Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility?

Background. The sum of undesirable side effects, occurring during haemodialysis (HD), is called bioincompatibility. Concerning platelets, both an increase in the expression of the cell surface marker Pselectin (CD62p) and release of the intracellular granule product platelet factor 4 (PF4) have been described. However,asPF4isalsoabundantlypresentonendotheliumbound proteoglycans, it is questionable whether the HDinduced increase is exclusively attributable to release from platelets. With respect to the cause of HD-induced bioincompatibility, interest has been focused mainly on the extracorporeal circuit (ECC), especially the dialyser, whereas only little attention has been paid to other parts of the ECC and the mode of anticoagulation applied. To address the cause and origin of platelet activation and PF4 release during clinical HD, two complementary clinical studies were performed. Materials and methods. In study I, the relative influence of the various parts of the ECC was evaluated by measuring the expression of CD62p, platelet aggregation and levels of PF4 and serotonin at various sampling points. In study II, low-molecular-weight heparin (LMWH) was administered 10 min before the actual start of HD, in order to separate the effects from LMWH and the ECC on platelet activation. Results. In study I, CD62p expression increased across the entire length of the ECC, including the roller pump and dialyser (median at t5 from 26% to 43%, P = 0.008; median at t30 from 28% to 48%, P = 0.007). Increments in PF4 and aggregation of platelets were relatively modest. Platelet serotonin content, which was below reference values in healthy controls, and plasma serotonin concentration, which was above reference values, did not change. In study II, PF4 levels increased markedly after the injection of LMWH (from 12 IU/ml at t−10 to 75 IU/ml at t0, P = 0.018), whereas CD62p expression remained stable until the start of HD.