Platelet reactivity in patients with chronic kidney disease and hemodialysis

Mourikis, Philipp; Helten, Carolin; Dannenberg, Lisa; Hohlfeld, Thomas; Stegbauer, Johannes; Petzold, Tobias; Levkau, Bodo; Zeus, Tobias; Kelm, Malte; Polzin, Amin

doi:10.1007/s11239-019-01983-x

Cited by 10 publications

(9 citation statements)

References 18 publications

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“…PLT activation might happen during the dialysis session [ 44 ]; however, dialysis often reduces the PLT activation markers [ 44 , 45 ]. This was also observed in our patients through decrease in the CD62P + PLTs, as a probable result of HD-induced cell clearance [ 46 ] or increased microvesiculation [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Similar trends were observed against HD Vintage, with increasing PAF RNA, PPBP synthesis, and platelet MMP1 and TIMP2 secretion over time. Thus, while coagulative reactivity has been shown to remain consistent throughout individual HD sessions 48 , platelet behaviors beyond coagulation may naturally change with longer prior time on dialysis, and increasing BFR may exacerbate pathogenesis by accentuated repetitive and excessive stimulation of platelets during therapy. Chronic change in platelet function considering no acute change in coagulation may in part be explained by receptor shedding, given long-term accumulation of MMPs in spite of intra-HD clearance 49 .…”

Section: Discussionmentioning

confidence: 99%

Hemodialysis Exacerbates Proteolytic Imbalance and Pro-fibrotic Platelet Dysfunction

Velasquez-Mao

Velasquez

Hui

et al. 2021

Preprint

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Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation. Basal plasma levels of proteolytic regulators and fibrotic factors were elevated in ESRD patients compared to healthy controls, with isoform-specific changes during HD. Platelet lysate (PL) RNA transcripts for growth and coagulative factors were elevated post-HD, with upregulation correlated to HD vintage. Platelet secretome correlations to plasma factors reveal acutely induced pro-fibrotic platelet phenotypes in ESRD patients during HD characterized by preferentially enhanced proteolytic enzyme translation and secretion, platelet contribution to inflammatory response, and increasing platelet dysfunction with blood flow rate (BFR) and Vintage. Compensatory mechanisms of increased platelet growth factor synthesis with acute plasma matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) increases show short-term mode-switching between dialysis sessions leading to long-term pro-fibrotic bias. Chronic pro-fibrotic adaptation of platelet synthesis were observed through changes in alpha-granule- and lysosome-filling behaviors. We conclude that chronic and acute platelet responses to HD contribute to a pro-fibrotic milieu in ESRD.

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“…The common thread between dialysis patients and COPD patients is the existence of chronic systemic inflammation implicated in the development of cardiovascular disease. In response to inflammation, it is well known that platelets in COPD and dialysis patients are activated in the bloodstream, altering their hemostatic properties [16][17][18][19] and therefore the process of adhesion and aggregation.…”

Section: Discriminating Parameters and Pathology Testmentioning

confidence: 99%

Personalized pathology test for Cardio-vascular disease: Approximate Bayesian computation with discriminative summary statistics learning

et al. 2022

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Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment.

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Platelet reactivity in patients with chronic kidney disease and hemodialysis

Cited by 10 publications

References 18 publications

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

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

Hemodialysis Exacerbates Proteolytic Imbalance and Pro-fibrotic Platelet Dysfunction

Personalized pathology test for Cardio-vascular disease: Approximate Bayesian computation with discriminative summary statistics learning

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