05 and dr≥0.36). DEPs yielded distinct molecular clusters characterised by differential serological, musculoskeletal, and renal activity. Analysis of partially overlapping samples showed no DEPs between LLDAS and DORIS remission. Drug repurposing potentiality for treating SLE was unveiled, as were important pathways underlying active SLE whose modulation could aid attainment of LLDAS/remission, including toll-like receptor (TLR) cascades, Bruton tyrosine kinase (BTK) activity, the cytotoxic T lymphocyte antigen 4 (CTLA-4)-related inhibitory signalling, and the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome pathway. CONCLUSIONS: We demonstrated for the first time molecular signalling pathways distinguishing LLDAS/remission from active SLE. LLDAS/remission was associated with reversal of biological processes related to SLE pathogenesis and specific clinical manifestations. DEP clustering by remission better grouped patients compared with LLDAS, substantiating remission as the ultimate treatment goal in SLE; however, the lack of substantial pathway differentiation between the two states justifies LLDAS as an acceptable goal from a biological perspective.

Thrombosis recurrence and major bleeding in non-anticoagulated thrombotic antiphospholipid syndrome patients: Prospective study from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) clinical database and repository ("Registry").

BACKGROUND: Long-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice. OBJECTIVES: To prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups. PATIENTS/METHODS: Using an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease. Thrombosis recurrence and major bleeding were prospectively analyzed using Kaplan-Meier method and compared using a marginal Cox's regression model. RESULTS: As of June 2022, 94 (14 %) of the 662 TAPS patients were not anticoagulated; and 93 of them were matched with 181 anticoagulated TAPS patients (median follow-up 5 years [interquartile range 3 to 8]). The 5-year thrombosis recurrence and major bleeding rates were 12 % versus 10 %, and 6 % versus 7 %, respectively (hazard ratio [HR] 1.38, 95 % confidence interval [CI] 0.53 to 3.56, p = 0.50 and HR 0.53; 95 % CI 0.15 to 1.86; p = 0.32, respectively). Non-anticoagulated patients were more likely to receive antiplatelet therapy (p < 0.001), and less likely to have more than one previous thrombosis (p < 0.001) and lupus anticoagulant positivity (p = 0.01). CONCLUSION: Fourteen percent of the TAPS patients were not anticoagulated at recruitment. Their recurrent thrombosis risk did not differ compared to matched anticoagulated TAPS patients, supporting the pressing need for risk-stratified secondary thrombosis prevention trials in APS investigating strategies other than anticoagulation.

A genome-wide association study suggests new susceptibility loci for primary antiphospholipid syndrome.

Objectives: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS. Methods: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases. Results: We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near HLA-DRA and in STAT4 with a genome-wide level of significance. 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele in the HLA class II locus is associated with overexpression of HLA-DRB6 , HLA-DRB9 , HLA-DPB2 , HLA-DQA2 and HLA-DQB2 , and is independent of the association between PAPS and HLA-DRB1*1302 . Functional analyses highlighted immune and nervous system related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren's syndrome, suggesting colocalized causal variations close to STAT4 , TNPO3 , and BLK . Conclusions: This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.

COVID-19 coagulopathy and antiphospholipid syndrome

The presence of thrombotic events in COVID-19 patients has been described since the beginning of the pandemic. This association has been confirmed in most of the reported studies. Autopsy reports have shown that most thromboses are located in the lung, although they have also been observed in other organs such as the skin and kidneys. SARS-CoV2 infection induces a generalized prothrombotic state, which is attributed to a combination of factors such as hypoxia, excess cellular apoptosis, and mainly to overactivation of the immune system. Among immune-mediated prothrombotic situations, antiphospholipid syndrome (APS) stands out. Recurrent thrombotic events are observed in APS in the presence of antiphospholipid antibodies (aPL). There are numerous studies that report high prevalence of aPL in patients with COVID-19 infection. However, the results show discrepancies in the data on the prevalence of aPL, and its role in the pathogenesis of thrombosis in these patients. This could be due to the heterogeneity of the detection procedures for aPL or to transient elevations of non-pathogenic aPL levels in the context of infection. In this review we try to clarify the role of aPL in COVID-19 infection, and attempt to answer the question of whether it is a coagulopathy of its own, or secondary to APS.

La presencia de eventos trombóticos en los pacientes con COVID-19 se describió desde el inicio de la pandemia, asociación que ha sido confirmada en la mayoría de los estudios reportados. Los informes de necropsias han puesto de manifiesto que la mayoría de las trombosis se localiza en el pulmón, aunque también se han observado en otros órganos, como la piel y los riñones. La infección por SARS-CoV-2 induce un estado protrombótico generalizado que se atribuye a una conjunción de factores como la hipoxia, el exceso de apoptosis celular y, sobre todo, una hiperactivación del sistema inmune. Entre las situaciones protrombóticas inmunomediadas destaca el síndrome antifosfolipídico, en el cual se observan eventos trombóticos de repetición en presencia de anticuerpos antifosfolipídicos (AAF). Existen numerosos estudios que reportan una elevada prevalencia de AAF en los pacientes con infección por la COVID-19; sin embargo, los resultados muestran discordancias en los datos de prevalencia de AAF y su rol en la patogenia sobre la trombosis en estos pacientes, lo que que podría deberse a la heterogeneidad de los procedimientos de detección de los AAF o a elevaciones transitorias de los niveles de AAF no patogénicos en el contexto de la infección. En esta revisión se busca aclarar el papel de los AAF en la infección por COVID-19, intentando responder a la pregunta de si se trata de una coagulopatía propia o es secundaria a un síndrome antifosfolipídico.