fig1

Figure 1. Hypothetical mechanism of bleeding and thrombotic risks in patients undergoing hemodialysis. Platelets become activated upon entering the hemodialysis circuit, either losing their granule content and becoming exhausted or aggregating with activated polymorphonuclear neutrophils. These aggregates carry oxidative stress and inflammatory mediators, which are transported to the hematopoietic niche in the lungs, skewing the differentiation of hematopoietic stem cells (HSCs) and megakaryocytes (MgKs) toward biologically aged phenotypes. Aged HSCs and MgKs directly impact thrombopoiesis or indirectly prime platelets to become more sensitive to activation stimuli through the senescence-associated secretory phenotype (SASP) and other proinflammatory signaling in the presence of aged leukocytes. These hyperactive platelets re-enter the HD circuit, creating a positive feedback loop that increases inflammatory cytokines and oxidative stress, which are once again delivered to the lungs. The balance between naïve, activated, and exhausted platelets is maintained by homeostatic buffering mechanisms. However, when this vicious cycle sustains chronic inflammation in vessel walls, it may promote atherothrombosis. Alternatively, if this process leads to significant qualitative changes in platelets or a depletion of thrombopoietic capacity, the prevalence of exhausted platelets could increase bleeding risk. The bold arrows indicate cell dynamics while the dotted arrows represent their functional properties. HSC: Hematopoietic stem cell; HD: hemodialysis; MgK: megakaryocyte; MNC: mononuclear cell; PMN: polymorphonuclear cell; SASP: senescence-associated secretory phenotype.