Platelet Function in Stored Heparinised Autologous Blood Is Not Superior to in Patient Platelet Function during Routine Cardiopulmonary Bypass

Background: In cardiac surgery, cardiopulmonary bypass (CPB) and unfractionated heparin have negative effects on blood platelet function. In acute normovolemic haemodilution autologous unfractionated heparinised blood is stored ex-vivo and retransfused at the end of the procedure to reduce (allogeneic) transfusion requirements. In this observational study we assessed whether platelet function is better preserved in ex vivo stored autologous blood compared to platelet function in the patient during CPB. Methodology/Principal Finding: We measured platelet aggregation responses pre-CPB, 5 min after the start of CPB, at the end of CPB, and after unfractionated heparin reversal, using multiple electrode aggregometry (MultiplateH) with adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and ristocetin activated test cells. We compared blood samples taken from the patient with samples taken from 100 ml ex-vivo stored blood, which we took to mimick blood storage during normovolemic haemodilution. Platelet function declined both in ex-vivo stored blood as well as in blood taken from the patient. At the end of CPB there were no differences in platelet aggregation responses between samples from the ex vivo stored blood and the patient. Conclusion/Significance: Ex vivo preservation of autologous blood in unfractionated heparin does not seem to b

Are antifibrinolytic drugs equivalent in reducing blood loss and transfusion in cardiac surgery? A meta-analysis of randomized head-to-head trials

BACKGROUND: Aprotinin has been shown to be effective in reducing peri-operative blood loss and the need for re-operation due to continued bleeding in cardiac surgery. The lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are cheaper, but it is not known if they are as effective as aprotinin. METHODS: Studies were identified by searching electronic databases and bibliographies of published articles. Data from head-to-head trials were pooled using a conventional (Cochrane) meta-analytic approach and a Bayesian approach which estimated the posterior probability of TXA and EACA being equivalent to aprotinin; we used as a non-inferiority boundary a 20% increase in the rates of transfusion or re-operation because of bleeding. RESULTS: Peri-operative blood loss was significantly greater with TXA and EACA than with aprotinin: weighted mean differences were 106 mls (95% CI 37 to 227 mls) and 185 mls (95% CI 134 to 235 mls) respectively. The pooled relative risks (RR) of receiving an allogeneic red blood cell (RBC) transfusion with TXA and EACA, compared with aprotinin, were 1.08 (95% CI 0.88 to 1.32) and 1.14 (95% CI 0.84 to 1.55) respectively. The equivalent Bayesian posterior mean relative risks were 1.15 (95% Bayesian Credible Interval [BCI] 0.90 to 1.68) and 1.21 (95% BCI 0.79 to 1.82) respectively. For transfusion, using a 20% non-inferiority boundary, the posterior probabilities of TXA and EACA being non-inferior to aprotinin were 0.82 and 0.76 respectively. For re-operation the Cochrane RR for TXA vs. aprotinin was 0.98 (95% CI 0.51 to 1.88), compared with a posterior mean Bayesian RR of 0.63 (95% BCI 0.16 to 1.46). The posterior probability of TXA being non-inferior to aprotinin was 0.92, but this was sensitive to the inclusion of one small trial. CONCLUSION: The available data are conflicting regarding the equivalence of lysine analogues and aprotinin in reducing peri-operative bleeding, transfusion and the need for re-operation. Decisions are sensitive to the choice of clinical outcome and non-inferiority boundary. The data are an uncertain basis for replacing aprotinin with the cheaper lysine analogues in clinical practice. Progress has been hampered by small trials and failure to study clinically relevant outcomes

Aprotinin and Epsilon Aminocaproic Acid are Effective in Reducing Blood Loss After Primary Total Hip Arthroplasty - A Prospective Randomized Double-Blind Placebo-Controlled Study

Summary. A prospective randomized double-blind placebo-controlled study was undertaken to determine the efficacy and mechanism of action of two antifibrinolytic drugs aprotinin and epsilon aminocaproic acid (EACA) in reducing blood loss in primary unilateral total hip arthroplasty (THA). Aprotinin was administered as a bolus of 2 × 106 kallikrein inhibitor units (KIU) followed by 0.5 × 106 KIU h1 for 3 h, EACA was given as 10 g over 30 min followed by 5 g over 3 h. The median postoperative blood loss 24 h postoperatively was reduced from 450 mL in the placebo group to 180 mL for aprotinin (60% reduction, P < 0.001) and to 210 mL for EACA (53% reduction, P < 0.01). In this population, there was no reduction in the perioperative transfusion requirements. The mechanism of both drugs was independent of platelets as indicated by flow cytometric measurement of change of their expression of P-selectin, platelet–monocyte aggregates, V/Va and CD40 ligand. There were no thrombotic or infective complications and no adverse events were attributable to use of either drug. Infusion of either aprotinin or EACA at the doses described is a safe and effective means of reducing blood loss after THA. These therapies provide a means of reducing blood loss in THA patients

TraceLink: A model of amnesia and consolidation.

A connectionist model is presented, the TraceLink model, that implements an autonomous "off-line" consolidation process. The model consists of three subsystems: (1) a trace system(neocortex), (2) a link system (hippocampus and adjacent regions), and (3) a modulatory system (basal forebrain and other areas). The model is able to account for many of the characteristics of anterograde and retrograde amnesia,including Ribot gradients, transient global amnesia, patterns of shrinkage of retrograde amnesia, and correlations between anterograde and retrograde amnesia or the absence thereof (e.g., in isolated retrograde amnesia). In addition, it produces normal forgetting curves and can exhibit permastore. It also offers an explanation for the advantages of learning under high arousal for long-term retention

The utility of lung epithelium specific biomarkers in cardiac surgery:a comparison of biomarker profiles in on- and off-pump coronary bypass surgery

<p>Background: Despite continuous improvements in materials and perfusion techniques, cardiac surgery still causes lung injury and a delay of pulmonary recovery. Currently, there is no gold standard for quantifying cardiac surgery induced lung injury and dysfunction. Adding objective measures, such as plasma biomarkers, could be of great use here. In this study the utility of lung epithelium specific proteins as biomarkers for lung dysfunction was evaluated.</p><p>Methods: Serial measurements of plasma concentrations of Clara cell 16 kD (CC16) protein, Surfactant protein D (SP-D), Elastase and Myeloperoxidase were performed on blood samples from 40 patients who underwent coronary artery bypass grafting with cardiopulmonary bypass (CABG, n = 20) or without cardiopulmonary bypass (OPCAB, n = 20).</p><p>Results: The increase of SP-D and CC16 between pre-operative concentrations and concentrations at the end of cardiopulmonary bypass, correlated with the Aa-O-2 gradient at 1 hour on the ICU (R-s = 0.409, p = .016 and R-s = 0.343, p = .043, respectively). Furthermore, SP-D and CC16 were higher in CABG than in OPCAB at the end of surgery [8.96 vs. 4.91 ng/mL, p = .042 and 92 vs. 113%, p = .007, respectively]. After 24 h both biomarkers returned to their baseline values.</p><p>Conclusions: Our results show that increases in plasma of SP-D and CC16 correlate with clinical lung injury after coronary artery bypass surgery. Therefore, lung epithelium specific proteins seem to be a useful biomarker for measuring lung injury in the setting of cardiac surgery.</p>