| 1. |
- Ariens, Robert, et al.
(author)
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Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress
- 2020
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In: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - : Wiley. - 2475-0379. ; 4:5, s. 680-713
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Research review (peer-reviewed)abstract
- The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education.
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| 2. |
- Crow, Andrew R., et al.
(author)
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Treating murine inflammatory diseases with an anti-erythrocyte antibody
- 2019
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 11:506
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Journal article (peer-reviewed)abstract
- Treatment of autoimmune and inflammatory diseases typically involves immune suppression. In an opposite strategy, we show that administration of the highly inflammatory erythrocyte-specific antibody Ter119 into mice remodels the monocyte cellular landscape, leading to resolution of inflammatory disease. Ter119 with intact Fc function was unexpectedly therapeutic in the K/BxN serum transfer model of arthritis. Similarly, it rapidly reversed clinical disease progression in collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis and completely corrected CAIA-induced increase in monocyte Fcγ receptor II/III expression. Ter119 dose-dependently induced plasma chemokines CCL2, CCL5, CXCL9, CXCL10, and CCL11 with corresponding alterations in monocyte percentages in the blood and liver within 24 hours. Ter119 attenuated chemokine production from the synovial fluid and prevented the accumulation of inflammatory cells and complement components in the synovium. Ter119 could also accelerate the resolution of hypothermia and pulmonary edema in an acute lung injury model. We conclude that this inflammatory anti-erythrocyte antibody simultaneously triggers a highly efficient anti-inflammatory effect with broad therapeutic potential.
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| 3. |
- Kjeldsen-Kragh, Jens, et al.
(author)
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Towards a prophylactic treatment of HPA-related foetal and neonatal alloimmune thrombocytopenia.
- 2012
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In: Current Opinion in Hematology. - 1531-7048. ; 19:6, s. 469-474
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Journal article (peer-reviewed)abstract
- PURPOSE OF REVIEW: The purpose of the review is to show the similarities between haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) and to describe the background and challenges related to the current endeavours of developing a prophylaxis against FNAIT. The rationale for this prophylaxis is similar to the prophylaxis which has been used with great success for the last 40 years against RhD-associated HDFN. The idea is to prevent human platelet antigen (HPA)-1a-associated FNAIT by administering anti-HPA-1a immunoglobulin G (IgG) to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. RECENT FINDINGS: Results from a Norwegian screening and intervention study on FNAIT have indicated that about 75% of women with antibodies against HPA-1a are immunized in relation to delivery. This observation leads to the possibility of preventing HPA-1a-associated FNAIT in the same way as today's prevention of HDFN. Results from a proof-of-concept study in a murine FNAIT model have shown that the production of alloantibodies against platelets can be suppressed by administrating antiplatelet antibodies after the antigenic challenge. Even more interesting, the prophylactic antiplatelet antibodies could also significantly reduce the clinical consequences of FNAIT in this FNAIT model. SUMMARY: These novel observations have paved the way for clinical studies. Production and testing of anti-HPA-1a IgG for clinical use will be carried out by a European Union-funded consortium. If the results from the clinical trial are favourable, there is a chance that a medicinal product for the prevention of FNAIT will be available within this decade.
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| 4. |
- Li, June, et al.
(author)
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Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression
- 2023
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In: Research. - 2096-5168. ; 6
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Journal article (peer-reviewed)abstract
- Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell-Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.
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| 5. |
- Zdravic, Darko, et al.
(author)
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Fetal and neonatal alloimmune thrombocytopenia.
- 2016
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In: Seminars in Fetal & Neonatal Medicine. - : Elsevier BV. - 1878-0946 .- 1744-165X. ; 21:1, s. 19-27
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Research review (peer-reviewed)abstract
- Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an alloimmune disorder resulting from platelet opsonization by maternal antibodies that destroy fetal platelets. The major risk of FNAIT is severe bleeding, particularly intracranial hemorrhage. Miscarriage has also been reported but the incidence requires further study. Analogous to adult autoimmune thrombocytopenia (ITP), the major target antigen in FNAIT is the platelet membrane glycoprotein (GP)IIbIIIa. FNAIT caused by antibodies against platelet GPIbα or other antigens has also been reported, but the reported incidence of the anti-GPIbα-mediated FNAIT is far lower than in ITP. To date, the maternal immune response to fetal platelet antigens is still not well understood and it is unclear why bleeding is more severe in FNAIT than in ITP. In this review, we introduce the pathogenesis of FNAIT, particularly those new discoveries from animal models, and discuss possible improvements for the diagnosis, therapy, and prevention of this devastating disease.
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