Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17-21, 2021. The conference, now held annually, highlighted cutting-edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person. An added feature of the program is that talks streamed at the designated times will then be available on-line for asynchronous viewing. The program included 77 State of the Art (SOA) talks, thematically grouped in 28 sessions, given by internationally recognized leaders in the field. The SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. The topics, across the main scientific themes of the congress, include Arterial Thromboembolism, Coagulation and Natural Anticoagulants, COVID-19 and Coagulation, Diagnostics and Omics, Fibrinogen, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostasis in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Angiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the congress.

Plasma from patients with pulmonary embolism show aggregates that reduce after anticoagulation.

BACKGROUND: Microclots, a term also used for amyloid fibrin(ogen) particles and henceforth named aggregates, have recently been reported in the plasma of patients with COVID-19 and long COVID. These aggregates have been implicated in the thrombotic complications of these diseases. METHODS: Plasma samples from 35 patients with acute pulmonary embolism were collected and analysed by laser scanning confocal microscopy and scanning electron microscopy before and after clotting. RESULTS: Here we confirm the presence of aggregates and show that they also occur in the plasma of patients with pulmonary embolism, both before and after clotting. Aggregates vary in size and consist of fibrin and platelets. We show that treatment with low-molecular weight heparin reduces aggregates in the samples of patients with pulmonary embolism. Double centrifugation of plasma does not eliminate the aggregates. CONCLUSIONS: These data corroborate the existence of microclots or aggregates in diseases associated with venous thromboembolism. Important questions are raised regarding their pathophysiological relevance and further studies are warranted to investigate whether they represent cause or consequence of clinical thrombosis.

When blood turns from liquid to solid, a protein called fibrin and cells called platelets aggregate to form a blood clot. Small aggregates have been found in the blood of people with COVID-19 and long COVID. Here, we show that small aggregates also occur in the blood of patients with pulmonary embolism, a disorder in which blood clots are trapped in an artery in the lung, preventing blood flow. We confirm that aggregates consist of fibrin and platelets, and show that the number of aggregates is lower when patients are treated with blood thinning drugs. These results suggest other disorders of the blood should also be investigated to see whether aggregates are present and whether they have an impact on the outcome for the patient. This could help us understand the cause of diseases associated with blood clotting, which might offer new approaches for diagnosis and treatment.

Thromboprophylaxis in hospitalized COVID-19 patients: the efficacy and safety of the approved hospital protocol.

Introduction: Prothrombotic coagulopathy in COVID-19 has led to a strong recommendation for thromboprophylaxis in all hospitalized patients, although there are large differences in the dosage regimens among hospitals and their outcomes remain uncertain. Objectives: We aimed to determine the incidence of thrombotic events and bleeding in patients with COVID-19 using the approved local thromboprophylaxis protocol. Patients and methods: We adapted a self-developed pharmacological thromboprophylaxis protocol based on clinical and laboratory risk assessment of thrombosis in 350 consecutive patients (median age, 67 years) with confirmed COVID-19, treated in designated wards at a single center in Kraków, Poland from October 10, 2020, to April 30, 2021. We recorded in-hospital venous and arterial thromboembolic events, major or clinically relevant bleeding, and deaths along with other complications related to heparin administration. Results: Thromboprophylaxis with low-molecular-weight heparin was administered in 99.7% of patients, 57 (16%) were treated in the intensive care unit. As many as 92% of patients followed the protocol for more than 85% of hospitalization time. Thromboembolic events occurred in 16 patients (4.4%): venous thromboembolism (n = 4; 1.1%), ischemic stroke (n = 4; 1.1%), and myocardial infarction (n = 8; 2.2%). Hemorrhagic complications were observed in 31 patients (9%), including fatal bleeds (n = 3; 0.9%). The overall mortality was 13.4%. The prophylactic, intermediate, and therapeutic anticoagulation preventive strategies with heparin were not related to any of the outcomes. Conclusions: The thromboprophylaxis protocol approved in our institution was associated with a relatively low risk of thromboembolism and bleeding, which provides additional evidence supporting the adoption of institutional strategies to improve outcomes in hospitalized patients with COVID-19.

Current treatment challenges in the COVID-19 pandemic.

Infection with SARS-CoV-2, responsible for COVID-19, has spread all over the world since the beginning of 2020. Healthcare providers and researchers have been overwhelmed not only by the rapid diffusion of the disease resulting in a pandemic with more than 4 million cases of death, but also by the lack of therapeutic options. After more than 1 year, the knowledge on COVID-19 has increased thanks to the enormous effort of the scientific community. To date, some algorithms of management have been adopted. While asymptomatic or mildly symptomatic patients should receive only a symptom-based treatment and clinical monitoring when necessary, inpatients could be candidates for antiviral treatment due to fully symptomatic disease. Corticosteroid treatment should be limited to patients with severe disease, particularly those with respiratory failure or acute respiratory distress syndrome. Since the main clinical features of COVID-19 are hypoxemia and dyspnea, oxygen therapy remains the cornerstone of managing more severe cases. In this context, the first-line approach should be represented by low-flow oxygen delivery via a nasal cannula or, more frequently, via a face mask with a known fraction of inspired oxygen. When low-flow oxygen fails to significantly improve oxygen saturation, oxygen therapy using a high-flow nasal cannula is recommended. The current challenges in the treatment of COVID-19 include the need to define the role of convalescent plasma and monoclonal antibodies as well as to identify the optimal target and time for anticoagulation. In this review, we highlight the main aspects of these challenges in light of recent updates.

Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients.

BACKGROUND: Emerging data indicates that extracellular traps (ETs), structures formed by various immune cell types, may contribute to the pathology of noninfectious inflammatory diseases. Histone hypercitrullination is an important step in ETs formation and citrullinated histone H3 (H3cit) is considered a novel and specific biomarker of that process. In the present study we have evaluated circulating H3cit in stable asthmatics and investigated its relationship with asthma severity, pulmonary function and selected blood and bronchoalveolar lavage (BAL) biomarkers. METHODS: In 60 white adult stable asthmatics and 50 well-matched controls we measured serum levels of H3cit. In asthmatics we also performed bronchoscopy with BAL. We analyzed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A and interferon γ. For statistical analysis, Mann-Whitney U-test, χ2 test, one-way ANCOVA, ROC curve analysis and univariate linear regression were applied. Independent determinants of H3cit were established in a multiple linear regression model. RESULTS: Asthma was characterized by elevated circulating H3cit (17.49 [11.25-22.58] vs. 13.66 [8.66-18.87] ng/ml, p = 0.03). In asthmatics positive associations were demonstrated between serum H3cit and lung function variables, including total lung capacity (TLC) (ß = 0.37 [95% CI 0.24-0.50]) and residual volume (ß = 0.38 [95% CI 0.25-0.51]). H3cit was increased in asthma patients receiving systemic steroids (p = 0.02), as well as in subjects with BAL eosinophilia above 144 cells/ml (p = 0.02). In asthmatics, but not in controls, circulating H3cit correlated well with number of neutrophils (ß = 0.31 [95% CI 0.19-0.44]) and monocytes (ß = 0.42 [95% CI 0.29-0.55]) in peripheral blood. Furthermore, BAL macrophages, BAL neutrophils, TLC, high-sensitivity C-reactive protein, Il-12p70 and bronchial obstruction degree were independent determinants of H3cit in a multivariate linear regression model. CONCLUSIONS: Asthma is characterized by increased circulating H3cit likely related to the enhanced lung ETs formation. Inhibition of ETs might be a therapeutic option in selected asthma phenotypes, such as neutrophilic asthma.

Guidance for anticoagulation management in venous thromboembolism during the coronavirus disease 2019 pandemic in Poland: an expert opinion of the Section on Pulmonary Circulation of the Polish Cardiac Society.

The coronavirus disease 2019 (COVID-19) pandemic affects anticoagulation not only in those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also in most patients who require daily anticoagulant therapy and are facing substantial limitations in medical care these days. Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has frequently been reported in patients with COVID-19, but its management is still challenging due to the complexity between antithrombotic therapy and hematological alterations. In the era of COVID-19 pandemic, it is highly recommended for patients who require chronic anticoagulation to continue therapy to prevent thromboembolic events. To avoid regular and frequent blood tests and unnecessary exposure to SARS-CoV-2 during contacts with medical personnel, direct oral anticoagulants should be strongly preferred whenever possible. Current evidence is insufficient to recommend routine pharmacological antithrombotic prophylaxis in all hospitalized patients with COVID-19. In patients with COVID-19 who are suspected of VTE or in whom the diagnosis is confirmed, parenteral therapy with low-molecular-weight heparin should be initiated in the absence of contraindications. If heparin-induced thrombocytopenia is suspected, nonheparin anticoagulants should be used such as bivalirudin or fondaparinux. In case of confirmed acute pulmonary embolism, treatment should be guided by risk stratification as defined in the current guidelines.