Activation of platelets and coagulation during haemodialysis

In end-stage kidney disease, haemodialysis treatment is applied to remove excess fluid and waste products, such as urea and creatinine, from the blood. In this thesis, attention is focussed on activation of platelets and the coagulation system using several types of dialyzer membranes. A variety of parameters regarding platelet morphology, platelet activation, platelet degranulation and markers for activation of coagulation were investigated both before and during haemodialysis treatment with different dialyzer membranes. With regard to endothelial cell activation, the biomarker proendothelin-1 was investigated together with activation of the coagulation system and platelet granule depletion.
Already before the start of a haemodialysis session patients have a low normal platelet count and a reduced staining density of the platelet granule content. Also, platelet surface expression of p-selectin is absent. Results may reflect impaired megakaryopoiesis. The chronic depletion of granule content is most likely due to repeated platelet activation during the haemodialysis treatment. After a haemodialysis session a slight decrease in PLT count is observed, which is probably a result from adherence to the dialyzer membrane and a decreased influx from the storage pools.
Prior to a haemodialysis session patients already reveal an activated coagulation system. During a session, extensive activation of the coagulation system is observed in spite of the anticoagulant regime and the relative bio-compatibility of the dialyzer membranes. Activation of the coagulation system seems to be especially initiated via the factor XII dependent pathway. Some evidence of an impaired integrity of the endothelium was obtained.