Endothelial protein C receptor expression after cardiopulmonary bypass in adult cardiac surgical patients
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KeywordsThrombin Cardiopulmonary Bypass Thrombin Generation Endothelial Activation Mild Hypothermia
Endothelial protein C receptor (EPCR) is a transmembrane glycoprotein primarily localised on vessel endothelium. EPCR binds protein C (PC) on the endothelial surface and presents it to the thrombin/thrombomodulin complex. Thrombin activates PC to APC, which exerts anticoagulant and anti-inflammatory effect. Proteolysis of membrane-bound EPCR releases soluble EPCR which can be detected in plasmatic circulation. This reaction indirectly correlates with thrombin generation and can be interpreted as marker of endothelial activation during cardiopulmonary bypass (CPB).
In a prospective study, the group of 35 adult patients (mean age 68 years) scheduled for cardiac surgery with standard cardiopulmonary bypass (duration 80 ± 30 minutes, heparin dose 3 mg/kg, mild hypothermia about 34°C) was evaluated. The markers of endothelial activation and coagulation parameters (EPCR, PAI-1, antithrombin, tPA, PTT, aPTT, fibrinogen, platelets and thromboelastography (TEG)) immediately before and after surgery were recorded. We hypothesized that the EPCR level (detected with ELISA monoclonal antibodies labeled with myeloperoxidase, 450 nm reader - detection limit 10 ng/ml soluble EPCR) increases after CPB and correlates with other markers of endothelial activation.
The cut-off value of EPCR was set down 200 ng/ml. In 17% of patients the value above the cut-off (366 ng/ml before, 209 ng/ml after CPB) was detected. The EPCR value decreases after CPB (150.7 ± 124 vs 99.4 ± 70.6) whereas tPA increases (1.5 vs 9.3 ng/ml) and PAI-1 was unchangeable. A trend to hypocoagulation after CPB was noticed (Δfibrinogen -1.04 g/l, ΔaPTT +7.7 sec, Δplatelets -67 G/l) but no correlation between EPCR and TEG parameters (coagulation index ΔCI -1.46, ΔR +0.22 minutes, Δα' -3.9°, ΔMA -9.3 mm) was recorded. No correlation between EPCR and CPB duration was recorded as well.
CPB is not associated with increase of EPCR - a novel endothelial marker - measured immediately after operation. We need further studies to explain mechanisms of endothelial protection in this clinical setting.