Glanzmann thrombasthenia
anti-αIIbβ3 isoantibodies
coagulation
complement activation
platelet transfusion
procoagulant platelet
Journal
Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
received:
24
05
2023
revised:
13
09
2023
accepted:
11
10
2023
medline:
25
1
2024
pubmed:
25
1
2024
entrez:
25
1
2024
Statut:
epublish
Résumé
Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet α In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties. Twelve patients with GT were evaluated for anti-α Only 2 samples were able to severely block integrin function. We observed that these 2 sera caused a reduction in platelet size similar to that observed when platelets become procoagulant. Mixing healthy donor platelets with patients' sera or purified IgGs led to microvesiculation, phosphatidylserine exposure, and induction of calcium influx. This was associated with an increase in procoagulant platelets. Pore formation and calcium entry were associated with complement activation, leading to the constitution of a membrane attack complex (MAC) with enhanced complement protein C5b-9 formation. This process was inhibited by the complement 5 inhibitor eculizumab and reduced by polyvalent human immunoglobulins. Our data suggest that complement activation induced by rare blocking anti-α
Sections du résumé
Background
UNASSIGNED
Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet α
Objectives
UNASSIGNED
In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties.
Methods
UNASSIGNED
Twelve patients with GT were evaluated for anti-α
Results
UNASSIGNED
Only 2 samples were able to severely block integrin function. We observed that these 2 sera caused a reduction in platelet size similar to that observed when platelets become procoagulant. Mixing healthy donor platelets with patients' sera or purified IgGs led to microvesiculation, phosphatidylserine exposure, and induction of calcium influx. This was associated with an increase in procoagulant platelets. Pore formation and calcium entry were associated with complement activation, leading to the constitution of a membrane attack complex (MAC) with enhanced complement protein C5b-9 formation. This process was inhibited by the complement 5 inhibitor eculizumab and reduced by polyvalent human immunoglobulins.
Conclusion
UNASSIGNED
Our data suggest that complement activation induced by rare blocking anti-α
Identifiants
pubmed: 38268518
doi: 10.1016/j.rpth.2023.102253
pii: S2475-0379(23)05678-9
pmc: PMC10805943
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102253Informations de copyright
© 2023 The Authors.