| 1. |
- Chao, Yashuan, et al.
(författare)
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Distinct phenotypes of platelet, monocyte, and neutrophil activation occur during the acute and convalescent phase of COVID-19
- 2021
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635.
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 has spread rapidly worldwide, causing the COVID-19 pandemic. Platelet activation and platelet-leukocyte complex formation are proposed to contribute to disease progression. Here, we report platelet and leukocyte activation during acute and convalescent COVID-19 in patients recruited between May-July 2020. Blood samples were analyzed by flow cytometry and ELISA using paired comparison between inclusion (day 0) and 28 days later. The majority of patients were mildly or moderately ill with significantly higher cytokine levels (IL-6 and IL-10) on day 0 as compared with day 28. Platelet activation and granule release were significantly higher on day 0 compared with day 28, as determined by ADP- or thrombin-induced surface CD62P expression, baseline released CD62P, and thrombin-induced platelet-monocyte complex formation. Monocyte activation and procoagulant status at baseline and post activation were heterogeneous but generally lower on day 0 compared with day 28. Baseline and thrombin- or fMLF-induced neutrophil activation and procoagulant status were significantly lower on day 0 compared with day 28. We demonstrate that during the acute phase of COVID-19 compared with the convalescent phase, platelets are more responsive while neutrophils are less responsive. COVID-19 is associated with thromboembolic events where platelet activation and interaction with leukocytes may play an important role.
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| 2. |
- McVey, Mark J, et al.
(författare)
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Transfusion-related Acute Lung Injury in the Perioperative Patient
- 2019
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Ingår i: Anesthesiology. - 1528-1175. ; 131:3, s. 693-715
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Forskningsöversikt (refereegranskat)abstract
- Transfusion-related acute lung injury is a leading cause of death associated with the use of blood products. Transfusion-related acute lung injury is a diagnosis of exclusion which can be difficult to identify during surgery amid the various physiologic and pathophysiologic changes associated with the perioperative period. As anesthesiologists supervise delivery of a large portion of inpatient prescribed blood products, and since the incidence of transfusion-related acute lung injury in the perioperative patient is higher than in nonsurgical patients, anesthesiologists need to consider transfusion-related acute lung injury in the perioperative setting, identify at-risk patients, recognize early signs of transfusion-related acute lung injury, and have established strategies for its prevention and treatment.
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| 3. |
- Semple, John W, et al.
(författare)
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Transfusion-associated circulatory overload and transfusion-related acute lung injury.
- 2019
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 133:17, s. 1840-1853
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Forskningsöversikt (refereegranskat)abstract
- Transfusion-associated circulatory overload (TACO) and Transfusion-related acute lung injury (TRALI) are syndromes of acute respiratory distress which occur within 6 hours of blood transfusion. TACO and TRALI are the leading causes of transfusion-related fatalities and specific therapies are unavailable. Diagnostically, it remains very challenging to distinguish TACO and TRALI from underlying causes of lung injury and/or fluid overload as well as from each other. TACO is characterized by pulmonary hydrostatic (cardiogenic) edema, while TRALI presents as pulmonary permeability edema (noncardiogenic). The pathophysiology of both syndromes is complex and incompletely understood. A 2-hit model is generally assumed to underlie TACO and TRALI disease pathology where the first hit represents the clinical condition of the patient and the second hit is conveyed by the transfusion product. In TACO, cardiac- or renal impairment and positive fluid balance appear first hits while suboptimal fluid management or other components in the transfused product may enable the second hit. Remarkably, other factors beyond volume play a role in TACO. In TRALI, the first hit can, for example, be represented by inflammation while the second hit is assumed to be caused by anti-leukocyte antibodies or biological response modifiers (e.g. lipids). In this review, we provide an up-to-date overview of TACO and TRALI regarding clinical definitions, diagnostic strategies, pathophysiological mechanisms and potential therapies. More research is required to better understand the TACO and TRALI pathophysiology and more biomarker studies are warranted. Collectively, this may result in improved diagnostics and development of therapeutic approaches for these life-threating transfusion reactions.
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| 4. |
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| 5. |
- Balduini, Carlo, et al.
(författare)
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The EHA research roadmap : Platelet disorders
- 2021
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Ingår i: HemaSphere. - 2572-9241. ; 5:7
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Forskningsöversikt (refereegranskat)abstract
- In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1 to 2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cellbased Immune Therapies; and Gene Therapy.
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| 6. |
- Bussel, James B., et al.
(författare)
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A review of romiplostim mechanism of action and clinical applicability
- 2021
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Ingår i: Drug Design, Development and Therapy. - 1177-8881. ; 15, s. 2243-2268
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Forskningsöversikt (refereegranskat)abstract
- Thrombocytopenia results from a variety of conditions, including radiation, chemotherapy, autoimmune disease, bone marrow disorders, pathologic conditions associated with surgical procedures, hematopoietic stem cell transplant (HSCT), and hematologic disorders associated with severe aplastic anemia. Immune thrombocytopenia (ITP) is caused by immune reactions that accelerate destruction and reduce production of platelets. Thrombopoietin (TPO) is a critical component of platelet production pathways, and TPO receptor agonists (TPO-RAs) are important for the management of ITP by increasing platelet production and reducing the need for other treatments. Romiplostim is a TPO-RA approved for use in patients with ITP in the United States, European Union, Australia, and several countries in Africa and Asia, as well as for use in patients with refractory aplastic anemia in Japan and Korea. Romiplostim binds to and activates the TPO receptor on megakaryocyte precursors, thus promoting cell proliferation and viability, resulting in increased platelet production. Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. In addition to its efficacy in ITP, studies have shown that romiplostim is effective in improving platelet counts in various settings, thereby highlighting the versatility of romiplostim. The efficacy of romiplostim in such disorders is currently under investigation. Here, we review the structure, mechanism, pharmacokinetics, and pharmacodynamics of romiplostim. We also summarize the clinical evidence supporting its use in ITP and other disorders that involve thrombocytopenia, including chemotherapy-induced thrombocytopenia, aplastic anemia, acute radiation syndrome, perisurgical thrombocytopenia, post-HSCT thrombocytopenia, and liver disease.
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| 7. |
- Bussel, James, et al.
(författare)
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Mechanisms and therapeutic prospects of thrombopoietin receptor agonists
- 2019
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Ingår i: Seminars in Hematology. - : Elsevier BV. - 0037-1963. ; 56:4, s. 262-278
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Forskningsöversikt (refereegranskat)abstract
- The second-generation thrombopoietin (TPO) receptor agonists eltrombopag and romiplostim are potent activators of megakaryopoiesis and represent a growing treatment option for patients with thrombocytopenic hematological disorders. Both TPO receptor agonists have been approved worldwide for the treatment of children and adults with chronic immune thrombocytopenia. In the EU and USA, eltrombopag is approved for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy and in the USA for the first-line treatment of severe aplastic anemia in combination with immunosuppressive therapy. Eltrombopag has also shown efficacy in several other disease settings, for example, chemotherapy-induced thrombocytopenia, selected inherited thrombocytopenias, and myelodysplastic syndromes. While both TPO receptor agonists stimulate TPO receptor signaling and enhance megakaryopoiesis, their vastly different biochemical structures bestow upon them markedly different molecular and functional properties. Here, we review and discuss results from preclinical and clinical studies on the functional and molecular mechanisms of action of this new class of drug.
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| 8. |
- Jongerius, Ilse, et al.
(författare)
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The Role of Complement in Transfusion-Related Acute Lung Injury
- 2019
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Ingår i: Transfusion Medicine Reviews. - : Elsevier BV. - 0887-7963. ; 33:4, s. 236-242
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Forskningsöversikt (refereegranskat)abstract
- Transfusion-related acute lung injury (TRALI) is a life-threatening complication of acute respiratory distress occurring within 6 hours of blood transfusion. TRALI is one of the leading causes of transfusion-related fatalities and specific therapies are unavailable. Neutrophils are recognized as the major pathogenic cells, whereas T regulatory cells and dendritic cells appear to be important for protection against TRALI. The pathogenesis, however, is complex and incompletely understood. It is frequently postulated that the complement system plays an important role in the TRALI pathogenesis. In this article, we assess the evidence regarding the involvement of complement in TRALI from both human and animal studies. We hypothesize about the potential connection between the complement system and neutrophils in TRALI. Additionally, we draw parallels between TRALI and other acute pulmonary disorders of acute lung injury and acute respiratory distress syndrome regarding the involvement of complement. We conclude that, even though a role for complement in the TRALI pathogenesis seems plausible, studies investigating the role of complement in TRALI are remarkably limited in number and also present conflicting findings. Different types of TRALI animal models, diverse experimental conditions, and the composition of the gastrointestinal microbiota may perhaps all be factors which contribute to these discrepancies. More systematic studies are warranted to shed light on the contribution of the complement cascade in TRALI. The underlying clinical condition of the patient, which influences the susceptibility to TRALI, as well as the transfusion factor (antibody-mediated vs non–antibody-mediated), will be important to take into consideration when researching the contribution of complement. This should significantly increase our understanding of the role of complement in TRALI and may potentially result in promising new treatment strategies.
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| 9. |
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| 10. |
- Kapur, Rick, et al.
(författare)
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Binge-reading on immune thrombocytopenia : Everything you ever wanted to know
- 2023
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 201:5, s. 811-812
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Tidskriftsartikel (refereegranskat)abstract
- Immune thrombocytopenia (ITP) is a complex clinical and pathophysiological autoimmune disorder and in the past decade, thousands of papers have been published on this topic. To shed light on the global scientific output, Ou et al. performed a comprehensive bibliometric analysis of the ITP literature to clarify the major hotspots and future research directions. Commentary on: Ou et al. A bibliometric analysis of primary immune thrombocytopenia from 2011 to 2021. Br J Haematol 2023 (Online ahead of print). doi: 10.1111/bjh.18692.
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