Monoclonal whole IgG impairs both fibrin and thrombin formation: hemostasis and surface plasmon resonance studies
Author:
Gonda Lénárd1, Torner Bernadett1, Ghansah Harriet1, Beke Debreceni Ildikó1, Váróczy László1, Pénzes-Daku Krisztina1, Kappelmayer János1
Affiliation:
1. Department of Laboratory Medicine, Department of Hematology, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
Abstract
Abstract
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.
Publisher
Walter de Gruyter GmbH
Reference25 articles.
1. Ghansah, H, Debreceni, IB, Váróczy, L, Rejtő, L, Lóczi, L, Bagoly, Z, et al.. Patients with multiple myeloma and monoclonal gammopathy of undetermined significance have variably increased thrombin generation and different sensitivity to the anticoagulant effect of activated protein C. Thromb Res 2023;223:44–52. https://doi.org/10.1016/j.thromres.2023.01.010. 2. Ghansah, H, Orbán-Kálmándi, R, Debreceni, IB, Katona, É, Rejtő, L, Váróczy, L, et al.. Low factor XIII levels and altered fibrinolysis in patients with multiple myeloma. Thromb Res 2023;234:12–20. https://doi.org/10.1016/j.thromres.2023.12.004. 3. Li, P, Xu, B, Xu, J, Xu, Y, Wang, Y, Chen, C, et al.. Lenalidomide promotes thrombosis formation, but does not affect platelet activation in multiple myeloma. Int J Mol Sci 2023;24:14097. https://doi.org/10.3390/ijms241814097. 4. Nielsen, T, Kristensen, SR, Gregersen, H, Teodorescu, EM, Pedersen, S. Prothrombotic abnormalities in patients with multiple myeloma and monoclonal gammopathy of undetermined significance. Thromb Res 2021;202:108–18. https://doi.org/10.1016/j.thromres.2021.03.015. 5. Yokoyama, K. Thrombosis in lymphoma patients and in myeloma patients. Keio J Med 2015;64:37–43. https://doi.org/10.2302/kjm.2014-0017-re.
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