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10 pages, 1088 KiB

Open AccessArticle

The Predictive Value of the aCL and Anti-β2GPI at the Time of Acute Deep Vein Thrombosis—A Two-Year Prospective Study

by Katja Perdan-Pirkmajer, Polona Žigon, Anja Boc, Eva Podovšovnik, Saša Čučnik, Alenka Mavri, Žiga Rotar and Aleš Ambrožič

Biomedicines 2021, 9(8), 901; https://doi.org/10.3390/biomedicines9080901 - 27 Jul 2021

Cited by 2 | Viewed by 1641

Abstract

Antiphospholipid syndrome (APS) is an important cause of deep vein thrombosis (DVT). According to current APS classification criteria, APS cannot be confirmed until 24 weeks after DVT. This time frame results in frequent discontinuation of anticoagulant treatment before APS is diagnosed. Therefore, the [...] Read more.

Antiphospholipid syndrome (APS) is an important cause of deep vein thrombosis (DVT). According to current APS classification criteria, APS cannot be confirmed until 24 weeks after DVT. This time frame results in frequent discontinuation of anticoagulant treatment before APS is diagnosed. Therefore, the aim of our study was to evaluate the potential predictive value of anticardiolipin (aCL) and anti-β2glycoprotein I (anti-β2GPI) before discontinuation of anticoagulation therapy. Patients with newly diagnosed DVT were included into a 24-month prospective study. All patients received anticoagulant therapy. aCL and anti-β2GPI were determined at inclusion and every four weeks for the first 24 weeks and then one and two years after inclusion. APS was confirmed in 24/221 (10.9%) patients. At the time of acute DVT 20/24 (83.3%), APS patients had positive aCL and/or anti-β2GPI. Two patients had low aCL levels and two were negative at the time of acute DVT but later met APS criteria due to lupus anticoagulant (LA). Our data indicate that negative aCL and/or anti-β2GPI at the time of acute DVT make further aPL testing unnecessary; however, LA should be determined after discontinuation of anticoagulant therapy. Positive aCL and/or anti-β2GPI at the time of acute DVT have a strong positive predictive value for APS and may support therapeutic decisions. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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16 pages, 4434 KiB

Open AccessArticle

Anti-Phospholipid Antibodies and COVID-19 Thrombosis: A Co-Star, Not a Supporting Actor

by Francisco Javier Gil-Etayo, Sara Garcinuño, Antonio Lalueza, Raquel Díaz-Simón, Ana García-Reyne, Daniel Enrique Pleguezuelo, Oscar Cabrera-Marante, Edgard Alfonso Rodriguez-Frias, Alfredo Perez-Rivilla, Manuel Serrano and Antonio Serrano

Biomedicines 2021, 9(8), 899; https://doi.org/10.3390/biomedicines9080899 - 27 Jul 2021

Cited by 11 | Viewed by 2474

Abstract

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL [...] Read more.

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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9 pages, 412 KiB

Open AccessArticle

Low Preconception Complement Levels Are Associated with Adverse Pregnancy Outcomes in a Multicenter Study of 260 Pregnancies in 197 Women with Antiphospholipid Syndrome or Carriers of Antiphospholipid Antibodies

by Cecilia Nalli, Daniele Lini, Laura Andreoli, Francesca Crisafulli, Micaela Fredi, Maria Grazia Lazzaroni, Viktoria Bitsadze, Antonia Calligaro, Valentina Canti, Roberto Caporali, Francesco Carubbi, Cecilia Beatrice Chighizola, Paola Conigliaro, Fabrizio Conti, Caterina De Carolis, Teresa Del Ross, Maria Favaro, Maria Gerosa, Annamaria Iuliano, Jamilya Khizroeva, Alexander Makatsariya, Pier Luigi Meroni, Marta Mosca, Melissa Padovan, Roberto Perricone, Patrizia Rovere-Querini, Gian Domenico Sebastiani, Chiara Tani, Marta Tonello, Simona Truglia, Dina Zucchi, Franco Franceschini and Angela Tincani Show full author list Hide full author list

Biomedicines 2021, 9(6), 671; https://doi.org/10.3390/biomedicines9060671 - 11 Jun 2021

Cited by 19 | Viewed by 2801

Abstract

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be [...] Read more.

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers’ pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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13 pages, 1776 KiB

Open AccessArticle

Validation of the Particle-Based Multi-Analyte Technology for Detection of Anti-PhosphatidylSerine/Prothrombin Antibodies

by Massimo Radin, Irene Cecchi, Silvia Grazietta Foddai, Elena Rubini, Alice Barinotti, Carlos Ramirez, Andrea Seaman, Dario Roccatello, Michael Mahler and Savino Sciascia

Biomedicines 2020, 8(12), 622; https://doi.org/10.3390/biomedicines8120622 - 17 Dec 2020

Cited by 5 | Viewed by 2430

Abstract

Among “extra-criteria” antiphospholipid (aPL) antibodies, anti-phosphatidylserine/prothrombin (aPS/PT) antibodies, are considered a part of risk assessment strategies when investigating patients suspected of having antiphospholipid syndrome (APS). aPL detection is currently performed by solid-phase assays to identify anti-cardiolipin (aCL), anti-β2glycoprotein I (aβ2GPI) and aPS/PT antibodies, [...] Read more.

Among “extra-criteria” antiphospholipid (aPL) antibodies, anti-phosphatidylserine/prothrombin (aPS/PT) antibodies, are considered a part of risk assessment strategies when investigating patients suspected of having antiphospholipid syndrome (APS). aPL detection is currently performed by solid-phase assays to identify anti-cardiolipin (aCL), anti-β2glycoprotein I (aβ2GPI) and aPS/PT antibodies, but new techniques are emerging. Among these, particle-based multi-analyte technology (PMAT), which allows the full automation and simultaneous digital detection of autoantibodies and proteins, including IgG, IgA and IgM isotypes of aCL, aβ2GPI and aPS/PT. The aim of this study was to investigate the agreement of aPS/PT testing between enzyme-linked immunosorbent assay (ELISA) and the PMAT platform. A total of 94 patients were enrolled in the study, including 71 patients with confirmed APS and 23 “aPL carriers”. aPS/PT IgG showed a moderate binomial agreement between ELISA and PMAT (k = 0.57, 95% CI 0.45–0.75), and aPS/PT IgM showed a moderate agreement (k = 0.60, 95% CI 0.45–0.75). Moreover, when considering the continuous agreement, both aPS/PT IgG and IgM showed a statistically significant correlation between ELISA and PMAT (Spearman’s correlation = 0.69, p < 0.001 and 0.72, p < 0.001, respectively). This study demonstrates that PMAT technology is a reliable method for aPS/PT IgG and IgM testing when compared to the available commercial ELISA kit. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 1218 KiB

Open AccessArticle

17β-Estradiol Promotes Proinflammatory and Procoagulatory Phenotype of Innate Immune Cells in the Presence of Antiphospholipid Antibodies

by Gayane Manukyan, Anush Martirosyan, Ludek Slavik, Jana Ulehlova, Martin Dihel, Tomas Papajik and Eva Kriegova

Biomedicines 2020, 8(6), 162; https://doi.org/10.3390/biomedicines8060162 - 15 Jun 2020

Cited by 3 | Viewed by 2720

Abstract

Antiphospholipid syndrome (APS) is the most common cause of acquired thrombophilia and recurrent spontaneous miscarriages associated with extended persistence of antiphospholipid antibodies (aPL). How circulating aPL and high-17β-estradiol (E2) environment contribute to the pregnancy complications in APS is poorly defined. Therefore, we aimed [...] Read more.

Antiphospholipid syndrome (APS) is the most common cause of acquired thrombophilia and recurrent spontaneous miscarriages associated with extended persistence of antiphospholipid antibodies (aPL). How circulating aPL and high-17β-estradiol (E2) environment contribute to the pregnancy complications in APS is poorly defined. Therefore, we aimed to analyse whether E2 could be responsible for the immune cell hyperactivation in aPL- positive (lupus anticoagulant, anti-cardiolipin, anti-β2-glycoprotein) in women. For this, peripheral blood mononuclear cells (PBMCs) from 14 aPL- positive and 13 aPL- negative women were cultured in the presence or absence of E2, LPS or E2+LPS and cell immunophenotype and cytokine release were analysed. In the aPL+ group, E2 presence markedly increased the percentage of NK cells positive for CD69 (p < 0.05), monocytes positive for tissue factor (TF, CD142) (p < 0.05), and B cells expressing PD-L1 (p < 0.05), as well as the elevated production of IL-1β comparing to aPL- women (p < 0.01). Regardless of aPL positivity, E2 augmented the procoagulatory response elicited by LPS in monocytes. Our findings show the ability of E2 to promote proinflammatory and procoagulatory phenotype of innate immune cells in individuals with aPL positivity. Our data highlights the significant impact of female hormones on the activation of immune cells in the presence of aPL. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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Review

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12 pages, 810 KiB

Open AccessReview

Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?

by Riccardo Tomasello, Giulio Giordano, Francesco Romano, Federica Vaccarino, Sergio Siragusa, Alessandro Lucchesi and Mariasanta Napolitano

Biomedicines 2021, 9(9), 1170; https://doi.org/10.3390/biomedicines9091170 - 06 Sep 2021

Cited by 13 | Viewed by 3886

Abstract

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same [...] Read more.

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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10 pages, 396 KiB

Open AccessReview

Diagnostic Challenges on the Laboratory Detection of Lupus Anticoagulant

by Armando Tripodi

Biomedicines 2021, 9(7), 844; https://doi.org/10.3390/biomedicines9070844 - 20 Jul 2021

Cited by 8 | Viewed by 5805

Abstract

Lupus anticoagulant (LA) is one of the three laboratory parameters (the others being antibodies to either cardiolipin or β2-glycoprotein I) which defines the rare but potentially devastating condition known as antiphospholipid syndrome (APS). Testing for LA is a challenging task for the clinical [...] Read more.

Lupus anticoagulant (LA) is one of the three laboratory parameters (the others being antibodies to either cardiolipin or β2-glycoprotein I) which defines the rare but potentially devastating condition known as antiphospholipid syndrome (APS). Testing for LA is a challenging task for the clinical laboratory because specific tests for its detection are not available. However, proper LA detection is paramount for patients’ management, as its persistent positivity in the presence of (previous or current) thrombotic events, candidate for long term anticoagulation. Guidelines for LA detection have been established and updated over the last two decades. Implementation of these guidelines across laboratories and participation to external quality assessment schemes are required to help standardize the diagnostic procedures and help clinicians for appropriate management of APS. This article aims to review the current state of the art and the challenges that clinical laboratories incur in the detection of LA. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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15 pages, 1212 KiB

Open AccessReview

Current Promising Biomarkers and Methods in the Diagnostics of Antiphospholipid Syndrome: A Review

by Pavla Bradacova, Ludek Slavik, Jana Ulehlova, Adela Skoumalova, Jana Ullrychova, Jana Prochazkova, Antonin Hlusi, Gayane Manukyan and Eva Kriegova

Biomedicines 2021, 9(2), 166; https://doi.org/10.3390/biomedicines9020166 - 08 Feb 2021

Cited by 18 | Viewed by 3497

Abstract

Antiphospholipid syndrome (APS) is a hypercoagulation condition associated with the incidence of heterogenic antiphospholipid antibodies (aPLs), which non-specifically affect hemostasis processes. APS is clinically manifested by recurrent arterial and venous thromboses and reproduction losses. The aPL antibodies, which may induce clinical manifestations of [...] Read more.

Antiphospholipid syndrome (APS) is a hypercoagulation condition associated with the incidence of heterogenic antiphospholipid antibodies (aPLs), which non-specifically affect hemostasis processes. APS is clinically manifested by recurrent arterial and venous thromboses and reproduction losses. The aPL antibodies, which may induce clinical manifestations of APS, include criteria antibodies anti-cardiolipin, anti-β2-glycoprotein-I, and lupus anticoagulant, but also non-criteria antibodies, for example anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-annexin V, and many others. APS occurs mostly in patients of younger and middle age, most frequently in females. Laboratory diagnostics of APS are quite difficult, as they include a wide spectrum of examining methods, which are based on various principles of detection and are performed using various laboratory techniques. The objective of the review is to describe the current state of potentially examined biomarkers and methods in APS diagnostics. The aforementioned biomarkers are lupus anticoagulant, anti-β2-glycoprotein-I, anti-cardiolipin, anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-β2-glycoprotein-I IgA, anti-cardiolipin IgA, anti-annexin V and II, anti-prothrombin, anti-cardiolipin/vimentin, anti-protein S/protein C, and antibodies against phospholipid antigens for whose diagnostics we may use some of the methods established for a long time and some of the modern methods—the coagulation method for the determination of lupus anticoagulant (LA), enzyme-linked imunosorbent assay (ELISA), chemiluminescence analysis (CLIA), multiplex fluorescence flow immunoassay (MFFIA), fluorescence enzyme immunoassay (EliA), line immunoassay (LIA), multiline dot assay (MLDA), and thin-layer chromatography (TLC). Conclusion: Antibodies against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, cardiolipin/vimentin complex, and annexin V are currently the most studied new markers. However, these assays have not been standardized until now, both from the laboratory and clinical point of view. In this review we summarize the evidence of the most studied aPL markers and their potential clinical significance in seronegative APS (SN-APS). Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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21 pages, 783 KiB

Open AccessReview

Immunosuppressive Treatment in Antiphospholipid Syndrome: Is It Worth It?

by Ilaria Mormile, Francescopaolo Granata, Alessandra Punziano, Amato de Paulis and Francesca Wanda Rossi

Biomedicines 2021, 9(2), 132; https://doi.org/10.3390/biomedicines9020132 - 01 Feb 2021

Cited by 12 | Viewed by 5001

Abstract

The antiphospholipid syndrome (APS) is characterized by the development of venous and/or arterial thrombosis and pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of APS occurring in about 1% of cases. Lifelong anticoagulation with [...] Read more.

The antiphospholipid syndrome (APS) is characterized by the development of venous and/or arterial thrombosis and pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of APS occurring in about 1% of cases. Lifelong anticoagulation with vitamin K antagonists remains the cornerstone of the therapy for thrombotic APS, but frequently the use of anticoagulation may be problematic due to the increased risk of bleeding, drug interactions, or comorbidities. Immunosuppressant drugs are widely used to treat several autoimmune conditions, in which their safety and effectiveness have been largely demonstrated. Similar evidence in the treatment of primary APS is limited to case reports or case series, and studies on a large scale lack. Immunomodulatory drugs may be an emerging tool in managing such particular situations, like refractory obstetrical complications, CAPS, or so-called APS non-criteria manifestations. In addition, immunomodulatory drugs may be useful in patients experiencing recurrent thromboembolic events despite optimized anticoagulant therapy. We did a comprehensive review of literature analyzing the possible role of immunomodulation in primary APS to provide a broad overview of potentially safe and effective target treatments for managing this devastating disease. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 1037 KiB

Open AccessReview

Risk Assessment and Antithrombotic Strategies in Antiphospholipid Antibody Carriers

by Ilenia Calcaterra, Pasquale Ambrosino, Nicoletta Vitelli, Roberta Lupoli, Roberta Clara Orsini, Martina Chiurazzi, Mauro Maniscalco and Matteo Nicola Dario Di Minno

Biomedicines 2021, 9(2), 122; https://doi.org/10.3390/biomedicines9020122 - 27 Jan 2021

Cited by 6 | Viewed by 3434

Abstract

Antiphospholipid antibodies (aPL) are a cluster of autoantibodies directed against plasma proteins with affinity for membrane phospholipids. The most frequently tested aPL are lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-β2GPI). aPL play a key pathogenic role in the development [...] Read more.

Antiphospholipid antibodies (aPL) are a cluster of autoantibodies directed against plasma proteins with affinity for membrane phospholipids. The most frequently tested aPL are lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-β2GPI). aPL play a key pathogenic role in the development of the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by recurrent thrombotic and/or pregnancy complications in patients with persistent aPL. However, aPL positivity is occasionally documented in patients with no previous history of thrombotic or pregnancy morbidity. LA activity, multiple aPL positivity, high-titer aPL, and a concomitant systemic autoimmune disease are recognized risk factors for future thrombotic events in asymptomatic carriers. Moreover, an accelerated atherosclerosis with increased cardiovascular (CV) risk has also been associated with aPL positivity, thus exposing aPL carriers to fatal complications and chronic disability requiring cardiac rehabilitation. Overall, an accurate risk stratification is recommended for aPL-positive subjects in order to prevent both venous and arterial thrombotic complications. In this review, we provide an overview of the main antithrombotic and risk assessment strategies in aPL carriers. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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17 pages, 378 KiB

Open AccessReview

Management of Antiphospholipid Syndrome

by Amine Ghembaza and David Saadoun

Biomedicines 2020, 8(11), 508; https://doi.org/10.3390/biomedicines8110508 - 17 Nov 2020

Cited by 17 | Viewed by 6096

Abstract

Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation [...] Read more.

Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected. As APS is a heterogeneous condition, its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors. Although literature data are conflicting regarding primary prophylaxis, there is some evidence indicating that antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile. In patients with thrombotic APS, current evidence-based guidelines recommend lifelong vitamin K antagonists (VKAs), preferably warfarin. The optimal intensity of anticoagulation following arterial thrombosis remains controversial. Arterial thrombosis should be treated either with high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0–3.0). It is recommended to avoid direct oral anticoagulants (DOACs) in patients with high-risk APS, mainly those with triple-positive PL and previous arterial events. They would only be used exceptionally in selected patients with low-risk venous thromboembolism (VTE). In low-risk VTE patients currently treated with a DOAC due to warfarin intolerance or a previous unstable International Normalized Ratio on warfarin, the decision of continuing DOACs would be taken in carefully selected patients. In women with obstetric APS, the combination therapy with LDA plus heparin remains the conventional strategy. Full article

(This article belongs to the Special Issue Antiphospholipid Syndrome: From Pathophysiology to Novel Therapeutic Approaches)

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