Kinetics of Bradykinin Levels during and after Leucocyte Filtration of Platelet& ;Concentrates

Abstract

Objective: To measure beadykinin levels in platelet concentrates during and after leucocyte filtration. Methods: Platelet concentrates were leukocyte depleted using three different leucocyte-depletion filters selected to represent filters with negative, positive or neutral charge, respectively. Bradykinin levels were analysed before, during and up to 90 min post-filtration. Results: Significant levels of bradykinin were generated when negatively charged leucocyte depletion filters were used. However, we found a high variation between platelet concentrates prepared from different donors as well as within the same concentrate when this was divided into three aliquots. Generated bradykinin was rapidly degraded in the collection bag and no bradykinin was detectable 60 min post-filtration. Conclusion: Bradykinin generation is more pronounced when negatively charged leucocyte removal filters are used. Due to a rapid degradation of bradykinin in the storage bag, pre-storage filtration should minimise the risk of bradykinin related adverse reactions during transfusion with some filters.

Safety and tolerability of a modified filter‐type device for leukocytapheresis using ACD‐A as anticoagulant in patients with mild to moderately active ulcerative colitis. Results of a pilot study

“…The analyses were made during the first session. All measured concentrations of bradykinin were less than levels reported with filter devices as previously seen by Iwama [12] and Hild et al [13]. Fig.…”

“…Negatively charged surfaces can activate Factor XII and the prekallikrein-kinin cascade, resulting in bradykinin generation with risks of severe hypotensive reactions, especially in patients on angiotensin-converting enzyme inhibitor treatment. It is well known that negatively charged filters are associated with higher risks for bradykinin generation [12][13][14]. The Cellsorba TM EX global type has been developed from Cellsorba E used in Japan for intended use with ACD-A as anticoagulant.…”

Selection of Anticoagulants for Leukocytapheresis Therapy in Cases of Active Ulcerative Colitis

“…A biological material with a negative charge on its surface will activate blood coagulation factor XII, which induces the coagulation cascade, producing the strong vasodilator, bradykinin [5,6] . Bradykinin is rapidly degraded and inactivated by kininase II in the blood, but reports indicate possible side effects, including fall of blood pressure due to increased bradykinin concentrations arising from inhibition of kininase II in patients taking angiotensin-converting enzyme inhibitors.…”

“…NM alone (30-50 mg) or LMWH + NM (1 mg) inhibited bradykinin production, whereas heparin alone or LMWH alone significantly accelerated it. However, an excessive fall of blood pressure was not noted in any generated when blood or plasma passes through negatively charged filters [5,6] . The anticoagulant nafamostat mesilate (NM) has been reported to almost completely suppress the rise of bradykinin levels [6] .…”

Reduction in bradykinin generation during leukocytapheresis using novel cellsorbaTM CS‐180S: Effects of changing the filling solution

“…The surfaces of the nonwoven fiber of the Cellsorba TM filter, with which LCAP is performed, are negatively charged. The risk of generating bradykinin is high with the negatively charged filters [6][7][8] On the other hand, there have been several reports that repeated administration of NM causes the generation of anti-NM IgE antibodies [9], which results in allergy-like symptoms such as nausea, headache, fever, tongue and lip numbness, general malaise, and mild dyspnea [10]. Since NM is generally used for LCAP as anticoagulant, this issue is very important.…”