Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors

Abstract

Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.

Navigating through the haemostatic paradox in kidney failure: A practical overview

“…This indicates a hypo‐fibrinolytic state and pro‐thrombotic risk. Pavlou et al 21 also found pre‐HD PAI levels to be much greater than those of the normal cohort. PAI levels decreased post‐HD but remained significantly greater than those of the controls.…”

“…Nonetheless, this study concluded that both factors increase greatly and uniformly with HD and HDF. Pavlou et al 21 measured several coagulation factors pre‐ and post‐HD. Pre‐HD, fibrinogen, FXIII, VWF and FVIII levels were much greater than those of the normal population and further increased post‐HD.…”

“…Increased risk of thrombotic events is also attributed to enhanced platelet phospholipid bilayer scrambling, where the procoagulant phospholipids PS and phosphatidylethanolamine (PEA) become exposed to the extracellular space (Figure 1). 20,21 …”

Red Blood Cell Abnormalities as the Mirror of SARS-CoV-2 Disease Severity: A Pilot Study

“…Intracellular ROS (iROS) and calcium (iCa 2+ ) levels were measured by flow cytometry as previously described ( Pavlou et al, 2021 ). For the detection of cleaved caspase-3 (RBC caspase-3), red blood cells were washed three times with phosphate-buffered saline solution (PBS) and were resuspended in PBS at a concentration of 4% Hct.…”

A Review on Electrospun Poly(amino acid) Nanofibers and Their Applications of Hemostasis and Wound Healing

“…Avoiding the serious consequences caused by excessive blood loss and wound infection has always been the focus of clinical medical research. It can be seen from the above that electrospinning nanofibers are a good choice with structural and performance advantages [ 130 , 131 , 132 , 133 , 134 ]. Electrospinning of poly(amino acids) with high biocompatibility and loading of drugs or active substances with anti-inflammatory, antibacterial, and hemostatic functions can obtain electrospun nanofibers with good medical effects and sustained drug release therapeutic effects [ 135 , 136 , 137 , 138 , 139 ].…”