Background. The contact system is generally believed to be the main trigger
of the coagulation cascade during extracorporeal circulation. However, the
extent of contact activation, its role for intradialytic thrombin generati
on as well as the influence of different dialyzer membranes have not been w
ell established.
Methods. In a novel full-scale ex vivo recirculation dialysis model, we inv
estigated the thrombogenicity of three widely used hemodialyzers (Cuprophan
Renak RA 15-U, Polysulfone F6HPS and AN69XT Nephral 200). The activation o
f the contact system was evaluated using a newly developed ELISA for factor
XIIA- CI-inhibitor complexes. Additionally. we determined free FXIIa (ELIS
A), thrombin-antithrombin (TAT) complexes, platelet factor 4 (PF4), complem
ent activation (C5a), granulocyte elastase and blood cell counts. The findi
ngs in blood from normal volunteers were compared with factor XII-deficient
blood.
Results. With normal blood AN69 exhibited the highest thrombogenicity in co
mparison to Cuprophan and Polysulfone, as assessed by TAT generation and pl
atelet consumption. AN69 caused a rapid increase of the FXIIa-C1-inhibitor
complexes and of free FXIIa. Despite significant TAT generation with Cuprop
han and Polysulfone free FXIIa remained unchanged and the FXIIa-C1-inhibito
r complexes stayed below the detection limit. With factor XII-deficient blo
od Polysulfone exhibited the same TAT generation, whereas the thrombogenici
ty of AN69 was greatly reduced.
Conclusions. Our data challenge the common assumption that activation of th
e contact system with generation of FXIIa is the main trigger for coagulati
on and thrombus formation in hemodialysis. Only the negatively charged AN69
membrane with enhanced thrombogenicity strongly induced contact activation
.