Platelet hyperactivation in multiple myeloma is also evident in patients with premalignant monoclonal gammopathy of undetermined significance

O’Sullivan, L.; Meade-Murphy, Gerardene; Gilligan, Oonagh; Mykytiv, Vitaliy; Young, Paul; Cahill, Mary R.

doi:10.1111/bjh.16774

Cited by 13 publications

(10 citation statements)

References 68 publications

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“…Previous studies observed increased plasma levels of FVIII and VWF, increased activated protein C (APC) resistance and reduced soluble thrombomodulin levels in MM patients ( 25 ). Furthermore, patients with MM have more phosphatidylserine (PS) positive blood cells ( 26 ) and hyperactivation of platelets ( 11 , 27 ). Our study confirms that blood cells, especially RBCs and platelets, are crucial players in the disbalanced hemostasis in MM.…”

Section: Discussionmentioning

confidence: 99%

Patients With Multiple Myeloma Have a Disbalanced Whole Blood Thrombin Generation Profile

Roest

Sang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundMultiple myeloma (MM) is associated with a high prevalence of bleeding and an increased risk of thrombo-embolism. MM patients have reduced platelet- and red blood cell (RBC) numbers in blood, which may indicate that the paradoxical hemostasis profile is a consequence of a disturbed platelet and RBC homeostasis.ObjectivesTo get better insight in the disbalanced hemostasis of MM patients.MethodsWe conducted a case-control study on the whole blood (WB) coagulation profiles of 21 MM patients and 21 controls. We measured thrombin generation (TG) in WB and platelet poor plasma (PPP) of MM patients and controls.ResultsIn WB-TG, we observed that the median time to the thrombin Peak was 52% longer in MM patients than in controls, while the median endogenous thrombin potential until the Peak (ETPp) was 39% higher in MM-patients than in controls. In line with these findings, the levels of platelets, RBCs, white blood cells and agonist induced platelet activation were decreased in MM patients compared to controls. The plasma TG experiments showed no differences between MM-patients and controls.ConclusionPatients with MM have a disturbed blood cell metabolism and a disbalanced WB-TG profile. This disbalance may explain the paradoxically high prevalence of bleeding symptoms in MM patients vs. an increased thrombosis risk. There was no disturbance observed in plasma TG, indicating that blood cells are the major determinants for the disbalanced hemostasis in MM patients.

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Section: Discussionmentioning

confidence: 99%

Patients With Multiple Myeloma Have a Disbalanced Whole Blood Thrombin Generation Profile

Roest

Sang

et al. 2022

Front. Cardiovasc. Med.

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“…And IgG and IgA immunoglobulin can combine with coagulation factors or other plasma proteins in plasma, causing high viscosity at low concentration, thus inducing hemorrhage. In addition, M protein can cover platelets and coagulation factors and affect platelet aggregation, thus interfering with the normal coagulation process, resulting in abnormal coagulation [ 19 , 20 ].…”

Section: Discussionmentioning

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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“…Increased [9] Increased [9] NS [9] MV TF activity NS [9] Increased [9] Increased [9] cf DNA NS [9] Increased [9] NS [9] Platelet aggregation in PRP NS [37] NS [37] Decreased (except in ADP) [37] Platelet aggregation in washed platelets NS [38] NS [38] x P-selectin, CD63, Annexin V, PAC1 at resting Increased [8] NS [8] x P-selectin expression upon activation Decreased [8] NS [8] Decreased [37] Soluble GPVI levels NS [38] NS [8] NS [37] Circulating levels of PAC-1 and P-selectin NS [37] NS [37] x…”

Section: Evidence Of In Vitro Hypercoagulability In Mgus Patientsmentioning

confidence: 99%

“…On the other hand, biomarker studies suggest that there might be some shared biologic features between MM and MGUS responsible for the increased thrombotic risk, involving platelet activation and hypercoagulability [8,9]. Nevertheless, hemostatic abnormalities identified in MGUS patients lack correlation to clinical events and cannot be translated to clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Monoclonal Gammopathy of Thrombotic Significance

Gkalea

Fotiou

Dimopoulos

et al. 2023

Cancers

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The current review provides an overview of the thrombotic risk observed in patients with MG who do not otherwise require treatment. We discuss clinical and biomarker studies that highlight the heterogenous hemostatic profile observed in these patients and how knowledge has evolved over the past 20 years. Biomarker studies suggest shared biologic features between multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS), which involves both hypercoagulability and platelet activation. Hemostatic abnormalities identified in MGUS patients cannot be translated into clinical practice as they lack correlation to clinical events. The prothrombotic phenotype of MGUS patients has not been ascertained yet, but novel data on coagulation markers are promising. We also review rare conditions associated with the thrombogenic properties of the monoclonal protein that predispose to arterial, venous or microthrombotic events and demonstrate that the M-protein can be linked to clinically significant thrombotic events. Cryoglobulinemia, cryofibrinogenemia, cryo-crystaloglobulinemia and MG-related antiphospholipid syndrome are reviewed. We propose the new umbrella term “monoclonal gammopathy of thrombotic significance” (MGTS) to refer to significant, recurrent thrombotic events in patients with MGUS that provide a rationale for targeting the underlying plasma cell clone. Identifying MGUS patients at high risk for thrombotic events is currently a challenge.

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Platelet hyperactivation in multiple myeloma is also evident in patients with premalignant monoclonal gammopathy of undetermined significance

Cited by 13 publications

References 68 publications

Patients With Multiple Myeloma Have a Disbalanced Whole Blood Thrombin Generation Profile

Patients With Multiple Myeloma Have a Disbalanced Whole Blood Thrombin Generation Profile

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

Monoclonal Gammopathy of Thrombotic Significance

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