The glycocalyx is a carbohydrate-rich layer that lines the luminal side of the vascular endothelium. Its soluble components exist in a dynamic equilibrium with the bloodstream and play an important role in maintaining endothelial layer integrity. However, the glycocalyx can be easily damaged and is extremely vulnerable to insults from a variety of sources, including inflammation, trauma, haemorrhagic shock, hypovolemia and ischaemia-reperfusion. Damage to the glycocalyx commonly precedes further damage to the vascular endothelium. Preclinical research has identified a number of different factors capable of protecting or regenerating the glycocalyx. Initial investigations suggest that plasma may convey protective and regenerative effects. However, it remains unclear which exact components or properties of plasma are responsible for this protective effect. Studies have reported protective effects for several plasma proteins individually, including antithrombin, orosomucoid and albumin; the latter of which may be of particular interest, due to the high levels of albumin present in plasma. A further possibility is that plasma is simply a better intravascular volume expander than other resuscitation fluids. It has also been proposed that the protective effects are mediated indirectly via plasma resuscitation-induced changes in gene expression. Further work is needed to determine the importance of specific plasma proteins or other factors for glycocalyx protection, particularly in a clinical setting.

Cardiac surgery involving cardiopulmonary bypass (CPB) is often associated with important blood loss, allogeneic blood product usage, morbidity, and mortality. Coagulopathy during CPB is complex, and the current lack of uniformity for triggers and hemostatic agents has led to a wide variability in bleeding treatment. The aim of this review is to provide a simplified picture of the data available on patients’ coagulation status at the end of CPB in order to provide relevant information for the development of tailored transfusion algorithms. A nonsystematic literature review was carried out to identify changes in coagulation parameters during CPB. Both prothrombin time and activated partial thromboplastin time increased during CPB, by a median of 33.3% and 17.9%, respectively. However, there was marked variability across the published studies, indicating these tests may be unreliable for guiding hemostatic therapy. Some thrombin generation (TG) parameters were affected, as indicated by a median increase in TG lag time of 55.0%, a decrease in TG peak of 17.5%, and only a slight decrease in endogenous thrombin potential of 7%. The most affected parameters were fibrinogen levels and platelet count/function. Both plasma fibrinogen concentration and FIBTEM maximum clot firmness decreased during CPB (median change of 36.4% and 33.3%, respectively) as did platelet count (44.5%) and platelet component (34.2%). This review provides initial information regarding changes in coagulation parameters during CPB but highlights the variability in the reported results. Further studies are warranted to guide physicians on the parameters most appropriate to guide hemostatic therapy.

Tigecycline offers broad anti-bacterial coverage for critically ill patients with complicated infections. A described but less researched side effect is coagulopathy. The aim of this study was to test whether tigecycline interferes with fibrinogen polymerization by peripheral interactions. To study the effect of unmetabolized tigecycline, plasma of healthy volunteers were spiked with increasing concentrations of tigecycline. In a second experimental leg, immortalized human liver cells (HepG2) were treated with the same concentrations to test an inhibitory effect of hepatic tigecycline metabolites. Using standard coagulation tests, only the activated thromboplastin time in humane plasma was prolonged with increasing concentrations of tigecycline. Visualization of the fibrin network using confocal live microscopy demonstrated a qualitative difference in tigecycline treated experiments. Thrombelastometry and standard coagulation tests did not indicate an impairment of coagulation. Although the discrepancy between functional and immunologic fibrinogen levels increased in cell culture assays with tigecycline concentration, fibrinogen levels in spiked plasma samples did not show significant differences determined by functional versus immunologic methods. In our in vitro study, we excluded a direct effect of tigecycline in increasing concentrations on blood coagulation in healthy adults. Furthermore, we demonstrated a rapid loss of mitochondrial activity in hepatic cells with supra-therapeutic tigecycline dosages.

Tigecycline is a novel glycylcycline broad-spectrum antibiotic offering good coverage for critically ill patients experiencing complicated infections. A known side effect is a coagulation disorder with distinct hypofibrinogenemia. To date, the information on possible risk factors and outcomes is sparse. Therefore, the aim of this study is to examine the time course of fibrinogen level changes during tigecycline therapy in critically ill patients. Moreover, we sought to identify risk factors for coagulopathy and to report on clinically important outcomes. We retrospectively reviewed all intensive care patients admitted to our General and Surgical Intensive Care Unit receiving tigecycline between 2010 and 2018. A total of 130 patients were stratified into two groups based on the extent of fibrinogen decrease. Patients with a greater fibrinogen decrease received a higher dose, a longer treatment and more dose changes of tigecycline, respectively. In regard to the underlying pathology, these patients showed higher inflammation markers as well as a slightly reduced liver synthesis capacity. We, therefore, conclude that such a fibrinogen decrease may be based upon further impairment of liver synthesis during severe inflammatory states. To decrease the risk of bleeding, cautious monitoring of coagulation in critically ill patients treated with high-dose tigecycline is warranted.

The current study aims to evaluate whether prophylactic anticoagulation using argatroban or an increased dose of unfractionated heparin (UFH) is effective in achieving the targeted activated partial thromboplastin time (aPTT) of more than 45 s in critically ill heparin-resistant (HR) patients. Patients were randomized either to continue receiving an increased dose of UFH, or to be treated with argatroban. The endpoints were defined as achieving an aPTT target of more than 45 s at 7 h and 24 h. This clinical trial was registered on clinicaltrials.gov (NCT01734252) and on EudraCT (2012-000487-23). A total of 42 patients, 20 patients in the heparin and 22 in the argatroban group, were included. Of the patients with continued heparin treatment 55% achieved the target aPTT at 7 h, while only 40% of this group maintained the target aPTT after 24 h. Of the argatroban group 59% reached the target aPTT at 7 h, while at 24 h 86% of these patients maintained the targeted aPTT. Treatment success at 7 h did not differ between the groups (p = 0.1000), whereas at 24 h argatroban showed significantly greater efficacy (p = 0.0021) than did heparin. Argatroban also worked better in maintaining adequate anticoagulation in the further course of the study. There was no significant difference in the occurrence of bleeding or thromboembolic complications between the treatment groups. In the case of heparin-resistant critically ill patients, argatroban showed greater efficacy than did an increased dose of heparin in achieving adequate anticoagulation at 24 h and in maintaining the targeted aPTT goal throughout the treatment phase.

Intraoperative fluid therapy is regularly used in patients undergoing cardiac surgery procedures with cardiopulmonary bypass (CPB). Although fluid administration has several advantages, it unavoidably leads to hemodilution. The hemodilution may further influence the interpretation of concentration-based laboratory parameters like hemoglobin (Hgb), platelet count (PLT) or prothrombin time (PT). These all parameters are commonly used to guide blood product substitution. To assess the impact of dilution on these values, we performed a prospective observational study in 174 patients undergoing elective cardiac surgery. We calculated the total blood volume according to Nadler’s formula, and fluid therapy was correlated with a newly developed dilution coefficient formula at the end of CPB. Intravenously applied fluids were measured from the beginning of the anesthesia (baseline, T₀) and 15 min after the end of protamine infusion (end of CPB, T₁). The amount of the administered volume (crystalloids or colloids) was calculated according to the percentage of the intravascular fluid effect, and intraoperative diuresis was further subtracted. The median blood volume increased by 148% in all patients at T₁ compared to the calculated total blood volume at T₀. This led to a dilution-dependent decrease of 38% in all three parameters (Hgb 24%, corrCoeff = 0.53; PLT 41%, corrCoeff = 0.68; PT 44%, corrCoeff = 0.54). The dilution-correlated decrease was significant for all parameters (p < 0.001), and the effect was independent from the duration of CPB. We conclude that the presented calculation-based approach could provide important information regarding actual laboratory parameters and may help in the guidance of the blood product substitution and potential transfusion thresholds. Further research on the impact of dilution and related decision-making for blood product substitution, including its impact on morbidity and mortality, is warranted.