Interference of Monoclonal Gammopathy with Fibrinogen Assay Producing Spurious Dysfibrinogenemia

Martini, Francesca; Cecconi, Nadia; Paolicchi, Aldo; Galimberti, Sara; Cervetti, Giulia; Buda, Gabriele; Petrini, Mario

doi:10.1055/s-0039-1683969

Cited by 6 publications

(7 citation statements)

References 7 publications

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“…These genes were found to be highly enriched in complement and coagulation cascades, platelet activation, and cytokine-cytokine receptor interaction ( Figure 7D). For instance, FGA/FGB/FGG genes encoding fibrinogen (Martini et al, 2019;Vilar et al, 2020) were hypermethylated and upregulated in IvC but were hypomethylated and downregulated in TvI (Figure 8A). Slc12a1, the key gene that mediates the electroneutral movement of Na(+) and K(+) across cell membranes (Schiessl et al, 2013;Xue et al, 2014;Hao et al, 2018;Kawaguchi et al, 2018), was hypomethylated and downregulated in IvC but hypermethylated and upregulated in TvI (Figure 8B).…”

Section: Conjoint Analyses Of M6a Modification and Gene Regulationmentioning

confidence: 99%

Integrated Analysis of m6A Methylome in Cisplatin-Induced Acute Kidney Injury and Berberine Alleviation in Mouse

Shen

Wang²,

Shao

et al. 2020

Front. Genet.

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BackgroundN6-methyladenosine (m6A) is the most abundant modification known in mRNAs. It participates in a variety of physiological and pathological processes, such as metabolism, inflammation, and apoptosis.AimsTo explore the mechanism of m6A in cisplatin-induced acute kidney injury (AKI) and berberine alleviation in mouse.MethodsThis study investigated the N6-methyladenosine (m6A) methylome of kidneys from three mouse groups: C57 mice (controls), those with CI-AKI (injury group, IG), and those pretreated with berberine (treatment group, TG). Methylated RNA Immunoprecipitation Next Generation Sequencing (MeRIP-seq) and RNA-seq were performed to identify the differences between the injury group and the control group (IvC) and between the treatment group and the injury group (TvI). Western blotting was performed to identify the protein levels of candidate genes.ResultsIn IvC, differentially methylated genes (DMGs) were enriched in metabolic processes and cell death. In TvI, DMGs were enriched in tissue development. Several genes involved in important pathways related to CI-AKI showed opposite methylation and expression trends in the IvC and TvI comparisons.Conclusionm6A plays an important role in cisplatin induced AKI and berberine may alleviate this process.

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Section: Conjoint Analyses Of M6a Modification and Gene Regulationmentioning

confidence: 99%

Integrated Analysis of m6A Methylome in Cisplatin-Induced Acute Kidney Injury and Berberine Alleviation in Mouse

Shen

Wang²,

Shao

et al. 2020

Front. Genet.

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“…Current literature lacks of data about a possible direct pathogenetic role of paraproteins in venous thrombosis [16]. In some case reports, the monoclonal light chain is identified as an interfering factor in functional assays and coagulation tests causing dysfibrinogenemia [17]. In our case, a lot of contributory factors are involved in the development of the prothrombotic state, such as obesity, very high levels of free light chains and hypoalbuminemia.…”

Section: Discussionmentioning

confidence: 69%

A multidisciplinary case report of multiple myeloma with renal and cardiac involvement: a look beyond amyloidosis

et al. 2022

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Background Multiple myeloma (MM) is a malignant neoplasm associated with kidney involvement in nearly half of the patients. Cast nephropathy, monoclonal immunoglobulin deposition disease (MIDD), and light chain (AL) amyloidosis are the most common monoclonal immunoglobulin-mediated causes of renal injury. Cardiac involvement is also present in MM, characterized by restrictive cardiomyopathy generated by light chain deposit or amyloid. Thromboembolic complications such as deep vein thrombosis or pulmonary embolism are also described. Case presentation We present an unusual multidisciplinary case of a woman with a newly diagnosed MM associated with severe proteinuria and high natriuretic peptide. A renal and fat pad biopsy with Congo red staining were performed but amyloid deposition was not discovered. While immunofluorescence on fresh frozen unfixed tissue was not contributory, the immunofluorescence on fixed tissue and electron microscopy revealed the correct diagnosis. During subsequent investigations, two intracardiac right-sided masses and massive pulmonary embolism were also detected. Conclusions This case highlights that multiple organ involvement in patients with MM may result from a combination of paraprotein-dependent and -independent factors. Moreover, renal diseases induced by monoclonal gammopathies are a group of complex and heterogeneous disorders. Their subtle presentation and their potential multiorgan involvement require the expertise of a multidisciplinary team able to provide the most appropriate diagnostic and therapeutic assessment.

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“…Paraproteinemia may impair fibrin formation by either antigen-antibody interactions, nonspecific interactions or increasing plasma viscosity. 88 ELISA and Western blotting experiments are needed to confirm an antibody-antigen interaction of paraprotein with FBG. 89 It is generally accepted that increased FBG levels are an independent risk factor for cardiovascular disease, 90 even though a clear genetic link between FBG level and thrombotic risk has not been found yet.…”

Section: Clinical Utility Of Testsmentioning

confidence: 99%

“…Finally, FBG assessment is useful for investigation and monitoring of miscellaneous causes of acquired hypofibrinogenaemia and dysfibrinogenaemia such as plasma exchange using albumin as a replacement fluid, medications that may impair hepatic synthesis (e.g., L‐asparaginase, tigecycline, valproic acid, thrombolytic drugs), snake envenomation 86,87 and multiple myeloma. Paraproteinemia may impair fibrin formation by either antigen–antibody interactions, nonspecific interactions or increasing plasma viscosity 88 . ELISA and Western blotting experiments are needed to confirm an antibody–antigen interaction of paraprotein with FBG 89 …”

Section: Clinical Utility Of Testsmentioning

confidence: 99%

International council for standardisation in haematology recommendations on fibrinogen assays, thrombin clotting time and related tests in the investigation of bleeding disorders

Mackie,

Casini,

Pieters

et al. 2023

Int J Lab Hematology

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This guidance was prepared on behalf of the International Council for Standardisation in Haematology (ICSH) by an international working group of clinicians and scientists. The document focuses on tests and assays used for the assessment of fibrinogen function, particularly in the scenario of bleeding disorders. Thrombin clotting time (TT) is used as a screening test in some laboratories and also has some utility when direct anticoagulants are in use. The Clauss fibrinogen assay remains the method of choice for the assessment of fibrinogen function, but there are some situations where the results may be misleading. Prothrombin time derived fibrinogen assays are frequently used, but should be interpreted with caution; the results are not interchangeable between different methods and fibrinogen can be overestimated in certain clinical scenarios. Viscoelastic point of care methods may be helpful in emergency situations, while Reptilase time (and similar tests) are useful combined with TT in distinguishing heparin contamination of samples (i.e., if an incorrect blood draw is suspected) and the presence of direct thrombin inhibitors. Fibrinogen antigen assays should be used in the investigation of functional fibrinogen abnormalities; fibrinogen antigen and genetic testing are recommended in the confirmation of congenital fibrinogen disorders. The following recommendations for fibrinogen function assessment are based on published literature and expert opinion and should supplement local regulations and standards.

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Interference of Monoclonal Gammopathy with Fibrinogen Assay Producing Spurious Dysfibrinogenemia

Cited by 6 publications

References 7 publications

Integrated Analysis of m6A Methylome in Cisplatin-Induced Acute Kidney Injury and Berberine Alleviation in Mouse

Integrated Analysis of m6A Methylome in Cisplatin-Induced Acute Kidney Injury and Berberine Alleviation in Mouse

A multidisciplinary case report of multiple myeloma with renal and cardiac involvement: a look beyond amyloidosis

International council for standardisation in haematology recommendations on fibrinogen assays, thrombin clotting time and related tests in the investigation of bleeding disorders

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