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This document is an editorial celebrating the 50th anniversary of Seminars in Thrombosis and Hemostasis (STH), a medical journal that first published in 1974. The editorial discusses the various celebratory issues that have been published over the years, which contain historical content related to the fields of thrombosis and hemostasis. The document also mentions the republishing of highly cited and downloaded papers from STH, along with accompanying commentaries from experts in the respective fields. Additionally, the document provides a list of the 50 most highly downloaded papers from STH between 2014 and 2023. [Extracted from the article]

This document is a list of articles published in the journal Seminars in Thrombosis and Hemostasis. The articles cover a wide range of topics related to platelets, coagulation, and thrombosis. Some of the topics include the role of platelets in cancer, the measurement of microparticles, risk factors for venous thromboembolism, and the use of statins in COVID-19 patients. The articles provide valuable information for researchers and healthcare professionals interested in these areas of study. [Extracted from the article]

The latest issue of Seminars in Thrombosis and Hemostasis (STH) is a compilation of articles covering various topics related to thrombosis and bleeding. It includes reviews on neonates with intrauterine growth restriction, pediatric presentations of the antiphospholipid syndrome, genetic variations in tissue factor-dependent disease, heterozygous factor XIII deficiency, and the use of global hemostasis assays in patients with myeloproliferative neoplasms. The document also features reviews on the role of CD36 in platelet activation, laser-induced blood coagulation in surgery, detecting blood clots in ECMO circuits, post-COVID venous thrombosis, and the effects of SARS-CoV-2 spike protein variants on platelets. Commentaries on various topics and the republishing of historical papers are also included. [Extracted from the article]

Semin Thromb Hemost 2020;46(3):379-3824Thachil J, Srivastava A. SARS-2 coronavirus-associated hemostatic lung abnormality in COVID-19: is it pulmonary thrombosis or pulmonary embolism? Semin Thromb Hemost 2020;46(7):789-79538Horowitz NA, Brenner B. thrombosis and hemostasis issues in cancer patients with COVID-19. 2021, 47, 05, 467 - 476 52 Favaloro E. J., Lippi G. Maintaining hemostasis and preventing thrombosis in coronavirus disease 2019 (COVID-19)-part I. Semin Thromb Hemost. Semin Thromb Hemost 2020;46(7):796-8038Fernández-Capitán C, Barba R, Díaz-Pedroche MDC, Sigüenza P, Demelo-Rodriguez P, Siniscalchi C, Pedrajas JM, Farfán-Sedano AI, Olivera PE, Gómez-Cuervo C, Llamas P, Villares P, Sanchez O, López-Reyes R, Catella J, Bikdeli B, Weinberg I, Tafur AJ, Jiménez D, Monreal M. presenting characteristics, treatment patterns, and outcomes among patients with venous thromboembolism during hospitalization for COVID-19. [Extracted from the article]

Semin Thromb Hemost 2021; 47 (04): 333-337 36 Favaloro E J, Lippi G. Maintaining hemostasis and preventing thrombosis in coronavirus disease 2019 (COVID-19)-Part III. Semin Thromb Hemost 2022;48(1):19-308Favaloro EJ, Henry BM, Lippi G. Increased VWF and decreased ADAMTS-13 in COVID-19: creating a milieu for (micro)thrombosis. Semin Thromb Hemost 2022; 48 (01): 19-30 8 Favaloro E J, Henry B M, Lippi G. Increased VWF and decreased ADAMTS-13 in COVID-19: creating a milieu for (micro)thrombosis. Semin Thromb Hemost 2022; 48 (01): 3-7 37 Favaloro E J, Pasalic L, Lippi G. Maintaining hemostasis and preventing thrombosis in coronavirus disease 2019 (COVID-19)-Part IV. [Extracted from the article]

The article introduces various papers published within the issue, including one on thrombosis as a major contributor to global disease burden, another on venous thromboembolism (VTE) in tropical Australia and in indigenous Australians and a paper on antiphospholipid syndrome (APS).

Russell Viper Venom (RVV) is widely used as a diagnostic test for antiphospholipid syndrome (APS). But the history of how this venom came to be discovered is well known. Dr Patrick Russell is responsible for the identification of the venom during his work on snake bites in India while Dr Robert Macfarlane used it to staunch bleeding in persons with haemophilia. The ability to directly activate factor X led RVV to the laboratory diagnosis of APS. More recently, it has come back to clinical world with a potential for an engineered factor X activator from RVV to be used in the treatment of haemophilia. [ABSTRACT FROM AUTHOR]

Unprovoked (or provoked by mild risk factors) venous thromboembolism (VTE) in young patients, VTE in uncommon sites, or cases of unexplained VTE recurrence may be positive for antiphospholipid antibodies (aPL) and thus may be diagnosed with antiphospholipid syndrome (APS). The evaluation of aPL is standardized using immunological tests for anticardiolipin and anti-β2-glycoprotein I. The determination of functional antibodies (lupus anticoagulant) is less standardized, especially in patients on anticoagulant treatment. Patients positive for all the three tests are at high risk of recurrence, which, in turn, might lead to chronic obstruction of pulmonary vessels (chronic thromboembolic pulmonary hypertension). Randomized clinical trials have shown that triple-positive patients should be treated with vitamin K antagonists maintaining an international normalized ratio between 2 and 3. Whether patients with VTE and incomplete aPL profile can be treated with direct oral anticoagulants should be further investigated. [ABSTRACT FROM AUTHOR]

Semin Thromb Hemost 2021; 47 (03): 229-237 5 Selvadurai M V, Favaloro E J, Chen V M. Mechanisms of thrombosis in heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia. Welcome to the latest issue of I Seminars in Thrombosis and Hemostasis (STH) i published under the "banner" of "Editorial Compilation", with this being the thirteenth such issue (Table 1). Semin Thromb Hemost 2023; 49 (05): 553-557 18 Favaloro E J, Pasalic L, Lippi G. Maintaining hemostasis and preventing thrombosis in coronavirus disease 2019 (COVID-19) - Part IV. The authors propose that post-COVID-19 persistent platelet activation may explain why high-risk patients such as ICU patients could benefit from antiplatelet treatment regimens post-COVID-19 infection to mitigate their risk of developing thrombotic events after hospital discharge. [Extracted from the article]

The article presents the discussion on growing role of artificial intelligence in medicine, emphasizing its contributions to diagnosis, prognosis, and personalized treatment while acknowledging the irreplaceable value of human empathy in patient care. Topics include machine learning models for predicting thrombosis risk, the impact of COVID-19 on thromboembolism; and advances in diagnostic and treatment strategies for venous thromboembolism.

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. [ABSTRACT FROM AUTHOR]

Chorea is considered a nonthrombotic manifestation of the antiphospholipid syndrome, often preceding thrombotic events in children. It can be present in up to 5% of pediatric patients with antiphospholipid syndrome. Immunomodulatory treatment regimens seem to be successful in these patients, emphasizing the underlying immunological etiology. Corticosteroids are considered first-line treatment, but chorea tends to be therapy-resistant and guidelines about second-line therapy in children are solely based on small case studies. We present a case of a therapy-resistant chorea, successfully treated with rituximab. Furthermore, we give an overview of the existing literature concerning rituximab for the treatment of chorea in children. Our findings indicate that rituximab can be considered a safe option to treat antiphospholipid syndrome-related chorea in children. [ABSTRACT FROM AUTHOR]

Lupus anticoagulant (LA) is one of the three criteria antiphospholipid antibodies (aPLs) employed in classification, and by default diagnosis, of antiphospholipid syndrome (APS). Detection of LA is not via calibrated assays but is based on functional behavior of the antibodies in a medley of coagulation assays. A prolonged clotting time in a screening test is followed by demonstration of phospholipid dependence and inhibitory properties in confirmatory and mixing tests, respectively, which are modifications of the parent screening test. Complications arise because no single screening test is sensitive to every LA, and no test is specific for LA, because they are prone to interference by other causes of elevated clotting times. Several screening tests are available but the pairing of dilute Russell's viper venom time (dRVVT) with LA-sensitive activated partial thromboplastin time (aPTT) is widely used and recommended because it is proven to have good detection rates. Nonetheless, judicious use of other assays can improve diagnostic performance, such as dilute prothrombin time to find LA unreactive with dRVVT and aPTT, and the recently validated Taipan snake venom time with ecarin time confirmatory test that are unaffected by vitamin K antagonist and direct factor Xa inhibitor anticoagulation. Expert body guidelines and their updates have improved harmonization of laboratory practices, although some issues continue to attract debate, such as the place of mixing tests in the medley hierarchy, and areas of data manipulation such as assay cut-offs and ratio generation. This article reviews current practices and challenges in the laboratory detection of LA. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (aPL) comprise a panel of autoantibodies that reflect a potential prothrombotic risk in several autoimmune conditions, most notably antiphospholipid (antibody) syndrome (APS). aPL can be divided into those that form part of the laboratory criteria for APS, namely, lupus anticoagulant (LA), as well as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) of the immunoglobulin G and M classes, and those that form a group considered as "noncriteria antibodies." The noncriteria antibodies include, for example, antiphosphatidylserine antibodies (aPS), antiprothrombin antibodies (aPT), and antiphosphatidylserine/prothrombin complex antibodies (aPS/PT). COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of various aPL being present in COVID-19 patients. There have also been similarities drawn between some of the pathophysiological features of COVID-19 and APS, in particular, the most severe form, catastrophic APS (CAPS). In this review, we critically appraise the literature on aPL and COVID-19. This is a companion piece to a separate review focused on LA. In the current review, we primarily concentrate on the so-called solid phase identifiable aPL, such as aCL and aβ2GPI, but also reflect on noncriteria aPL. We conclude that aPL positivity may be a feature of COVID-19, at least in some patients, but in general, identified "solid-phase" aPL are of low titer and not able to be well-linked to the thrombotic aspects of COVID-19. Also, most publications did not assess for aPL persistence, and where persistence was checked, the findings appeared to represent transient aPL. Importantly, high-titer aPL or multiple aPL positivity (including double, triple) were in the minority of COVID-19 presentations, and thus discount any widespread presence of APS, including the most severe form CAPS, in COVID-19 patients. [ABSTRACT FROM AUTHOR]

If purified thrombin (1.0 IU/mL) is employed as the clotting trigger, fibrin network porosity may be affected by exogenous thrombin, which directly polymerizes fibrinogen in plasma, and additionally by endogenous thrombin stemming from a "positive feedback loop" action of the added thrombin. [1] This contribution was commissioned since thrombin is a topic of particular interest to our readership, and a relatively old publication on thrombin [2] kept appearing on our annual most popular lists, [3] indicating it was time to update the "thrombin story" for our readership. Welcome to the latest issue of I Seminars in Thrombosis and Hemostasis (STH) i published under the "banner" of "Editorial Compilation", this being the tenth such issue. Thrombin is a serine protease and a naturally derived enzyme that plays a key role in hemostasis by converting fibrinogen to fibrin and activating coagulation factor XIII whereby the fibrin clot is stabilized. [Extracted from the article]

There is a scarcity of high-quality randomized controlled trials (RCTs) comparing antithrombotic regimens for secondary prevention of arterial thrombosis (AT) in antiphospholipid syndrome (APS). We reviewed different antithrombotic regimens used for this purpose. We searched for studies on management of AT in APS on PubMed and Web of Science. Eleven studies (5 RCTs, 3 prospective, and 3 retrospective cohort studies) comparing different regimens and reporting outcomes specifically for patients with index AT events were identified. Treatments were vitamin K antagonists (VKA; 9 studies), non-VKA oral anticoagulant (NOAC; 3 studies), single antiplatelet therapy (SAPT; 7 studies), dual antiplatelet therapy (DAPT; 2 studies), and VKA combined with SAPT (4 studies). We performed a meta-analysis for the outcomes: recurrent AT, any (arterial or venous) recurrent thromboembolism, and major bleeding. Recurrent AT was reduced with VKA plus SAPT versus VKA (risk ratio [RR]: 0.43; 95% confidence interval [CI]: 0.22–0.85) and with DAPT versus SAPT (RR: 0.29; 95% CI: 0.09–0.99). Any recurrent thromboembolism was reduced with VKA plus SAPT versus VKA alone (RR: 0.41; 95% CI: 0.24–0.69) and versus SAPT alone (RR: 0.36; 95% CI: 0.13–0.96). There were no significant differences between other treatments for thromboembolism and for none of the comparisons regarding major bleeding. In a sensitivity analysis, excluding low-quality studies, VKA was more effective than NOAC to prevent recurrent AT (RR: 0.25; 95% CI: 0.07–0.93). Combined antithrombotic therapy might be more effective than single agents as secondary prophylaxis in APS with AT, and does not seem to compromise with safety, but the quality of evidence is generally low. NOACs should be avoided for patients with APS and AT. [ABSTRACT FROM AUTHOR]

Persistent serum positivity for antiphospholipid antibodies (aPL) is required to diagnose antiphospholipid syndrome (APS), an autoimmune disease characterized by recurrent vascular thrombosis and/or pregnancy morbidity. The current therapeutic management of patients with thrombotic APS aims at preventing recurrences and long-term complications by attenuating the procoagulant state. There is overall consensus to reserve moderate-intensity anticoagulation to aPL-positive patients with a previous venous thrombosis; the therapeutic options for those with a history of arterial event comprise antiplatelet agents and high-intensity anticoagulation. Unfortunately, thrombotic occurrencesmight occur despite adequate anticoagulation, carrying a significant burden of morbidity and mortality. The management of refractory thrombotic APS and catastrophic APS is still not clear, warranting the issue of recommendations. Vitamin-K antagonists are limited by significant side effects, and a careful weighting of risks and benefits should be performed to reserve the optimal treatment to each patient. To overcome these limitations, novel oral anticoagulants have been introduced in the market, but their efficacy in thrombotic APS has still to be unraveled. The poor safety profile and the scarce efficacy of drugs acting on the coagulation cascade explain why novel therapeutic approaches are currently under investigation, to identify pharmacological tools specifically counteracting aPL-mediated prothrombotic effects. [ABSTRACT FROM AUTHOR]

An introduction is presented in which authors discuss various topics published within the issue including one the pathogenesis of antiphospholipid syndrome (APS), another on the clinical and cohort studies of antiphospholipid antibody (aPL) and APS, and another one on the rarer clinical associations of aPL.

The antiphospholipid syndrome (APS) is an autoimmune condition characterized by vascular thromboses and/or pregnancy morbidity, and its diagnosis currently requires laboratory evidence of the presence of antiphospholipid antibodies (aPL). aPL are in turn identified using a large number of laboratory procedures based on one of two distinct test processes, namely solid-phase assays and liquid-phase assays. The former includes anticardiolipin antibodies and anti-?2 glycoprotein I antibodies, and the latter are centered on clot-based tests that are used to identify the so-called lupus anticoagulant. The current article provides an overview of the laboratory testing and identification of aPL, and in particular the limitations, standardization, and clinical utility of such testing. We also review preanalytical, analytical, and postanalytical issues that compromise the clinical utility of these tests. Finally, we provide a list of recommendations aimed to foster broader international cooperation to assist in the preparation of integrated guidelines, for both solid-phase and liquid-phase assays, and for laboratory testing, clinical ordering, and interpretation. [ABSTRACT FROM AUTHOR]

The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time, together with laboratory confirmation of the presence of antiphospholipid antibodies. The pathogenesis of catastrophic APS is not completely understood. The mortality rate was ~50% in the earliest published series, but recently it has clearly fallen by some 20% due to the use, as first-line therapies, of full anticoagulation, corticosteroids, plasma exchanges, and intravenous immunoglobulins. Cerebral involvement has been identified as the main cause of death, being present in one third of patients, and consisting mainly of stroke, cerebral hemorrhage and encephalopathy, followed by cardiac involvement and infection. The only identified prognostic factor for a higher mortality rate is the presence of systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Although many of the clinical features accompanying lupus anticoagulant positivity were documented in the early 1960s and many "non-lupus patients" were also published, it was not until the discovery of antibodies to cardiolipin in the 1980s that the existence and true ramifications of a distinct ANTIPHOSPHOLIPID SYNDROME was defined. A PRIMARY syndrome was in fact recognized in 1985 by the author while at the Hammersmith Hospital and comprised 25 patients who conformed to this new subset of disease, which has now overtaken lupus-associated (secondary) antiphospholipid syndromes in frequency. However, publication of this important milestone was in fact prevented, because of the purveying dogma at that time that "these patients were all suffering from 'lupus,'" which history has since proved to be incorrect. The syndrome was therefore only clearly defined AND published in 1988. Subsequently, in the following year, a new and more comprehensive multicenter series comprising 70 patients was documented (including the original 25 patients from 1985) as well as two smaller series by other units. The catastrophic variant of the syndrome with distinct triggering factors, clinical features, and a generally poor prognosis was then defined in 1992, with more than 300 patients with this devastating condition now summarized on the University of Barcelona online registry. The existence of a SERONEGATIVE syndrome has also been suggested, but whether this is related to the presence of undetectable antiphospholipid antibodies or perhaps represents a similar type of vasculopathy or endotheliopathy is unclear at the present time. This article documents a personal account of the events that took place in relation to the description of these syndromes. [ABSTRACT FROM AUTHOR]

The association of the lupus anticoagulant with thrombosis and recurrent pregnancy loss was first recognized over a 20-year period between the early 1960s and early 1980s. The introduction of the anticardiolipin test in 1983 and the recognition of its association with clinical features similar to the lupus anticoagulant led to an exponential growth of interest in this disorder. The belief that anticardiolipin antibodies and lupus anticoagulant belonged to the family of antiphospholipid antibodies led to the disorder being named the ANTIPHOSPHOLIPID SYNDROME (APS). Efforts by individual investigators to introduce criteria for classification of APS and to standardize anticardiolipin antibody and lupus anticoagulant tests were started in the mid-1980s to ensure more reliable recognition and treatment of affected patients. Another layer of complexity was introduced with recognition that many anticardiolipin antibody-positive sera also bound the antigen ? 2glycoprotein I. With increasingly sophisticated epidemiologic and prospective studies in the 1990s, more structured and better-documented criteria for APS were introduced in 1999 and modified in 2006. These criteria have been widely adopted. Whereas data supporting subclassification of APS into primary and secondary subgroups remain tenuous, a small percentage of patients do appear subject to clinical features termed the CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME. Introduction of classification criteria for APS has enabled more reliable prospective studies, the promise of better management, and more valid tests for recognition of the disorder. [ABSTRACT FROM AUTHOR]