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001-es BibID:BIBFORM125745
035-os BibID:(scopus)85197919739 (wos)001252813300001
Első szerző:Gonda Lénárd (Általános orvos)
Cím:Monoclonal whole IgG impairs both fibrin and thrombin formation : hemostasis and surface plasmon resonance studies / Gonda Lénárd, Torner Bernadett, Ghansah Harriet, Beke Debreceni Ildikó, Váróczy László, Pénzes-Daku Krisztina, Kappelmayer János
Dátum:2024
ISSN:1434-6621
Megjegyzések:Objectives: Monoclonal gammopathies frequently associate with hemostatic alterations. Thrombotic events occur with high incidence particularly upon treatment, while in rarer cases hemorrhagic diathesis can be observed. The pathology of these tendencies could be caused by thrombocytopenia or hyperviscosity burden of circulating monoclonal antibodies. Studies also suggest interference of monoclonal antibodies with primary hemostasis. We isolated monoclonal whole IgG paraproteins from two myeloma patients to observe their effect on thrombin formation and fibrin polymerization. Methods: Monoclonal whole IgG was prepared from sera of two newly diagnosed untreated multiple myeloma patients and control normal plasma samples. Fibrin formation was measured using thrombin time and dilute prothrombin time tests and thrombin formation was detected with a fluorimetric thrombin generation assay. In addition, molecular interactions were investigated by surface plasmon resonance (SPR). Results: Thrombin time was prolonged upon addition of monoclonal IgG even at 30 g/L by 12 %, increasing up to 36 % at 60 g/L concentration. Dilute prothrombin time was prolonged by 20 % even at 30 g/L. Thrombin generation assay indicated an impairment in thrombin formation at the presence of monoclonal IgG compared to polyclonal at equivalent concentration. By an SPR assay we determined that both clonality IgG preparations interacted with fibrinogen, however interaction with human thrombin was only detected with monoclonal immunoglobulins (KD=1.03 ? 10-7 M). Conclusions: Here we provide evidence that isolated monoclonal whole IgG from myeloma patients can impair both fibrin and thrombin formation and we demonstrate by SPR assay that it interacts with components of the final phase of the coagulation system.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
fibrinogen
monoclonal IgG
Myelóma multiplex
trombin
Megjelenés:Clinical Chemistry And Laboratory Medicine. - 62 : 9 (2024), p. 1863-1869. -
További szerzők:Torner Bernadett (1997-) (molekuláris biológus) Ghansah, Harriet (1987-) (PhD) Bekéné Debreceni Ildikó (1970-) (biológus) Váróczy László (1974-) (belgyógyász, haematológus) Pénzes-Daku Krisztina (1978-) (biológus) Kappelmayer János (1960-) (absztraktok)
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