Reduction in Platelet Activation by Citrate Anticoagulation Does Not Prevent Intradialytic Hemodynamic Instability

Abstract

Background: The etiology of intradialytic hemodynamic instability is multifactorial. Of the various factors involved, a rise in core temperature seems to be crucial. In this respect, the bioincompatibility of hemodialysis (HD) treatment might play an important role. The application of cool dialysate reduces the number of periods of intradialytic hypotension (IDH) considerably. In rats, roller pump perfusion caused hypotension by shear stress induced platelet aggregation and subsequent serotonin release. During clinical HD, citrate anticoagulation abolished platelet activation almost completely. Hence, citrate anticoagulation might reduce IDH, whereas the beneficial effect of cool dialysate might be partly explained by reduced platelet activation. Methods: In the present study, blood pressure, IDH episodes, platelet activation, platelet aggregation, and serotonin release were studied crossover in 10 patients during HD with dalteparin anticoagulation at normal and low dialysate temperatures and during HD with citrate. Results: Citrate strongly reduced platelet activation, but did not improve IDH. The blood pressure was best preserved during cool-temperature HD, despite manifest platelet activation. Platelet activation was not accompanied by a rise in the plasma serotonin concentration. Conclusions: Three major conclusions can be drawn: (1) it is unlikely that platelet activation and subsequent serotonin release underlie IDH in the clinical situation; (2) the protective effects of cool dialysate on IDH appear to be independent of HD-induced platelet activation, and (3) extrapolating results from rat experiments to the human situation requires uppermost prudence.

Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

“…The latter agrees with the idea that degranulation of neutrophils is, at least partly, calcium dependent and independent of complement activation [10,12,14,18,20]. Our finding that citrate may cause less neutrophil degranulation by heparin during CVVH, is in concordance with studies during intermittent haemodialysis and a single study on CVVH [9,10,12,13,15]. The time course of the release of elastase and MPO seems to be dissimilar in our study, and release may be differently regulated.…”

Haemodialysis with Tinzaparin Versus Dialysate Citrate as Anticoagulation

“…This can be performed either by regional citrate [3] or by citrate containing dialysate that results in local anticoagulation [4,5]. The use of such anticoagulation has been suggested to limit the extent of platelets deposited on the surface of the dialyzer and to increase the patency of the dialyzer [6][7][8].…”

Coagulation activation, depletion of platelet granules and endothelial integrity in case of uraemia and haemodialysis treatment

“…Despite appropriate anticoagulation treatment, the rather unphysiological conditions within the ECC, amplified by pre-dialysis increased uraemia related factors, induce PLT activation. Increase of PLT activation and procoagulant activity is demonstrated in HD patients [24,25]. PLTs are activated within the ECC, as detected by increase in the expression of CD62p and release of β-tromboglobulin (β-TG) within the ECC [23].…”