Microparticles in sickle cell anaemia: promise and pitfalls

Abstract

Blood from patients with sickle cell disease contains microparticles (MP) derived from multiple cell sources, including red cells, platelets, monocytes and endothelial cells. MPs are of great interest because of their disease associations, their status as promising biomarkers, and the intercellular communications they mediate. To illustrate the likelihood of their relevance in sickle cell disease, we discuss the nature of MP, their profiling in sickle disease, some caveats relevant to their detection, their roles in supporting coagulation and the disparate influences they may exert upon the pathobiology of sickle cell disease.

Differences of microparticle patterns between sickle cell anemia and hemoglobin SC patients

“…Furthermore the pre-analytical and analytical procedures that we used were also different. These two technical steps are well known critical factors impacting MP pattern, quantitatively and qualitatively [26]. Despite undertaken standardization attempts [51,52], no consensus for flow-cytometry analysis of MPs has emerged up to now [26] leading to different protocols and doubts on the most accurate strategy to be used.…”

“…Indeed, it has been shown that MPs originated from sickle RBCs may trigger coagulation, increase the production the production of radical oxygen species by endothelial cells, induce erythrocyte adhesion to endothelial cells and endothelial cell apopotosis, as well as, trigger renal vaso-occlusive crisis in a sickle mouse model [24–26]. Furthermore, several studies also supported a role of MPs in the occurrence of several complications in patients with SCA [15,27–28].…”

Intravascular hemolysis and the pathophysiology of sickle cell disease

“…This is also correct. Published data evidence the involvement of oxidative stress (79,100,105,108,113,115,116,121,123,132,134,135), inflammation (9, 22, 27, 32, 101, 105-108, 115, 124-127, 134), dyslipidemia (135)(136)(137)(138), microparticles (89,122,123,139), and vasoactive peptides (110,111,(140)(141)(142)(143). These additional pathways (depicted in Figure 2) are potentially additive or synergistic to intravascular hemolysis-like mechanisms.…”

“…Ferric and ferryl forms of hemoglobin produced in SCD and other forms of hemolysis are highly reactive in promoting oxidation (119)(120)(121). Hemolysis also produces red cell microparticles that can deliver toxic heme to endothelial cells (122,123). Heme species appear to activate innate immune sterile inflammation pathways through TLR4 and NALP inflammasome signaling (104,105,124,125).…”

Sickle cell disease: a malady beyond a hemoglobin defect in cerebrovascular disease

“…In addition, immunologic or genetic interventions targeting endothelial protein C receptor (EPCR), activated protein C (APC), or thrombin also blunted the enhanced microvascular thrombosis [50]. Furthermore, microparticles (MPs) derived from RBCs and platelets may also influence SCD pathobiology especially maintaining its hypercoagulable state through activation of FXI dependent coagulation pathways [97]. …”