Abstract
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.
Highlights
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]
The interaction between FXII and neutrophil extracellular traps (NETs) is not limited to only a one-way effect; Stavrou et al found that FXII together with zinc (Zn2+ ) promoted citrullination of histone H3, and the pathway that involves the binding of FXII to urokinase plasminogen activator receptor triggered deoxyribonucleic acid (DNA) release from the cell [36]
Both these agents induced the release of murine NETs and citrullination of histones, which proves that multiple myeloma cells and their products act through activation of peptidyl arginine deiminase 4 (PAD4)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Patients diagnosed with MGUS do not present symptoms of organ damage typical in multiple myeloma; monoclonal protein of less than 30 g/L can be found in their serum [2,4]. There are established criteria for organ injury in the course of multiple myeloma (SLiM CRAB), and they include serum Calcium concentration >2.75 mmol/L, Renal insufficiency with creatinine serum concentration. Renal insufficiency that arises in the course of plasma cell dyscrasias (as stated in SLiM CRAB criteria) results from various pathologies:. Increased serum protein concentration that occurs in plasma cell dyscrasias and contributes to renal insufficiency entails the risk of developing hyperviscosity syndrome. This is triggered by hyperproteinemia, causing an impairment in blood flow in the microvasculature. Along with neurological manifestation and retinal changes caused by insufficient blood flow, hyperviscosity may induce vein thrombosis [4]
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