[Show abstract][Hide abstract] ABSTRACT: Thrombomodulin (TM) serves as the endothelial cell receptor for thrombin and alters its characteristics from pro- to anticoagulant. Additionally, it promotes the formation of activated protein C. We evaluated the conservation of the overall outcome of these functions in recombinant TM linked to artificial surfaces by incubation with human whole blood in vitro. TM was covalently immobilized through poly(ethylene glycol) (PEG) spacers onto thin films of poly(octadecene alt maleic anhydride) covering planar glass substrates. TM binding to the polymer films was achieved after active ester formation at the carboxylic acid terminus of the PEG spacers and thoroughly characterized by HPLC-based amino acid analysis, immunofluorescence and ellipsometry. TM-coated samples were incubated for 3h with freshly drawn whole human blood anticoagulated with heparin (5IU/ml) using in-house developed incubation systems. The substantially reduced activation of blood coagulation (TAT) for TM-coated samples correlates well with the degree of contact activation (bradykinin and FXIIa formation) while no significant effects were observed for the platelet activation (PF4). Further, complement activation (C5a levels), was strongly diminished at the TM-containing surfaces. We conclude that the suggested method for preparation of TM immobilization may serve to prepare model substrates for studies on TM interactions but similarly provides a promising coating strategy for blood contacting medical devices.
[Show abstract][Hide abstract] ABSTRACT: To review the perioperative management of antithrombotic therapy in cardiac surgery, including the management of cardiopulmonary bypass (CPB) and off-pump surgery.
A review of the relevant English literature over the period 1975-2005 was undertaken, in addition to a review of international practices in antithrombotic therapy in cardiac surgery.
Cardiopulmonary bypass is required in most procedures and makes anticoagulation mandatory. Anticoagulation is, usually, achieved with unfractionnated heparin (UFH). Unfractionated heparin is monitored by point-of-care (POC) testing, such as the activated clotting time or the determination of heparin concentration. The target values of both tests remain empirical, with no clearly validated thresholds. The target value needs to be adjusted according to the POC test, given significant variations between devices and activators. After CABG, the need for antiplatelet therapy is well demonstrated, in order to limit the risk of postoperative death or ischemic events, and improve venous graft patency. Immediately after valvular surgery, antithrombotic therapy should take into account the specific risk carried by each patient and by each prosthetic device. The risk of venous thromboembolism, though poorly defined, is also present in the postoperative period and may require additional attention. Given the frequent exposure to UFH, occurrence of heparin-induced thrombocytopenia is not infrequent in these patients and requires careful individual management.
Antithrombotic therapy is an essential component of cardiac surgery. Yet, with the exception of antiplatelet agents in CABG patients, antithrombotic therapy is often based on the clinical experience of medical teams more than on an evidence-based assessment of the literature.
Canadian Journal of Anaesthesia 07/2006; 53(6 Suppl):S89-102. · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary artery bypass grafting (CABG) today results in what may be regarded as acceptable levels of blood loss with many institutions avoiding allogeneic red cell transfusion in over 60% of their patients. The majority of cardiac surgeons employ cardiotomy suction to preserve autologous blood during on-pump coronary artery bypass surgery; however the use of cardiotomy suction is associated with a more pronounced systemic inflammatory response and a resulting coagulopathy as well as exacerbating the microembolic load. This leads to a tendency to increased blood loss, transfusion requirement and organ dysfunction. Conversely, the avoidance of cardiotomy suction in coronary artery bypass surgery is not associated with an increased transfusion requirement. There is therefore no indication for the routine use of cardiotomy suction in on-pump coronary artery surgery.
Journal of Cardiothoracic Surgery 02/2007; 2:46. · 0.90 Impact Factor
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