Clinical Evaluation of Antithrombin III Concentrate (BI 6.013) for Disseminated Intravascular Coagulation in Obstetrics

Abstract

Antithrombin III (AT III) is known to be the most important inhibitor of serine protease in the coagulation system. In the presence of heparin, AT III is converted from its progressive activity state to an immediate activity state. In disseminated intravascular coagulation (DIC) in the field of obstetrics, the treatment has to be initiated very early. Heparin treatment, on the other hand, is critical since frequently postpartal or postoperative wound bleeding is present. We, therefore, established diagnostic criteria for the early diagnosis of DIC and investigated the clinical efficacy of a therapy with AT III in a well-controlled comparative study versus the injectable synthetic protease inhibitor FOY®. The results of the trial showed that the AT III group (92%; n = 24) was signifiacantly (p < 0.001) superior in clinical efficacy to the FOY group (60%; n = 15). No side effects whatsoever were observed after treatment with AT III concentrate (Behring Institute). From these results, it could be concluded that a single therapy with AT III concentrate can sufficiently control the symptoms of DIC in the filed of obstetrics without the risk of increased bleeding.

Antithrombin III (ATILL) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study

“…The number of eligible patients accepted in our ICUs in the study period correspond to the number of patients actually enrolled after the due exclusions. The ATIII dose was empirically fixed, from previously published clinical studies, and was sufficient to maintain the ATIII plasma concentration at 100% throughout the treatment period [2,10,11]. It should be noted that subsequent experimental [20,21] and clinical [22] studies stressed the importance of high-dose ATIII to maintain a supranormal level.…”

“…The concentration of ATIII in plasma is decreased in the conditions associated with disseminated intravascular coagulation (DIC), particularly in sepsis and shock [2][3][4][5]. Decreased plasma concentration of ATIII may be indicative of the role of DIC in the pathogenesis of multiple organ failure (MOF); it is a prognostic factor of poor outcome and correlates with survival [4,[6][7][8][9][10][11]. Two randomized studies addressed the use of ATIII concentrates in the treatment of DIC in sepsis and shock but did not include a placebo-control group.…”

Recent progress in the therapeutic management of pre-eclampsia

“…Previous publications confirmed the therapeutic efficacy of antithrombin in DIC [57], reducing mortality in patients with septic shock [58]. This evidence is the basis for considering antithrombin concentrates as an additional therapeutic modality [59,60].…”

Antithrombin III and local serum application: adjuvant therapy in peritonitis

“…Thus thrombin plays a major role in the development and maintenance of severe, acute inflammation. Moreover, several clinical studies have been published [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] exhibiting also some beneficial effects of lower AT III supplementation on haemostatic stabilization and reduction of organ failure in sepsis and DIC. Low AT III levels are correlated with higher mortality in septic patients [8], so that application of AT III concentrates seems to be a reasonable therapeutic approach.…”