Bradykinin production during donor plasmapheresis procedures

Abstract

Extracorporeal circuits made of artificial substances may induce blood cells and humoral activation. Negatively charged surfaces may activate Factor XII and the prekallikrein-kinin cascade, resulting in bradykinin (BK) production. BK has been considered to be involved in severe hypotensive reactions occurring during therapeutic apheresis in patients taking angiotensin-converting enzyme (ACE) inhibitors or in those receiving platelet transfusion. In this study we investigated BK production during donor plasmapheresis procedures. Eighteen volunteer donors entered the study protocol. Nine of them were taking ACE inhibitors. Their blood pressure (BP) was monitored both pre- and post-apheresis, and BK determination was carried out using a competitive enzyme immunoassay (EIA), in plasma samples collected both during and at completion of the procedure. In addition, a limited number of thawed plasma units were checked for BK. No side-effects were observed during the procedures. However, donors taking ACE inhibitors showed a higher variation of their systolic BP compared to those who were not taking ACE inhibitors, while diastolic BP percentage variations did not differ significantly between the two groups. The BK concentration was considerably higher in donors taking ACE inhibitors: 183 +/- 26 versus 82 +/- 6 ng/ml (P < 0.0001) after the first collection cycle and 142 +/- 20 versus 65 +/- 11 ng/ml (P < 0.0001) in the final samples. BK was also detected, at a lower concentration (15 ng/ml), in one out of four thawed plasma units obtained from donors taking ACE inhibitors and at 1 ng/ml in one out of two thawed plasma units from the control group. Donors taking ACE inhibitors and undergoing plasmapheresis showed higher levels of BK compared to the control group. Furthermore, the detection of BK in plasma units after a freeze-thaw procedure might explain the sudden hypotensive reaction occurring during therapeutic plasma exchange when plasmapheresis units are adopted as substitution fluids. Further investigations are needed to assess the real clinical importance of the presence of BK in plasma units.