Monoclonal whole IgG impairs both fibrin and thrombin formation: hemostasis and surface plasmon resonance studies

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dc.contributor.advisorKappelmayer, János
dc.contributor.advisordeptÁltalános Orvostudományi Kar::Laboratóriumi Medicina Intézet
dc.contributor.authorGonda, Lénárd Zoltán
dc.contributor.departmentDE--Általános Orvostudományi Kar
dc.contributor.opponentdeptEgyetemen kívüli
dc.date.accessioned2025-05-14T08:06:42Z
dc.date.available2025-05-14T08:06:42Z
dc.date.created2024-06-25
dc.description.abstractAbstract 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.
dc.description.courseáltalános orvos
dc.description.courseactnappali
dc.description.courselangmagyar
dc.description.degreeegységes, osztatlan
dc.format.extent7
dc.identifier.urihttps://hdl.handle.net/2437/389888
dc.language.isoen
dc.rights.infoHozzáférhető a 2022 decemberi felsőoktatási törvénymódosítás értelmében.
dc.subjectfibrinogen; monoclonal IgG; multiple myeloma; thrombin
dc.subject.dspaceOrvostudomány::Belgyógyászat
dc.titleMonoclonal whole IgG impairs both fibrin and thrombin formation: hemostasis and surface plasmon resonance studies
dc.title.translatedMonoclonal whole IgG impairs both fibrin and thrombin formation: hemostasis and surface plasmon resonance studies
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