Antibody-induced procoagulant platelets in severe COVID-19 infection
| العنوان: | Antibody-induced procoagulant platelets in severe COVID-19 infection |
|---|---|
| المؤلفون: | Irene Marini, Helene Häberle, Harald Schulze, Karina Althaus, Jan Zlamal, Anurag K. Singh, Stefanie Hammer, Dominik Rath, Michael Bitzer, Peter Rosenberger, Lisann Pelzl, Bernard Nieswandt, Hans Bösmüller, Nisar P. Malek, Martin Mehrländer, Tamam Bakchoul, Meinrad Gawaz |
| المصدر: | Blood |
| بيانات النشر: | American Society of Hematology, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Blood Platelets, Male, 0301 basic medicine, medicine.medical_specialty, Immunology, Apoptosis, Phosphatidylserines, 030204 cardiovascular system & hematology, Biochemistry, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Platelet, Receptor, Blood Coagulation, Aged, Membrane Potential, Mitochondrial, Calcium metabolism, SARS-CoV-2, business.industry, COVID-19, Regular Article, Thrombosis, Depolarization, Cell Biology, Hematology, Phosphatidylserine, Middle Aged, Platelets and Thrombopoiesis, medicine.disease, Pathophysiology, 030104 developmental biology, Endocrinology, chemistry, Immunoglobulin G, Calcium, Female, business |
| الوصف: | The pathophysiology of COVID-19 associated thrombosis seems to be multifactorial. We hypothesized that COVID-19 is accompanied by procoagulant platelets and platelet apoptosis with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization by flow cytometry. Platelets from intensive care unit (ICU) COVID-19 patients (n=21) showed higher ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization, compared to healthy controls (n=18) and COVID-19 non-ICU patients (n=4). Moreover significant higher cytosolic Ca2+ concentration and PS was observed compared to septic ICU control group (ICU control). In ICU control group (n=5; ICU non-COVID-19) cytosolic Ca2+ concentration and PS externalization was comparable to healthy control, with an increase in ΔΨm depolarization. Sera from ICU COVID-19 patients induced significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization) compared to healthy volunteer and septic ICU control. Interestingly, immunoglobulin G (IgG) fractions from COVID-19 patients induced an Fc gamma receptor IIA dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization). Enhanced PS externalization in platelets from ICU COVID-19 patients was associated with increased sequential organ failure assessment (SOFA) score (r=0.5635) and D-Dimer (r=0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared to those without. The strong correlations between procoagulant platelet and apoptosis markers and increased D-Dimer levels as well as the incidence of thrombosis may indicate that antibody-mediated platelet apoptosis potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc31a0519e0cfed412628b29f1901d85 https://doi.org/10.1182/blood.2020008762 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fc31a0519e0cfed412628b29f1901d85 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
|---|