COVID-19 patients exhibit reduced procoagulant platelet responses.
COVID-19
infections
mitochondria
platelet activation
thrombosis
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
26
06
2020
revised:
27
08
2020
accepted:
08
09
2020
pubmed:
19
9
2020
medline:
29
12
2020
entrez:
18
9
2020
Statut:
ppublish
Résumé
Emerging evidence implicates dysfunctional platelet responses in thrombotic complications in COVID-19 patients. Platelets are important players in inflammation-induced thrombosis. In particular, procoagulant platelets support thrombin generation and mediate thromboinflammation. To examine if procoagulant platelet formation is altered in COVID-19 patients and if procoagulant platelets contribute to pulmonary thrombosis. Healthy donors and COVID-19 patients were recruited from the University of Utah Hospital System. Platelets were isolated and procoagulant platelet formation measured by annexin V binding as well as mitochondrial function were examined. We utilized mice lacking the ability to form procoagulant platelets (CypD We observed that platelets isolated from COVID-19 patients had a reduced ability to become procoagulant compared to those from matched healthy donors, as evidenced by reduced mitochondrial depolarization and phosphatidylserine exposure following dual stimulation with thrombin and convulxin. To understand what impact reduced procoagulant platelet responses might have in vivo, we subjected mice with a platelet-specific deletion of cyclophilin D, which are deficient in procoagulant platelet formation, to a model of pulmonary microvascular thrombosis. Mice with platelets lacking cyclophilin D died significantly faster from pulmonary microvascular thrombosis compared to littermate wild-type controls. These results suggest dysregulated procoagulant platelet responses may contribute to thrombotic complications during SARS-CoV-2 infection.
Sections du résumé
BACKGROUND
Emerging evidence implicates dysfunctional platelet responses in thrombotic complications in COVID-19 patients. Platelets are important players in inflammation-induced thrombosis. In particular, procoagulant platelets support thrombin generation and mediate thromboinflammation.
OBJECTIVES
To examine if procoagulant platelet formation is altered in COVID-19 patients and if procoagulant platelets contribute to pulmonary thrombosis.
PATIENTS/METHODS
Healthy donors and COVID-19 patients were recruited from the University of Utah Hospital System. Platelets were isolated and procoagulant platelet formation measured by annexin V binding as well as mitochondrial function were examined. We utilized mice lacking the ability to form procoagulant platelets (CypD
RESULTS AND CONCLUSIONS
We observed that platelets isolated from COVID-19 patients had a reduced ability to become procoagulant compared to those from matched healthy donors, as evidenced by reduced mitochondrial depolarization and phosphatidylserine exposure following dual stimulation with thrombin and convulxin. To understand what impact reduced procoagulant platelet responses might have in vivo, we subjected mice with a platelet-specific deletion of cyclophilin D, which are deficient in procoagulant platelet formation, to a model of pulmonary microvascular thrombosis. Mice with platelets lacking cyclophilin D died significantly faster from pulmonary microvascular thrombosis compared to littermate wild-type controls. These results suggest dysregulated procoagulant platelet responses may contribute to thrombotic complications during SARS-CoV-2 infection.
Identifiants
pubmed: 32945081
doi: 10.1111/jth.15107
pmc: PMC7646270
mid: NIHMS1639711
pii: S1538-7836(22)03752-7
doi:
Substances chimiques
Peptidyl-Prolyl Isomerase F
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3067-3073Subventions
Organisme : NHLBI NIH HHS
ID : K99 HL135265
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL153953
Pays : United States
Organisme : Fonds voor Wetenschappelijk Onderzoek Vlaanderen
ID : 12U7818N
Pays : International
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL142804
Pays : United States
Organisme : NIA NIH HHS
ID : R01AG048022
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142804
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL135265
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL135265
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG059877
Pays : United States
Organisme : NIA NIH HHS
ID : R56AG059877
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130541
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG059892
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG048022
Pays : United States
Organisme : CSRD VA
ID : I01 CX001696
Pays : United States
Organisme : NIA NIH HHS
ID : K01AG059892
Pays : United States
Informations de copyright
© 2020 International Society on Thrombosis and Haemostasis.
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