Antithrombin III in patients with severe sepsis

Abstract

The administration of AT III was safe and well-tolerated. It was followed by a 39 % reduction in 30-day all-cause mortality (NS). The reduction in mortality was accompanied by a considerably shorter stay in the ICU. Patients treated with AT III exhibited a better performance in overall severity of illness and organ failure scores (Acute Physiology and Chronic Health Evaluation II, multiple organ failure, organ system failure), which was noticeable soon after initiation of treatment. Patients treated with AT III demonstrated a better resolution of pre-existing organ failures and a lower incidence of new organ failures during the observation period. A meta-analysis comprising this and two other double-blind, placebo-controlled trials with AT III with a total of 122 patients suffering from severe sepsis confirms the positive trend. The results of the meta-analysis demonstrate a 22.9 % reduction in 30-day all-cause mortality in patients treated with AT III. Although still too small to be confirmative, the meta-analysis clearly points to the fact that a sufficiently powered phase III trial is warranted to prove whether AT III has a beneficial role in the treatment of severe sepsis.

A summary of the Japan septic disseminated intravascular coagulation study

“…However, in sepsis‐induced DIC, a decrease in AT activity is frequently observed27, 28, 29, 30 and is associated with high mortality rates 31, 32. Several RCTs to investigate the effects of high‐dose AT administration in patients with sepsis have been carried out 4, 33, 34, 35, 36. Although some RCTs indicated benefits of high‐dose AT administration in patients with sepsis,33, 34, 35 a large RCT (the KyberSept trial) failed to show any survival benefits 4.…”

“…Several RCTs to investigate the effects of high‐dose AT administration in patients with sepsis have been carried out 4, 33, 34, 35, 36. Although some RCTs indicated benefits of high‐dose AT administration in patients with sepsis,33, 34, 35 a large RCT (the KyberSept trial) failed to show any survival benefits 4. However, a subgroup analysis of the KyberSept trial indicated that AT administration significantly improved survival rates in patients with sepsis‐induced DIC 9…”

Pemberian Antitrombin III pada Anak dengan Keadaan Sepsis

“…Ketiga uji klinis menggunakan dosis AT III yang berbeda-beda. Dua uji klinis menggunakan dosis AT III yang rendah, yaitu uji klinis Eisele 4 dan uji klinis Schuster 4 sedangkan uji klinis lainnya, yaitu studi Fourrier dkk, 4 menggunakan dosis AT III yang tinggi.…”

“…Terjadinya KID dimulai dengan sitokin mengaktivasi jalur koagulasi secara sistemik sehingga terjadi consumptive coagulopati. 4 Usaha untuk menghentikan proses KID dengan suplementasi AT III sudah dimulai sejak sekitar tahun 1990 namun masih diperdebatkan baik dalam hal luaran dari penggunaan suplementasi tersebut, dosis penggunaan, interaksi dengan heparin, dan efek samping penggunaan. Antithrombin III adalah suatu glikoprotein rantai tunggal yang diproduksi oleh hati dan termasuk dalam serine protease inhibitor (SERPIN) superfamily.…”

Influence of Antithrombin III on Coagulation and Inflammation in Porcine Septic Shock

“…23 A recently published paper on the meta-analysis of ATIII in severe sepsis demonstrated a clear trend towards increased survival. 24 However, some authors suggest that ATIII might have antiinflammatory as well as anti-DIC activity. 25 In the present study we induced a sepsis by the infusion of Salmonella abortus equi lipopolysaccharide into pigs; the development of systemic inflammation, coagulation activation and hemodynamic changes was followed over time.…”