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10.1182/bloodadvances.2021005210

http://scihub22266oqcxt.onion/10.1182/bloodadvances.2021005210
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34753174!8580563!34753174
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suck abstract from ncbi


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pmid34753174      Blood+Adv 2022 ; 6 (1): 248-258
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  • Upregulation of cAMP prevents antibody-mediated thrombus formation in COVID-19 #MMPMID34753174
  • Zlamal J; Althaus K; Jaffal H; Haberle H; Pelzl L; Singh A; Witzemann A; Weich K; Bitzer M; Malek N; Gopel S; Bosmuller H; Gawaz M; Mirakaj V; Rosenberger P; Bakchoul T
  • Blood Adv 2022[Jan]; 6 (1): 248-258 PMID34753174show ga
  • Thromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. The exact mechanisms of COVID-19-associated hypercoagulopathy, however, remain elusive. Recently, we observed that platelets (PLTs) from patients with severe COVID-19 infection express high levels of procoagulant markers, which were found to be associated with increased risk for thrombosis. In the current study, we investigated the time course as well as the mechanisms leading to procoagulant PLTs in COVID-19. Our study demonstrates the presence of PLT-reactive IgG antibodies that induce marked changes in PLTs in terms of increased inner-mitochondrial transmembrane potential (Deltapsi) depolarization, phosphatidylserine (PS) externalization, and P-selectin expression. The IgG-induced procoagulant PLTs and increased thrombus formation were mediated by ligation of PLT Fc-gamma RIIA (FcgammaRIIA). In addition, contents of calcium and cyclic-adenosine-monophosphate (cAMP) in PLTs were identified to play a central role in antibody-induced procoagulant PLT formation. Most importantly, antibody-induced procoagulant events, as well as increased thrombus formation in severe COVID-19, were inhibited by Iloprost, a clinically approved therapeutic agent that increases the intracellular cAMP levels in PLTs. Our data indicate that upregulation of cAMP could be a potential therapeutic target to prevent antibody-mediated coagulopathy in COVID-19 disease.
  • |*COVID-19[MESH]
  • |*Thrombosis/etiology[MESH]
  • |Calcium[MESH]
  • |Humans[MESH]
  • |SARS-CoV-2[MESH]


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