Microparticles and Nucleosomes Are Released From Parenchymal Cells Destroyed After Injury in a Rat Model of Blunt Trauma.

We investigated the relationships between circulating procoagulants and trauma severity, including cellular destruction, and the effects of thrombin generation on procoagulants in a rat blunt trauma model. The rats were subjected to tumbling blunt trauma, where they were tumbled for 0, 250, 500, or 1000 revolutions. Creatine kinase, nucleosome, and microparticle plasma levels increased gradually with trauma severity. Strong interrelationships were observed among creatine kinase, nucleosome, and microparticle levels. Time to initiation of thrombin generation shortened with increasing trauma severity. In accordance with trauma severity, prothrombin activity decreased, but the thrombin generation ratio increased. Time to initiation of thrombin generation and the thrombin generation ratio correlated with creatine kinase levels. In an in vitro study, a homogenized muscle solution, which included massive nucleosomes and microparticles, showed accelerated thrombin generation of plasma from healthy subjects. Procoagulants, such as microparticles and nucleosomes, are released from destroyed parenchymal cells immediately after external traumatic force, activating the coagulation cascade. The procoagulants shorten the time to initiation of thrombin generation. Furthermore, although coagulation factors are consumed, the thrombin generation ratio increases.

Supernormal Antithrombin Activity Is an Independent Predictor of In-Hospital Mortality in Patients With Sepsis: A Retrospective Observational Study.

Supernormal antithrombin (AT) activity is rare in patients with sepsis. This study compared mortality rate of patients with sepsis and supernormal AT activity with that of other patients. This retrospective study included patients with sepsis from 42 intensive care units (ICUs) in Japan. Patients were included if their AT activity was measured on ICU admission, and if they did not receive AT concentrate. They were categorized into low, normal, and supernormal with respective AT activity of ≤70%, >70% to ≤100%, and >100%. The primary outcome was hospital in-patient mortality. Nonlinear regression analysis showed that mortality risk gradually increased with AT activity in the supernormal range, but without statistical significance. Survival rate was significantly lower in low (67%) and supernormal (57%) AT groups than in the normal AT group (79%; P < .001 and P = .008, respectively). After adjusting for disease severity and AT activity on day 2, supernormal AT activity was the only independent predictor of mortality. Sepsis with supernormal AT activity associated with high mortality, independent of disease severity, might be a predictor of in-hospital mortality.