Hirokatsu Hoshino

Sivelestat (Selective Neutrophil Elastase Inhibitor) Improves the Mortality Rate of Sepsis Associated With Both Acute Respiratory Distress Syndrome and Disseminated Intravascular Coagulation Patients

Neutrophil elastase plays an important role in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) in sepsis. Sivelestat is a selective neutrophil elastase inhibitor. It is possible that sivelestat improves the outcome of septic patients associated with ARDS and DIC. A retrospective data analysis of septic patients associated with ARDS and DIC was conducted to investigate the effects of sivelestat. Observational period was 5 days after admission to intensive care unit (ICU). The study included 167 septic patients associated with ARDS and DIC. Control group included 133 patients without sivelestat, and sivelestat group included 34 patients started to deadministered sivelestat on the admission to ICU. The lung injury scores and PaO2/FiO2 ratio of the sivelestat group were significantly more severe than those of the control group from days 1 to 4. On day 5, the lung injury score and PaO2/FiO2 ratio of the sivelestat group improved to the same levels of those of the control group. The DIC score of sivelestat group improved on day 3 in comparison to day 1, and those of control group remained unchanged until day 4. The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. A stepwise multiple logistic-regression analysis showed the sivelestat administration to be an independent predictor of survival of the septic patients associated with both ARDS and DIC. The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. In addition, sivelestat administration was found to be an independent predictor of survival of those patients.

A Prospective comparison of new Japanese criteria for disseminated intravascular coagulation: new Japanese criteria versus ISTH criteria.

In Japan, early diagnosis and early treatment of disseminated intravascular coagulation (DIC) based on the old Japanese criteria have greatly improved the outcomes of DIC patients with hematopoietic malignancy. However, the prognoses of critically ill patients with DIC have remained poor. To overcome this situation, new Japanese DIC criteria for critically ill patients were established in 2002. The new Japanese DIC criteria adopted a concept of coagulopathy associated with systemic inflammatory response syndrome. In the present study, we prospectively investigated the relationships between the new criteria and organ failure, prognosis, and other sets of DIC criteria. This study included 74 patients whose platelet counts were below 150 × 109/L. Daily DIC scores and sequential organ failure assessment scores were recorded from days 0 to 4 once the patient was included

Effects of antithrombin III in patients with disseminated intravascular coagulation diagnosed by newly developed diagnostic criteria for critical illness.

A study was conducted to test the hypotheses that antithrombin III (antithrombin) improves disseminated intravascular coagulation (DIC) when applied to DIC patients diagnosed by sensitive criteria and that the administration of high-dose antithrombin is a beneficial treatment for DIC. Twenty-three DIC patients diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC diagnostic criteria were treated with either high-dose (60 IU/kg/day) or low-dose (30 IU/kg/day) antithrombin concentrates for 3 days. The clinical conditions that cause DIC were restricted to systemic inflammatory response syndrome (SIRS) and sepsis. Data of antithrombin activity, platelet counts, coagulation and fibrinolytic markers, and DIC scores before antithrombin administration (day 0), on days 1 to 3, and on day 7 were retrospectively collected from computer-based records. Patients who met the JAAM DIC criteria were administered either high-dose (12 patients) or low-dose (11 patients) antithrombin. The patients’ backgrounds and antithrombin activity (high dose, 51.5 ± 14.5%; low dose, 62.6 ± 19.3%; P = .153) on day 0 were identical in the 2 groups. The JAAM DIC score and prothrombin time ratio on day 7 significantly improved when compared with those on day 0. However, mortality at 28 days as well as interaction within the antithrombin doses administered showed no difference. There were also no differences in the time course of the platelet counts, coagulation and fibrinolytic markers, and DIC scores in the 2 groups. The authors conclude that the effects of antithrombin on prognosis and coagulation and fibrinolytic parameters are independent of the doses administered in patients with SIRS/sepsis-associated DIC.

A Prospective Comparative Study of Three Sets of Criteria for Disseminated Intravascular Coagulation: ISTH Criteria vs Japanese Criteria

Clinical and laboratory criteria and a scoring system for disseminated intravascular coagulation (DIC) were recently published by the International Society on Thrombosis and Haemostasis (ISTH). In Japan, the DIC Diagnostic Standards published in 1988 have been widely used for more than 10 years. In a general intensive care unit, we prospectively compared the diagnostic properties of the overt DIC, nonovert DIC, and Japanese DIC criteria sets, and investigated the influences of each set on patient morbidity and mortality. Seventy-four patients with platelet counts below 150 × 109/L were included in this study. Blood samples were collected daily from day 0 to day 4 after inclusion in the study. The Japanese DIC included the overt DIC and both of these were included in the nonovert DIC. The Japanese DIC criteria diagnosed DIC earlier than the nonovert DIC criteria did (P = .020). The DIC patients diagnosed by the Japanese criteria and those diagnosed by the overt DIC criteria showed a higher incidence of multiple organ failure than those without DIC (P = .013 and P = .022, respectively). The Japanese and the nonovert DIC criteria tended to predict patient prognoses effectively. In conclusion, the Japanese and the nonovert DIC criteria are of value in predicting outcome. However, the nonovert DIC criteria take more time to diagnose DIC than the Japanese criteria do. A more precise clinical study is needed to determined appropriate specific criteria and cutoff points in the nonovert DIC criteria set.

The response of antithrombin III activity after supplementation decreases in proportion to the severity of sepsis and liver dysfunction

The decrease in the antithrombin III activity is thought to result from consumption by ongoing coagulation, degradation by neutrophil elastase, capillary leak syndrome, and impaired synthesis. A retrospective data analysis of patients with sepsis was conducted to investigate the response of antithrombin III activity after supplementation in patients with sepsis, and to determine what factors affect the response of antithrombin III activity. The study included 42 patients with sepsis, 75 patients with severe sepsis, and 65 patients with septic shock, who were administered antithrombin III. Antithrombin III activity, platelet counts, coagulation, and fibrinolytic markers were collected before administration and 24 h after the supplementation. In the patients with septic shock, the response of antithrombin III activity after supplementation was 0.37% ± 1.21%/IU per kg body weight, which was significantly lower in comparison with those in the patients with sepsis (1.81 ± 1.75; P < 0.001) or severe sepsis (1.36 ± 1.65; P < 0.001). The patients with liver dysfunction had significantly lower response to antithrombin III activity than that of the patients without liver dysfunction (P < 0.0001). A stepwise multiple linear regression analysis revealed that the severity of sepsis and liver function were independent predictors for the response to antithrombin III activity. These results suggest that the response to antithrombin III supplementation may be affected by both a systemic inflammation and impaired synthesis in patients with sepsis.