Aprotinin modulation of platelet activation in patients undergoing cardiopulmonary bypass operations

Primack, Craig; Walenga, Jeanine M.; Koza, Michael J.; Shankey, T. Vincent; Pifarré, Roque

doi:10.1016/0003-4975(96)00016-1

Cited by 35 publications

(8 citation statements)

References 13 publications

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“…This suggests that platelets maintain their potential activity and that platelet function is not completely shut down. The small aggregates of platelets may be activated by additional triggers such as increased shear stress (20,21), activated leukocytes (22,23), and activated complements (22), resulting in the development of irreversible macroaggregation (macroaggregation is essential for primary thromboembolism because it gives strength to the platelet plug). If so, the increased number of small aggregates may lead to the occurrence of a thromboembolic accident during mechanical support.…”

Section: Discussionmentioning

confidence: 99%

Platelet Damage Caused by the Centrifugal Pump: Laser‐Light Scattering Analysis of Aggregation Patterns

Tanaka¹,

Kawahito²,

Adachi³

et al. 2001

Artificial Organs

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Platelets are damaged by shear force during centrifugal pumping; however, the mechanism of this damage has not been fully investigated. A new laser-light scattering (LS) assay method enables quantification of real-time changes in the number of platelet aggregates of different sizes. Using this method, we assessed the kinetics of platelet damage caused by the centrifugal pump from the standpoint of platelet aggregation capacity. Conventional optical density (OD) and LS methods were used to measure platelet aggregation with a Kowa AG-10 aggregometer. Platelet aggregation in fresh human blood was evaluated in a mock circuit for 3 h under a flow rate of 5.0 L/min and a pressure head of 100 mm Hg. Test samples were obtained before pumping for control, and at 1, 2, and 3 h after the start of pumping. The test series was begun 8 times. Aggregation after stimulation by 2.0 microg/ml collagen was determined; small (9 to 25 microm), medium (25 to 50 microm), and large (50 to 70 microm) aggregates were counted by the LS method. OD measurement at hourly intervals showed significant reduction in platelet aggregation. The LS method showed that generation of small and medium aggregates was not suppressed during pumping, but that generation of large aggregates was significantly reduced at 2 and 3 h of pumping. Platelet aggregation is significantly suppressed during centrifugal pumping, and the resulting platelet dysfunction is due mainly to inhibited development of small aggregates into larger aggregates.

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Section: Discussionmentioning

confidence: 99%

Platelet Damage Caused by the Centrifugal Pump: Laser‐Light Scattering Analysis of Aggregation Patterns

Tanaka¹,

Kawahito²,

Adachi³

et al. 2001

Artificial Organs

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“…204-207 It is more relevant to the present discussion that aprotinin is not simply an antifibrinolytic agent, but is also a polyvalent enzyme inhibitor of many of the enzymes involved in inflammation.2°8 Through this mechanism, aprotinin is an effective antiinflammatory agent, modulating leukocyte and platelet activation, in addition to platelet-platelet and especially leukocyte-platelet interactions. 209 Because of these properties, aprotinin may be considered a first-line modality in reducing the occurrence and morbidity of the postpump inflammatory syndrome.…”

Section: Mechanical Anti-inflammatory Measuresmentioning

confidence: 99%

Inflammation After Cardiopulmonary Bypass: Therapy for the Postpump Syndrome

Hennein

2001

Semin Cardiothorac Vasc Anesth

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Cardiopulmonary bypass (CPB) is used in most, but not all, complex heart operations. CPB is associated with a systemic inflammatory response in adults and children. Many materials-dependent (exposure of blood to nonphysiologic surfaces and conditions) and materials-independent (surgical trauma, ischemia-perfusion to the organs, changes in body temperature, and release of endotoxin) factors during CPB have been implicated in the etiology of this complex response. The mechanisms involved may include complement activation, release of cytokines, leukocyte activation with expression of adhesion molecules, and production of various vasoactive and immunoactive substances. Postpump inflammation may lead to postoperative complications and may result in respiratory failure, renal dysfunction, bleeding disorders, neurologic dysfunction, altered liver function, and ultimately multiple organ failure. Significant efforts are being made to decrease the generation and effects of postpump inflammation. Interventions to this end have included avoiding CPB when possible, improving the biocompatibility of the involved mechanical devices, and administering medications that maintain cellular integrity. This article provides an overview of the etiology, pathophysiology, and treatment of postpump inflammation. Perhaps with additional insight into this syndrome, CPB can be made a safer and more efficacious modality of cardiorespiratory support. Copyright© 2001 by W.B. Saunders Company.Gardiopulmonary bypass (CPB) is an indispensable modality used in most, although not all, complex heart operations. However, CPB is associated with a systemic inflammatory response that occurs in both adults and children.2-8 Many factors during CPB, either dependent on materials (exposure of blood to nonphysiologic surfaces and conditions) or independent of materials (surgical trauma, ischemia-perfusion to the organs, changes in body temperature, and release of endotoxin), have been implicated in the etiology of this complex response. The mechanisms involved may include complement activation, release of cytokines, leukocyte activation with expression of adhesion molecules, and production of various vasoactive and immunoactive substances, including oxygen free radicals, arachidonic acid metabolites, platelet-activating factor (PAF), nitric oxide (NO), and endothelins. Postpump inflammation may lead to postoperative complications and, in the extreme, may result in respiratory failure, renal dysfunction, bleeding disorders, neurologic dysfunction, altered liver function, and ultimately multiple organ failure (MOF).Significant efforts are being made to decrease the generation and effects of postpump inflammation. Interventions to this end have included avoiding CPB when possible, improving the biocompatibility of the involved mechanical devices, and administrating medications that maintains cellular integrity. This article provides an overview of the etiology, pathophysiology, and treatment of postpump inflammation. Perhaps with additional insight into thi...

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“…All of these factors may contribute to the potential usefulness of aprotinin in abciximabtreated patients. [66][67][68] Aprotinin and the lysine analogs have demonstrated efficacy in reducing blood loss and transfusion requirements in patients undergoing CABG surgery; however, their role in abciximabtreated patients requires further study.…”

Section: Options For Minimizing Bleeding Riskmentioning

confidence: 99%

Management of Antiplatelet Therapy for Minimization of Bleeding Risk Before Cardiac Surgery

2006

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Antiplatelet therapy is commonly administered for primary and secondary prevention of stroke, recurrent angina, myocardial infarction, and death in patients with cardiovascular disorders. It also is associated with an increased risk of bleeding. We describe the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery. In addition, we provide basic information about the mechanisms of action by which the most common antiplatelet agents inhibit platelet function. This information is integrated with results from pharmacologic studies and clinical trials. Determining the net effect in patients undergoing coronary artery bypass graft surgery requires knowledge about the pharmacokinetics, pharmacodynamics, and clinical efficacy of each drug, and an estimation of the absolute thrombotic versus hemorrhagic risk for each patient.

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Aprotinin modulation of platelet activation in patients undergoing cardiopulmonary bypass operations

Cited by 35 publications

References 13 publications

Platelet Damage Caused by the Centrifugal Pump: Laser‐Light Scattering Analysis of Aggregation Patterns

Platelet Damage Caused by the Centrifugal Pump: Laser‐Light Scattering Analysis of Aggregation Patterns

Inflammation After Cardiopulmonary Bypass: Therapy for the Postpump Syndrome

Management of Antiplatelet Therapy for Minimization of Bleeding Risk Before Cardiac Surgery

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