Haemodilution-induced profibrinolytic state is mitigated by fresh-frozen plasma: implications for early haemostatic intervention in massive haemorrhage

Background Fibrinolysis contributes to coagulopathy after major trauma and surgery. We hypothesized that progressive haemodilution is responsible, at least in part, for increased fibrinolytic tendency of blood clot. Methods The study was performed in two parts. First, whole blood (WB) samples collected from six healthy, consented volunteers were diluted in vitro with either saline or fresh-frozen plasma (FFP) to 40% and 15% of baseline. We quantified factor levels related to coagulation and fibrinolysis, and measured endogenous thrombin generation in undiluted control plasma samples and in samples diluted with saline or FFP. Additionally, thromboelastometry was used to assess susceptibility to fibrinolysis after adding tissue plasminogen activator in undiluted WB samples and in samples diluted with saline before and after substitution of fibrinogen or FFP. Secondly, as a model of in vivo haemodilution, we evaluated the same parameters before and after operation in nine consented patients undergoing off-pump coronary artery bypass surgery. Results The dilution with saline caused dose-dependent decreases in plasma levels of coagulation and antifibrinolytic factors, and in thrombin generation. In FFP-supplemented samples, factor levels and thrombin generation were maintained within normal ranges. Fibrinolytic tendency was significantly higher after haemodilution with saline independent of fibrinogen substitution compared with FFP. Similarly, increased tendency for fibrinolysis was also observed in the in vivo haemodilution. Conclusions We demonstrated in vitro and in vivo that progressive haemodilution decreases endogenous antifibrinolytic proteins including α2-antiplasmin and thrombin-activatable fibrinolysis inhibitor, resulting in increased fibrinolytic tendency. Therefore, early fluid replacement therapy with FFP might be advantageous after massive haemorrhag

Target Detection Performance Bounds in Compressive Imaging

This paper describes computationally efficient approaches and associated theoretical performance guarantees for the detection of known targets and anomalies from few projection measurements of the underlying signals. The proposed approaches accommodate signals of different strengths contaminated by a colored Gaussian background, and perform detection without reconstructing the underlying signals from the observations. The theoretical performance bounds of the target detector highlight fundamental tradeoffs among the number of measurements collected, amount of background signal present, signal-to-noise ratio, and similarity among potential targets coming from a known dictionary. The anomaly detector is designed to control the number of false discoveries. The proposed approach does not depend on a known sparse representation of targets; rather, the theoretical performance bounds exploit the structure of a known dictionary of targets and the distance preservation property of the measurement matrix. Simulation experiments illustrate the practicality and effectiveness of the proposed approaches.Comment: Submitted to the EURASIP Journal on Advances in Signal Processin

Multi-class transductive learning based on ℓ1 Relaxations of Cheeger Cut and Mumford-Shah-Potts Model

Recent advances in ℓ1 optimization for imaging problems provide promising tools to solve the fundamental high-dimensional data classification in machine learning. In this paper, we extend the main result of Szlam and Bresson (Proceedings of the 27th International Conference on Machine Learning, pp. 1039-1046, 2010), which introduced an exact ℓ1 relaxation of the Cheeger ratio cut problem for unsupervised data classification. The proposed extension deals with the multi-class transductive learning problem, which consists in learning several classes with a set of labels for each class. Learning several classes (i.e. more than two classes) simultaneously is generally a challenging problem, but the proposed method builds on strong results introduced in imaging to overcome the multi-class issue. Besides, the proposed multi-class transductive learning algorithms also benefit from recent fast ℓ1 solvers, specifically designed for the total variation norm, which plays a central role in our approach. Finally, experiments demonstrate that the proposed ℓ1 relaxation algorithms are more accurate and robust than standard ℓ2 relaxation methods s.a. spectral clustering, particularly when considering a very small number of labels for each class to be classified. For instance, the mean error of classification for the benchmark MNIST dataset of 60,000 data in \mathbb{R}^{784} using the proposed ℓ1 relaxation of the multi-class Cheeger cut is 2.4 % when only one label is considered for each class, while the error of classification for the ℓ2 relaxation method of spectral clustering is 24.7 %. © 2013 Springer Science+Business Media New York

Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model

Replacement of fibrinogen is presumably the key step in managing dilutional coagulopathy. We performed an in vitro study hypothesizing that there is a minimal fibrinogen concentration in diluted whole blood above which the rate of clot formation approaches normal. Blood samples from six healthy volunteers were diluted 1:5 v/v with saline keeping haematocrit at 24% using red cell concentrates. We measured coagulation factors and thrombin generation in plasma at baseline and after dilution. Thromboelastometry was used to evaluate (i) speed and quality of clot formation in diluted samples supplemented with fibrinogen 50-300 mg dl(-1) and (ii) clot resistance to fibrinolysis. Diluted and undiluted samples with no added fibrinogen served as controls. Coagulation parameters and platelets were reduced by 74-85% after dilution. Peak thrombin generation was reduced by 56%. Adding fibrinogen led to a concentration-dependent improvement of all thromboelastometric parameters. The half maximal effective concentration (EC50) for fibrinogen replacement in haemodiluted blood was calculated to be 125 mg dl(-1). Adding tissue plasminogen activator, 0.15 microg ml(-1), led to a decrease of clot firmness and lysis time. The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl(-1) as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy