When Will Fondaparinux Induce Thrombocytopenia?
Bioconjug Chem
; 33(8): 1574-1583, 2022 08 17.
Article
in English
| MEDLINE | ID: covidwho-1977960
ABSTRACT
The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4Fondaparinux concentration ratio.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Thrombocytopenia
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Bioconjug Chem
Journal subject:
Biochemistry
Year:
2022
Document Type:
Article
Affiliation country:
Acs.bioconjchem.2c00316
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