High Levels of β2-Microglobulin May Impact Coagulation Function in Patients With NDMM

Multiple myeloma (MM) is one of the most prevalent hematological malignancies affecting thousands of patients across the globe and is expected to impact nearly 36,000 individuals in the US in 2024.¹ It is characterized by the malignant proliferation of plasma cells and non-functional monoclonal immunoglobulins (M protein), which can often lead to coagulation dysfunction.² Researchers from multiple institutions in China identified the multifaceted link between MM and coagulation dysfunction, finding that increased thrombin generation, invasion of blood vessel walls by myeloma cells, and interference by M protein collectively contribute to a hypercoagulable state in patients with newly diagnosed (ND) MM.

Monitoring coagulation abnormalities and specific M protein types in patients with NDMM can aid in identifying patients with a higher risk for coagulation dysfunction. Image Credit: © tonstock - stock.adobe.com

Coagulation dysfunction is the leading cause of death in patients with MM, severely impacting prognosis, treatment, and management of comorbidities, and is directly related to the pathophysiology of the disease. MM cells invade the blood vessel wall and metastasize to other tissues, causing the blood vessel wall to release procoagulant factors and endothelial cell damage. Endothelial cell damage causes the release of a large amount of tissue factor, which activates the coagulation system and disrupts normal blood clotting and breakdown processes in patients. Prior studies suggest that coagulation alterations in MM patients could be related to M protein interference with the formation of fibrin fibers, which are critical for effective clotting and wound healing.²

The researchers investigated the coagulation function at different stages among different M protein types, as well as the association with β2-microglobulin (β2-MG). According to other studies, β2-MG, a small molecule protein responsible for aiding immune function, is closely related to M protein and may be an effective early marker of coagulation disorders.²

The study explored the changes in coagulation function under different conditions and their correlation with β2-MG in 371 NDMM patients and 48 healthy controls. Baseline data collected included β2-MG and various coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), fibrinogen degradation products (FDP), and D-dimer (D-D). The researchers divided the patients into different groups based on the Durie-Salmon staging system (DS), the International Staging System (ISS), and M protein type disease classification. These indices were compared among the groups and the correlation between each index and β2-MG was analyzed.²

The results showed that levels of PT, FIB, TT, FDP and D-D in the MM group were significantly higher (all P < .001) compared with the healthy control group. Further, as DS and ISS staging increased, coagulation indexes also increased significantly (all P < .001). The authors observed a positive correlation between β2-MG and PT, TT, and FDP levels (Spearman r = 0.157, 0.270, 0.108, respectively; all P < .05), and a negative correlation with FIB (r = −0.220, P < .001). This indicates that higher β2-MG levels are associated with prolonged clotting times and increased fibrin degradation, while lower β2-MG levels are linked to higher fibrinogen levels.²

The authors suggest that NDMM with light chain M protein should be treated with anticoagulants to prevent thrombosis, and patients with intact M protein should receive plasma products to prevent bleeding. Based on their findings, monitoring coagulation abnormalities and specific M protein types in patients with NDMM can aid in identifying patients with a higher risk for coagulation dysfunction, providing patients with appropriate intervention strategies and improved outcomes.

REFERENCES

1. The evolving treatment landscape of multiple myeloma: gprc5d-targeted car t-cell therapy. Pharmacy Times. July 2, 2024. Accessed July 23, 2024. https://www.pharmacytimes.com/view/the-evolving-treatment-landscape-of-multiple-myeloma-gprc5d-targeted-car-t-cell-therapy

2. Hu M, Ma Y, Jia K, et al. Analysis of coagulation alteration and its correlation with β2-microglobulin in 371 patients with newly diagnosed multiple myeloma. Hematology. July 12, 2024. doi:10.1080/16078454.2024.2377849