Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
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Blood Coagul. Fibrinolysis · Mar 2015
Effects of gabexate mesilate on coagulopathy and organ dysfunction in rats with endotoxemia: a potential use of thrombelastography in endotoxin-induced sepsis.
Sepsis and its associated multiple organ failure are related to high mortality in critical patients. Several studies have reported that gabexate mesilate, a synthetic inhibitor of trypsin-like serine protease, protects tissues/organs against injury in the models of endotoxemia. The aim of this study was to examine whether gabexate mesilate could attenuate coagulopathy and organ dysfunction in lipopolysaccharide (LPS)-induced sepsis model by using thrombelastography (TEG). ⋯ In addition, TEG parameters correlated with tissue and liver injury in the late phase of endotoxemia. In particular, a strong negative correlation between maximal amplitude at 4 h and Ln (lactate dehydrogenase) at 6 h after LPS infusion was noted (r = -0.752, P < 0.001, R = 0.566). These results indicate that beneficial effects of anticoagulants (e.g. gabexate mesilate) in endotoxemia could be monitored by TEG per se.
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Blood Coagul. Fibrinolysis · Mar 2015
Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy.
Acute traumatic coagulopathy (ATC) may trigger sympathoadrenal activation associated with endothelial damage and coagulation disturbances. Overexcitation of sympathetic nerve in this state would disrupt sympathetic-vagal balance, leading to autonomic nervous system dysfunction. The aim of this study was to evaluate the autonomic function in ATC and its influence on inflammation, endothelial and coagulation activation. ⋯ These data indicated that autonomic dysfunction in ATC involves both sympathetic activation and parasympathetic inhibition. Moreover, sympathectomy yielded anti-inflammatory, antifibrinolysis and endothelial protective effects in rats with ATC. The role of autonomic neuropathy in ATC should be explored further.
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Blood Coagul. Fibrinolysis · Dec 2014
A simple method to identify patients on long-term warfarin who may derive the most benefit from new oral anticoagulants.
In many countries, new oral anticoagulants are only covered for patients with suboptimal anticoagulation control on vitamin K antagonists (VKAs). The quality of VKA management is often reported using the time in therapeutic range (TTR). We sought to predict a TTR 65% or less using a surrogate measure [number of changes in VKA dose and number of international normalized ratio (INR) tests] that could be easily determined by primary care physicians. ⋯ The sensitivity to identify patients with TTR 65% or less was 87% and the specificity was 63%. The number of dose changes and the number of INR tests might be used as indicators of TTR; they could offer a simple way for clinicians to identify patients who are good candidates for the new oral anticoagulants. However, external validation studies in different clinical settings are needed to confirm these findings.
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Blood Coagul. Fibrinolysis · Dec 2014
Impact of withdrawing antithrombin III administration from management of septic patients with or without disseminated intravascular coagulation.
Antithrombin III (ATIII) of low doses (1500-3000 units per day for 3-5 days) has been used for treatment of disseminated intravascular coagulation (DIC) for decades in Japan. In this study, we have examined the impact of ATIII practice change on outcome in critically ill patients with sepsis and DIC. From April 2005 to September 2008, all septic patients admitted to our ICU were divided into two groups: before withdrawing ATIII (period 1) and after withdrawing ATIII (period 2). ⋯ There was no difference between the two DIC groups for platelet counts, Sepsis-related organ failure assessment scores and DIC score at day 1 and also day 4. Although not significant, hospital mortality tended lower in the period 2. This study found that withdrawing ATIII administration from management of septic patients with or without DIC did not influence outcome.
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Blood Coagul. Fibrinolysis · Dec 2014
Effects of a plasma-derived C1 esterase inhibitor on hemostatic activation, clot formation, and thrombin generation.
Hereditary angioedema (HAE) is a rare, autosomal dominant disease in which C1 esterase inhibitor (C1 INH) is deficient or dysfunctional. Package inserts for nanofiltered C1 esterase inhibitor (C1 INH-nf) products contain warnings about thrombotic events. The objective of this study was to evaluate the effect of C1 INH-nf on hemostatic activation, clot formation, and thrombin generation. ⋯ C1 INH-nf 2.8 and 7.0 U/ml concentrations had a statistically significant anticoagulant effect on maximum clot firmness (P < 0.05 for all comparisons of C1 INH-nf versus negative control), with a magnitude similar to that observed with desirudin. C1 INH-nf had no effect on thrombin generation lag time, peak thrombin generation, or thrombin generation rate, regardless of the final concentration or activating reagent used (P < 0.05 for all comparisons of C1 INH-nf versus negative controls). We found no evidence of a procoagulant effect of C1 INH-nf when studied ex vivo at concentrations up to 10-fold higher than those achieved with clinical dosing in patients with HAE.