Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation
نویسندگان
چکیده
BACKGROUND Thrombomodulin alfa (TM-α, recombinant thrombomodulin) significantly improved disseminated intravascular coagulation (DIC) when compared with heparin therapy in a phase III study. Post-marketing surveillance of TM-α was performed to evaluate the effects and safety in patients with sepsis-induced DIC. METHODS From May 2008 to April 2010, a total of 1,787 patients with sepsis-induced DIC treated with TM-α were registered. DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) criteria. The DIC resolution and survival rates on day 28 after the last TM-α administration, and changes in DIC, systemic inflammatory response syndrome (SIRS), and sequential organ failure assessment (SOFA) scores and coagulation and inflammation markers were evaluated. RESULTS The most frequent underlying disease was infectious focus-unknown sepsis (29.8%). The mean ± SD values of age, dose, and the duration of TM-α administration were 64.7 ± 20.3 years, 297.3 ± 111.4 U/kg/day, and 5.6 ± 3.4 days, respectively. A total of 1,320 subjects (73.9%) received combined administration with other anticoagulants. Both coagulation and inflammation markers, such as fibrin/fibrinogen degradation products, prothrombin time ratio, thrombin-antithrombin complex, and C-reactive protein, as well as JAAM DIC, SIRS, and SOFA scores, significantly and simultaneously decreased after TM-α administration (p < 0.001). DIC resolution and 28-day survival rates were 44.4% and 66.0%, respectively. The 28-day survival rate decreased significantly according to the duration of DIC before TM-α administration (p < 0.001). Total adverse drug reactions (ADRs), bleeding ADRs, and serious bleeding adverse events occurred in 126 (7.1%), 98 (5.5%), and 121 (6.8%) subjects, respectively. On day 28, after the last TM-α administration available for an antibody test, only one patient was positive for anti-TM-α antibodies (0.11%). CONCLUSION Our results suggest that TM-α is most effective for treating patients with sepsis-induced DIC when administered within the first 3 days after diagnosis.
منابع مشابه
Plasma Fibrinogen and D-dimer in Children With Sepsis: A Single-center Experience
Background & Objectives: In sepsis, enhanced fibrin formation, impaired fibrin degradation, and intravascular fibrin deposition lead to a prothrombotic state. The current study aimed at measuring various coagulation parameters to predict an early marker for disseminated intravascular coagulation (DIC). Methods: The current prospective s...
متن کاملManagement of disseminated intravascular coagulation: current insights on antithrombin and thrombomodulin treatments
Sepsis and septic shock are frequently complicated by disseminated intravascular coagulation (DIC), which decreases the survival rate of patients with sepsis. In the past, large international randomized controlled trials (RCTs) using physiological anticoagulants for sepsis-induced DIC were not performed; however, RCTs have been conducted for sepsis and/or septic shock. In these trials, physiolo...
متن کاملPharmacokinetics of Recombinant Soluble Human Thrombomodulin in Subjects with Normal and Various Impaired Renal Function
Background: Non-clinical and clinical studies showed efficacy of thrombomodulin alfa for disseminated intravascular coagulation, and its potential efficacy for severe sepsis and coagulopathy. Thrombomodulin alfa is excreted primarily via the kidney and renal function is known to affect the clearance. However the dosing adjustments for patients with renal dysfunction were not warranted, except f...
متن کاملShort Communication Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin
متن کامل
Use of Recombinant Human Soluble Thrombomodulin in Patients with Sepsis-Induced Disseminated Intravascular Coagulation after Intestinal Perforation
BACKGROUND Anticoagulant therapy has been evaluated with respect to its potential usefulness in reducing the high mortality rates associated with severe sepsis, including sepsis-induced disseminated intravascular coagulation (DIC) after intestinal perforation. We examined the hypothesis that recombinant human soluble thrombomodulin (rhTM) is effective in the treatment of patients with septic sh...
متن کامل