Prothrombotic abnormalities in patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Nielsen, Thøger; Kristensen, Søren Risom; Gregersen, Henrik; Teodorescu, Elena Manuela; Pedersen, Shona

doi:10.1016/j.thromres.2021.03.015

Cited by 18 publications

(20 citation statements)

References 41 publications

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“…In addition, tumor cells metastasize and invade tissues and organs, resulting in tissue damage and endothelial cell damage. After endothelial cell injury, a large number of tissue factors can be released to activate the body's coagulation system, which then leads to coagulation-fibrinolysis dysfunction in patients [ 9 , 10 ]. D-dimer (D-D), fibrinogen (FIB), prothrombin time (PT), etc.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Coagulation Abnormality in Patients with Multiple Myeloma and Its Clinical Significance

Pan

Liu

2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To analyze the abnormal changes of coagulation indexes in patients with multiple myeloma (MM) and their clinical significance on prognosis. Methods. Among 80 patients with MM, there were 24 patients of light chain type, 36 patients of IgG type, and 20 patients of IgA type. In the same period, 30 healthy people were in the control group. The laboratory indexes such as plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thromboplastin time (TT), D-dimer (D-D), and platelet (PLT) were detected and compared. The prognosis of MM patients was followed up, and the effects of various coagulation indexes on the prognosis of MM were analyzed by single-factor and multifactor analyses. Results. The PT and APTT of IgG and IgA groups were longer than those of the control group and the light chain group ( P < 0.05 ), but there was no significant difference between the IgG group and the IgA group, the control group, and the light chain group. There was no significant difference in FIB values among the four groups ( P > 0.05 ). The D-D content in the light chain group was higher than that in the control group, the IgG group, and the IgA group ( P < 0.05 ). During the follow-up period, of 80 MM patients, 61 patients survived and 19 patients died. Univariate analysis showed that APTT, PT, and D-D were the factors affecting the prognosis of MM patients, and the differences were statistically significant ( P < 0.05 ). Multivariate analysis showed that PT was an independent factor affecting the prognosis of MM patients ( P < 0.05 ). Discussion. Patients with MM have clotting abnormalities. Patients with IgA and IgG type MM have a longer clotting time than patients with other types of MM, and patients with light-chain type MM have higher D-D content and are more prone to thrombosis. PT is an independent factor affecting the prognosis of MM patients, and analysis of coagulation abnormalities is important for evaluating the prognosis of patients.

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Section: Introductionmentioning

confidence: 99%

Analysis of Coagulation Abnormality in Patients with Multiple Myeloma and Its Clinical Significance

Pan

Liu

2022

Evidence-Based Complementary and Alternative Medicine

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“…Two studies proposed that hypercoagulability in MM arises from thrombin generation due to clotting activation via TF and phospholipids activity [ 16 , 17 ]. Our result is in agreement with Auwerda et al, who detailed, that in a MM cohort under chemotherapy, elevated MV-TF activity in patients who developed VTE, in contrast to patients who do not develop VTE [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Incidence of Venous Thromboembolism in Multiple Myeloma Patients across Different Regimens: Role of Procoagulant Microparticles and Cytokine Release

Gidaro

Manetti

Delitala

et al. 2022

JCM

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Introduction: Multiple myeloma (MM) is characterized by a high prevalence of thrombotic complications. Microvesicles (MVs) are small membrane vesicles released from activated cells, and they may potentially contribute to thrombosis. Methods: We have evaluated the plasma levels of MVs and cytokines (IL-10, IL-17, and TGF-β in MM and Watch and Wait Smoldering MM (WWSMM) from patients and related them to thrombotic complications. The secondary aim was to assess the impact of ongoing therapy on MV and on cytokine levels. Result: 92 MM and 31 WWSMM were enrolled, and 14 (12%) experienced a thrombotic episode. Using univariate analysis, TGF-β and MV were significantly higher in patients with thrombotic events (p = 0.012; p = 0.008, respectively). Utilizing a Cox proportional hazard model, we confirmed this difference (TGF-β p = 0.003; Odds ratio 0.001, 95% CI 0–0.003 and MV p = 0.001; Odds ratio 0.003, 95% CI 0.001–0.005). Active treatment management displayed higher levels of MV (p < 0.001) and lower levels of glomerular filtration-rate (p < 0.001), IL-17 (p < 0.001) as compared to the WWSMM group. The TGF-β values of immunomodulatory derivatives patients were lower in the WWSMM (p < 0.001) and Dexamethasone/Bortezomib subgroup (p < 0.001). Conclusion: The increased levels of MVs in active regimens add insight into the mechanisms of hypercoagulation in MM. In addition, a role for cytokine-related thrombosis is also suggested.

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“…In general, patients suffering from plasma cell dyscrasias, especially multiple myeloma, are at increased risk of hypercoagulability and venous thromboembolism development [6][7][8][9][10][11]. As many as 10% of patients suffering from multiple myeloma are affected by venous thrombotic events (VTE), which are found to be associated with the risk of pre-term death [6].…”

Section: Hypercoagulability In Plasma Cell Dyscrasiasmentioning

confidence: 99%

“…Moreover, products of neoplastic plasma cells appear to have lupus anticoagulant-like activity, and autoantibodies decrease the level of antithrombin and proteins S and C, which are important natural anticoagulants [10,12]. Factors that are unrelated to the presence of monoclonal proteins are: increased concentration of inflammatory cytokines (interleukin 6 (IL-6); tumor necrosis factor-α (TNF-α); vascular endothelial growth factor (VEGF)), which in turn increases the production of procoagulant von Willebrand factor (vWF), fibrinogen, or tissue factor (TF) [11,12]. Finally, it has been reported that myeloma cells release specific microparticles that express tissue factor (TF) and promote hypercoagulability [7,10,11,14] (Figure 1).…”

Section: Hypercoagulability In Plasma Cell Dyscrasiasmentioning

confidence: 99%

“…Factors that are unrelated to the presence of monoclonal proteins are: increased concentration of inflammatory cytokines (interleukin 6 (IL-6); tumor necrosis factor-α (TNF-α); vascular endothelial growth factor (VEGF)), which in turn increases the production of procoagulant von Willebrand factor (vWF), fibrinogen, or tissue factor (TF) [11,12]. Finally, it has been reported that myeloma cells release specific microparticles that express tissue factor (TF) and promote hypercoagulability [7,10,11,14] (Figure 1). Detailed mechanisms of the procoagulant action of immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide remain unknown [8]; however, observational studies report that the use of these medications in mono-or multidrug-therapy may increase the risk of VTE by up to 30% [6].…”

Section: Hypercoagulability In Plasma Cell Dyscrasiasmentioning

confidence: 99%

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Neutrophil Extracellular Traps (NETs) and Hypercoagulability in Plasma Cell Dyscrasias—Is This Phenomenon Worthy of Exploration?

Ciepiela

Małecka‐Giełdowska

Czyżewska

2021

JCM

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Plasma cell dyscrasias (PCDs) are neoplastic diseases derived from plasma cells. Patients suffering from PCDs are at high risk of hypercoagulability and thrombosis. These conditions are associated with disease-related factors, patient-related factors, or the use of immunomodulatory drugs. As PCDs belong to neoplastic diseases, some other factors related to the cancer-associated hypercoagulability state in the course of PCDs are also considered. One of the weakest issues studied in PCDs is the procoagulant activity of neutrophil extracellular traps (NETs). NETs are web-like structures released from neutrophils in response to different stimuli. These structures are made of deoxyribonucleic acid (DNA) and bactericidal proteins, such as histones, myeloperoxidase, neutrophil elastase, and over 300 other proteins, which are primarily stored in neutrophil granules. NETs immobilize, inactivate the pathogens, and expose them to specialized cells of immune response. Despite their pivotal role in innate immunity, they contribute to the development and exacerbation of autoimmune diseases, trigger inflammatory response, or even facilitate the formation of cancer metastases. NETs were also found to induce activity of coagulation and are considered one of the most important factors inducing thrombosis. Here, we summarize how PCDs influence the release of NETs, and hypothesize whether NETs contribute to hypercoagulability in PCDs patients.

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Prothrombotic abnormalities in patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Cited by 18 publications

References 41 publications

Analysis of Coagulation Abnormality in Patients with Multiple Myeloma and Its Clinical Significance

Analysis of Coagulation Abnormality in Patients with Multiple Myeloma and Its Clinical Significance

Incidence of Venous Thromboembolism in Multiple Myeloma Patients across Different Regimens: Role of Procoagulant Microparticles and Cytokine Release

Neutrophil Extracellular Traps (NETs) and Hypercoagulability in Plasma Cell Dyscrasias—Is This Phenomenon Worthy of Exploration?

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