Depending on the fibrinolytic stage, DIC patients manifest clearly different clinical symptoms and laboratory findings. For many years, the diagnosis of DIC has been based on the criteria of the Ministry of Health, Labour and Welfare in Japan7
and the International Society on Thrombosis and Haemostasis (ISTH).10
In particular, the diagnostic criteria for DIC from the Ministry of Health, Labour and Welfare in Japan have shown high sensitivity and specificity in the detection of fibrinolysis hyperpermeability DIC in patients with solid tumors.11
Since DIC in the field of acute medicine progresses very quickly, as does the fibrinolytic inhibitor DIC in sepsis patients, it is necessary to make a diagnosis promptly without the need of special tests. In this context, the diagnostic criteria for acute DIC were reported by the JAAM in 2005.7
With regard to these diagnostic criteria for acute DIC, the relationship between the APACHE II score, the SOFA score, and the correlation with the outcome in septic shock cases have been reported.4
The JAAM DIC score serves as a useful, simple and easy tool to identify the severity of sepsis. When early diagnosis becomes possible by means of a simple, easy and prompt DIC score, then an effective post-diagnostic treatment method becomes indispensable.
APC was recommended in the Surviving Sepsis Campaign guidelines2
as a therapeutic medication for sepsis. APC inhibits excessive activation of the coagulation system, and it is believed to serve as an effective therapeutic medication for septic DIC. However, this treatment is not currently authorized in Japan, and the company that manufactured APC announced the withdrawal of its APC product from all markets following the results of a recent prospective study of recombinant APC.12
It has been confirmed that the AT-III activity level in the blood is significantly reduced in patients with septic DIC. As a result, double-blind tests have been performed in the belief that supplementation of AT-III in patients with septic DIC would improve the outcomes of sepsis.13
The main results included: positive outcomes were achieved in the AT-III administration group, although no significant differences were revealed by meta-analysis; a significantly shortened ICU stay; and an improved survival rate for patients who also experienced septic shock. In the present study, the patients received either an intravenous loading dose of 3000 IU AT-III followed by a maintenance dose of 1500 IU every 12 h for 5 days or equivalent amounts of placebo. The above treatment AT-III dose is similar to our manuscript treatment dose. A controlled double-blinded, randomized, multicenter study showed that high-dose (total dose, 24000 IU) AT-III replacement therapy in patients with sepsis and/or postsurgical complications decreased the risk of death.14
A systemic review of three randomized clinical trials showed that the combined odds ratio for short-term all-cause mortality in those who received antithrombin was 0.649.15
Another study showed that adjusted therapy with antithrombin was costly, but was associated with a reduction of total cost of care for patients with diffuse secondary peritonitis.16
In a previous paper, high-dose antithrombin without concomitant heparin in septic patients with DIC resulted in a significant mortality reduction, and it was concluded that the adapted ISTH DIC score could be used to identify patients with severe sepsis who would potentially benefit from high-dose antithrombin treatment.17
In the present retrospective study of 88 sepsis patients, significant improvements in outcomes were shown; the efficacy of antithrombin treatment was prominent particularly in DIC patients. Therefore, it is highly possible that AT-III improves the outcome of patients with septic DIC. Additionally, our study showed that the JAAM DIC score may identify patients with sepsis who could potentially benefit from normal-dose antithrombin treatment.
In conclusion, the findings of this study suggest that early administration of antithrombin might improve the outcomes of septic DIC patients who are classified according to the diagnostic criteria for acute DIC.