title: Aprotinin restores the adhesive capacity of dysfunctional platelets.
abstract: The post-operative coagulopathy associated with cardiopulmonary bypass (CPB) is known to be predominantly related to platelet dysfunction. The use of the serine protease inhibitor aprotinin dramatically reduces CPB associated hemorrhage and is thought to act primarily through the inhibition of plasmin without directly influencing platelets. Our data indicate that there is a direct effect of aprotinin on platelet adhesion, which has not been previously reported. We found that when aprotinin was added to blood samples with poorly adhesive platelets, platelet adhesion significantly increased as measured by the percent coverage of denuded arterial segments in the Baumgartner perfusion chamber. In preliminary experiments using expired platelet concentrates or fresh whole blood, the addition of aprotinin induced a positive increase of 22+/-7.5 and 14+/-6.2 percentage point in platelet adhesion, respectively. A simulated CPB model that recirculated a unit of anticoagulated whole blood for 2 h was used (n=14) to induce a platelet adhesion defect similar to that seen in clinical CPB. At initiation of recirculation, platelet adhesion was 55+/-9.5% but dropped to 13+6.5% coverage after 2 h simulated CPB. The addition of aprotinin to the post-recirculation samples induced a significant restoration of platelet adhesion back to 38+/-11% coverage. When epsilon amino-caproic acid with soybean trypsin inhibitor was added to post recirculation samples, there was no similar effect on adhesion scores. To compare these findings with surgical CPB, we collected one blood sample at the beginning and two at the end of CPB from each of seven open-heart patients. Aprotinin was added to one of each of the post-CPB samples. Platelet adhesion at the onset of surgical CPB was only 39+/-11% in this patient group but dropped to 7+/-7% by the end. Similar to the model, the addition of aprotinin post-CPB restored adhesion to 29+/-11%. These results suggest some action of aprotinin other than its antiplasmin effect, and that platelet adhesion in general can be promoted by aprotinin.
authors.affiliation: East Carolina University, School of Medicine, 213 Life Sciences Building, Greenville, NC 27858, USA. bradfieldj@mail.ecu.edu
authors.forename: John F
authors.initials: JF
authors.lastname: Bradfield
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Bode
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D007611:Aprotinin / Q000494:pharmacology*; D001158:Arteries / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004285:Dogs; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D023421:Models, Animal; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014841:von Willebrand Factor; D007611:Aprotinin