Differences in biocompatibility of various hemodialysis membranes cause different degrees of complement activation, leukopenia, and hypoxemia during hemodialysis. In order to further clarify the complex sequence of activation of complement, leukopenia and dialysis hypoxemia, we followed leukocyte count and arterial oxygen tension in 23 patients during two successive dialyses using membranes based on regenerated cellulose (RC) and cellulose acetate (CA). In 12 of the patients, signs of complement activation were investigated by following changes in arterial levels of total hemolytic complement, plasma C3d and C5a. Furthermore, C5a was determined in plasma from the dialyzer effluent line. The study demonstrates basic differences in biocompatibility of the two membranes: hemodialysis using RC membranes was associated with more pronounced leukopenia and hypoxemia than dialysis with CA membranes and, during dialysis using RC membranes, generation of C5a in the dialyzer was evident by demonstration of high values of this anaphylatoxin in dialyzer effluent plasma at the beginning of treatment with gradual decline towards detection limit at the end. Plasma C3d in arterial blood rose during dialyses with both RC and CA membranes, but significantly more with RC, suggesting that accumulation of this complement fraction may serve as a sensitive parameter for complement activation during hemodialysis.Our results suggest a pivotal role of C5a for hemodialysis-induced leukopenia and show that activation of complement, leukopenia, and arterial hypoxemia are interlinked membrane-dependent events.

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Protein C activity and antigen levels were determined in 10 haemodialysis patients and 10 healthy controls matched for age and sex. Markedly decreased protein C activity was found whereas protein C antigen level was normal in uraemics. This finding, together with our recent observation that plasma protein C activity is partly normalised during haemodialysis, lead us to suggest the presence of one or more inhibitors of protein C activity in plasma from patients with uraemia.

In order to elucidate the kinetics of haemodialysis-induced activation of complement, leucopenia and release of granulocyte-elastase, 10 patients (three females and seven males; mean age 47.8 years) were extensively studied during a 4 h haemodialysis treatment and for the following 24 h, and further compared with a healthy control group. Prior to dialysis patients had normal leucocyte count, plasma elastase bound to alpha 1-proteinase inhibitor (E-alpha 1P1) and total haemolytic complement, whereas plasma C3d was higher and plasma C5a lower than in controls. Haemodialysis induced initial leucopenia and subsequent rebound phenomenon lasting 24 h post treatment. These alterations were due to almost selective changes in neutrophile count as monocyte and lymphocyte counts, apart from decrease in the first 30 min, were unchanged. Total haemolytic complement decreased initially during dialysis and rose at the end. Generation of C5a within the dialyser was evident by demonstration of high levels of this anaphylatoxin in dialyser effluent plasma; maximal values observed coincided with the nadir of leukopenia. Plasma C3d and E-alpha 1P1 both progressively rose during dialysis. After termination of extracorporeal circulation the disappearance rates (T/2) were approximately 6 h and 2.5 h respectively. Haemodialysis thus induces changes in the complement and leucocyte system resembling an acute inflammation, which out-lasts the treatment period.

In a prospective study including 16 patients with multiple trauma and head injury and 14 patients with isolated head injury we measured plasma levels of prothrombin fragment 1 and 2 (F1 + 2) and thrombin/antithrombin III complex (TAT) on admission and on days 1, 2, 3, and 7 after the incident. On admission, all patients had values of F1 + 2 and TAT above the reference range. Admission levels of both F1 + 2 and TAT were significantly higher compared with levels on the following days. Admission levels of F1 + 2 was significantly correlated to the Injury Severity Score. TAT was higher in patients with multiple trauma than in patients with isolated head injury and were significantly correlated to the Injury Severity Score on admission and on day 3. Levels of F1 + 2 were significantly lower on day 1 in four patients with post-traumatic pulmonary dysfunction compared with patients without pulmonary dysfunction. With respect to levels of TAT, no differences were detected between patients with and without pulmonary dysfunction.