Acquired Dysfibrinogenemia Secondary to Multiple Myeloma

Kotlín, Roman; Sobotková, Alžběta; Riedel, Tomáš; Salaj, Peter; Suttnar, Jiřı́; Reicheltová, Zuzana; Májek, Pavel; Khaznadar, Tarek; Dyr, Jan E.

doi:10.1159/000160182

Cited by 32 publications

(10 citation statements)

References 56 publications

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“…Kotlín et al described a case of myeloma paraprotein immunoglobulin G interfering with fibrin polymerization: enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments confirmed the antibody–antigen interaction of paraprotein with Fg. 10 The normalization of coagulation assays occurred after melphalan–prednisone treatment as in our patient after dexamethasone treatment. In our patient we could exclude an antibody–antigen interaction because a single light chain is involved.…”

Section: Discussionsupporting

confidence: 65%

Interference of Monoclonal Gammopathy with Fibrinogen Assay Producing Spurious Dysfibrinogenemia

Martini

Cecconi

Paolicchi

et al. 2019

TH Open

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Abnormal coagulation properties indicative of a dysfibrinogenemia were found in the plasma of an asymptomatic 65-year-old male. An immunoglobulin k light chain was found to interfere with Fg functional assay and coagulation tests (activated partial thromboplastin time, prothrombin time, and thrombin time). Steroid therapy reduced the inhibitory effect (after dexamethasone treatment coagulation test and functional Fg value normalized). Spurious dysfibrinogenemia associated with light chain monoclonal gammopathy of undetermined significance was diagnosed.

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Section: Discussionsupporting

confidence: 65%

Interference of Monoclonal Gammopathy with Fibrinogen Assay Producing Spurious Dysfibrinogenemia

Martini

Cecconi

Paolicchi

et al. 2019

TH Open

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“… 26 BβH67 interacts with γD297, and BβH67L (fibrinogen Sumperk) resulted in hypofibrinogenemia associated with bleeding, delayed polymerization, and abnormal clot properties. 61 Residue γE323 interacts with Bβ58, which is abnormal in fibrinogen Christchurch V (BβK58 > frameshift41aa-stop) resulting in a truncated β chain, 62 but in this case, the clinical phenotype is likely the result of the truncated protein.…”

Section: Discussionmentioning

confidence: 98%

Fibrin protofibril packing and clot stability are enhanced by extended knob-hole interactions and catch-slip bonds

et al. 2022

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Fibrin polymerisation involves thrombin-mediated exposure of knobs on one monomer that bind to holes available on another, leading to the formation of fibers. In silico evidence has suggested that the classical A:a knob-hole interaction is enhanced by surrounding residues not directly involved in the binding pocket of hole 'a', via non-covalent interactions with knob 'A'. We assessed the importance of extended knob-hole interactions by performing biochemical, biophysical and in silico modelling studies on recombinant human fibrinogen variants with mutations at residues responsible for the extended interactions. Three single fibrinogen variants, γD297N, γE323Q and γK356Q and a triple variant, γDEK (γD297N/γE323Q/γK356Q) were produced in a CHO cell expression system. Longitudinal protofibril growth probed by atomic force microscopy was disrupted for γD297N and enhanced for γK356Q mutation. Initial polymerisation rates were reduced for all variants in turbidimetric studies. Laser scanning confocal microscopy showed that γDEK and γE323Q produced denser clots, whereas γD297N and γK356Q were similar to WT. Scanning electron microscopy and light scattering studies showed that fiber thickness and protofibril packing of the fibers were reduced for all variants. Clot viscoelastic analysis showed that only γDEK was more readily deformable. In silico modelling suggested that most variants displayed only slip-bond dissociation kinetics compared to biphasic catch-slip kinetics characteristics of WT. These data provide new evidence for the role of extended interactions in supporting the classical knob-hole bonds involving catch-slip behaviour, in fibrin formation, clot structure, and clot mechanics.

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“…20 Indeed, purified polyclonal and monoclonal myeloma IgG up to the concentration of 15 mg/mL have been associated with the formation of thin fibrin fibers with almost negligible susceptibility to plasmin-mediated fibrinolysis, suggesting that such clot structure may contribute to high thrombotic risk in patients with multiple myeloma. 21 In 2008, Kotlín et al 22 described a multiple myeloma patient who developed acquired dysfibrinogenemia related to high paraprotein IgGκ concentrations (86 g/L). Interestingly, in this case report, thrombin activation reflected by the kinetics of fibrinopeptide release and formation of fibrin monomers were normal, while fibrin did not polymerize.…”

Section: Fibrin Clot Properties In Specific Diseasesmentioning

confidence: 99%

Fibrin Clot Properties in Cancer: Impact on Cancer-Associated Thrombosis

Ząbczyk

Undas

2023

Semin Thromb Hemost

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Cancer is associated with a high risk of venous thromboembolism (VTE) and its recurrence. There is evidence that the prothrombotic fibrin clot phenotype, involving the formation of denser and stiffer clots relatively resistant to lysis, occurs in cancer patients, which is in part related to enhanced inflammation, oxidative stress, and coagulation activation, along with the release of neutrophil extracellular traps, indicating that fibrin-related mechanisms might contribute to cancer-associated thrombosis (CAT). Multiple myeloma and its therapy have been most widely explored in terms of altered fibrin characteristics, but prothrombotic fibrin clot features have also been reported in patients with active solid cancer, including lung cancer and gastrointestinal cancer. Patient-related factors such as advanced age, smoking, and comorbidities might also affect fibrin clot characteristics and the risk of CAT. Prothrombotic fibrin clot features have been shown to predict the detection of cancer in patients following VTE during follow-up. Cancer-specific therapies and anticoagulation can favorably modify the phenotype of a fibrin clot, which may alter the course of CAT. It is unclear whether the fibrin clot phenotype might help identify patients with CAT who are more likely to experience recurrent events. This narrative review summarizes the current knowledge on the role of fibrin clot structure and function in cancer patients in the context of CAT.

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Acquired Dysfibrinogenemia Secondary to Multiple Myeloma

Cited by 32 publications

References 56 publications

Interference of Monoclonal Gammopathy with Fibrinogen Assay Producing Spurious Dysfibrinogenemia

Interference of Monoclonal Gammopathy with Fibrinogen Assay Producing Spurious Dysfibrinogenemia

Fibrin protofibril packing and clot stability are enhanced by extended knob-hole interactions and catch-slip bonds

Fibrin Clot Properties in Cancer: Impact on Cancer-Associated Thrombosis

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