Comparison of Protective Effects of Recombinant Antithrombin Gamma and Plasma-Derived Antithrombin on Sepsis-Induced Disseminated Intravascular Coagulation and Multiple Organ Failure

Abstract

In Japan, the dose of the new recombinant antithrombin III concentrate (rAT-gamma) is titrated according to patient body weight (BW), while conventional plasma-derived antithrombin concentrates (AT) are administered as a fixed dose. Therefore, it is anticipated that rAT-gamma could produce better treatment effects than AT. The aim of this study was to compare the organ protective effects of doses of rAT-gamma and AT administered in clinical practice for septic disseminated intravascular coagulation (DIC) and multiple organ failure. This study was performed at a single university hospital in Japan. A total of 49 patients with antithrombin deficiency secondary to septic DIC who were administered either rAT-gamma (n = 26) or AT (n = 23) were retrospectively analyzed to assess the dose of supplemental antithrombin concentrates, plasma antithrombin activity, Japanese Association for Acute Medicine (JAAM)-DIC score, and modified Sequential Organ Failure Assessment (SOFA) score on days 0, 3 and 6. The AT-equivalent dose per kg BW of rAT-gamma (equal to the initial rAT-gamma dose per kg BW divided by 1.2) was significantly higher than the dose per kg BW of AT (AT 23.4 ± 5.1 vs. rAT 28.9 ± 3.9 IU/kg/day; P < 0.001). Consequently, serial increases in plasma antithrombin levels occurred more rapidly in the rAT-gamma group (P = 0.036). JAAM DIC and modified SOFA scores revealed significantly greater improvement in the rAT versus the AT group (JAAM DIC score: P = 0.042, mSOFA score: P = 0.005). The results of this study suggest that AT supplementation adjusted for patient BW might further improve septic DIC and multiple organ failure.

Keywords: antithrombin III; disseminated intravascular coagulation; recombinant antithrombin gamma; sepsis; sequential organ failure assessment score.

Figure 1.

Patient enrollment in this study. AT: antithrombin, AT group: plasma-derived antithrombin group, rAT group: recombinant antithrombin gamma group, DIC: disseminated intravascular coagulation.

Figure 2.

Changes in plasma antithrombin levels during the observation period. Baseline plasma AT levels were approximately 40% in the 2 groups. However, the increment with supplementation in the rAT group was significantly larger than that in the AT group (P = 0.036), as was the maximum plasma AT level and the area under the curve of plasma AT level from day 0 to day 4 (P = 0.022, P = 0.003, respectively). AT: antithrombin, AT group: plasma-derived antithrombin group, rAT group: recombinant antithrombin gamma group.

Figure 3.

Changes in mSOFA score (A) and JAAM-DIC score (B). The baseline values of both scores were similar between the AT and rAT groups. However, the rAT group achieved significantly larger decrements in both mSOFA and JAAM-DIC scores than the AT group (P = 0.005 and P = 0.042, respectively). *P < 0.01 versus each score in the rAT group on days 3 and 6. #P < 0.05 versus the mSOFA score in the AT group on day 0. mSOFA: modified sequential organ failure assessment, JAAM-DIC: Japanese Association for Acute Medicine-disseminated intravascular coagulation, AT group: plasma-derived antithrombin group, rAT group: recombinant antithrombin gamma group.

Figure 4.

DIC recovery rate. Although the difference between the 2 groups was not statistically significant, the recovery rate in the rAT group was almost twice that in the AT group on each day. The results are presented as the DIC recovery rate. AT group: plasma-derived antithrombin group, rAT group: recombinant antithrombin gamma group.