Albumin-induced coagulopathy is less severe and more effectively reversed with fibrinogen concentrate than is synthetic colloid-induced coagulopathy

Abstract

Introduction Autophagy is well known as one of the biogenic responses against various stresses, which possesses the benefi cial roles for survival, but little is known about the dynamics and its signifi cance during the septic condition. We hypothesized that autophagy is induced during the septic condition, and contributes to protect from tissue damage which subsequently leads to organ dysfunction. We confi rm whether the autophagic process is accelerated or sustained in an acute phase of sepsis and we also determine its physiological role. Methods Sepsis was induced by cecal ligation and puncture (CLP) in mice. We examined the kinetics of autophagosome and auto lysosome formation which may explain the status of autophagy by western blotting, immunohistochemistry, and electron microscopy. To investigate a precise role of autophagy in CLP-induced sepsis, chloroquine, an autophagy inhibitor, was administered to the CLP-operated mice, and blood chemistry, pathology of the liver and survival were evaluated. Results Autophagy demonstrated by the ratio of LC3-II/LC3-I was induced over the time course up to 24 hours after CLP. The ratio was particularly increased in the liver, heart and spleen. Autophagosome formation became maximal at 6 hours and declined by 24 hours after CLP. Autolysosome formation as evaluated by both fusion of GFP-LC3 dots with LAMP1 immunohistochemistry and electron microscopy was also increased after the procedure. Furthermore, inhibition of autophagy by chloroquine during the CLP procedure resulted in elevation of serum AST levels, and signifi cantly increased mortality in mice. Conclusion Autophagy was induced in several organs over the time course of the CLP sepsis model and then the process was gradually completed to degradation of the components. Our data suggest autophagy plays a protective role in organ dysfunction in sepsis. P2Reversible depressive eff ect of TNFα on a model of isolated perfused rat heart BV Nguyen Introduction Acute myocardial depression in septic shock is common [1]. Myocardial depression is mediated by circulating depressant substances, which until now have been incompletely characterized [2].The aim of our study was to observe the eff ects of TNFα on the model of perfused rat heart. Methods After profound anesthesia with pentothal, the Wistar rats were killed by exsanguination. After sternotomy, the heart was taken and connected to the Langendorf column. The apex of the heart was hooked to a strength sensor. Biopac student laboratory software was used to record and analyse heart contractions. Contractions were recorded every 5 minutes during periods of 20 minutes. Control measurements were fi rst recorded. We measured four parameters: heart rate, contraction force, speeds of contraction and relaxation for control, during TNFα (20 ng/ml) exposure and after removal of TNFα. We express the variations of parameters as percentage of the control ± SEM. A paired t test was used to compare heart rate, contraction amplitude, speeds of contraction and relaxation with TNFα and ...

Fibrinogen and FXIII dose response effects on albumin-induced coagulopathy

“…The degree of impairment of ROTEM parameters induced by haemodilution with albumin is in agreement with an earlier study from our group [9]. It has previously been shown that addition of FXIII alone has no or little effect on ROTEM parameters following haemodilution with either Ringer's solution [17,18] or gelatin [21], and our results suggest that this is also the case for the natural colloid albumin.…”

“…However, colloids such as albumin, gelatin, hydroxyethyl starch (HES) and dextran confer advantages over crystalloids, including enhanced duration of haemodynamic effects and less capillary leakage [7,8]. A number of studies have shown that synthetic colloids including gelatin, hydroxyethyl starches and dextran, affect haemostatic parameters in whole blood viscoelastic tests (thromboelastography [ ]), to a greater extent than albumin [9][10][11][12][13][14]. Therefore, an initial volume substitution regime with 4-5% albumin, together with a restricted crystalloid regime, may be favourable.…”

“…Fibrinogen is the precursor of fibrin, which is crosslinked to form the basis of the clot, and is the first coagulation factor to fall to critical levels during massive bleeding [15,16]. Therapy with fibrinogen concentrate allows a precise dose of fibrinogen to be delivered quickly and in a small volume, and has been shown to effectively reverse dilutional coagulopathy in vitro following haemodilution with albumin [9], HES [3], dextran [3] or Ringer's acetate [17,18].…”

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation

“…This is a somewhat controversial result considering it has been suggested that albumin is no worse than saline, having less effect on hemostasis than other synthetic colloids. 35 However, a previous in vitro study which investigated the effect of dilution with albumin compared to starch in whole blood, similar to the present study, has also shown that albumin caused the greatest derangement in clotting. 7 Another study has also reported that albumin has a heparin-like effect on coagulation.…”

Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives: Chapter 5 Human Albumin - Revised

“…cardiac surgery patients with extracorporeal circulation) the application of albumin is possible since no substance-specific alterations regarding coagulation have been reported for human albumin use. However, the administration of large amounts of albumin can also cause a dilutional coagulopathy [116]. …”